5-aminosalicylic acid(5-ASA) is drug of choice for the treatment of ulcerative colitis(UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mecha...5-aminosalicylic acid(5-ASA) is drug of choice for the treatment of ulcerative colitis(UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced UC. A total of 60 rats were divided into sham operation group(receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group(a release agent of mesalazine used as positive control) and oral 5-ASA group(n=12 each). Different treatments were administered 1 day after UC induction. The normal saline(2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group(7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa(7.5 g/L, twice per day, 100 mg/kg) and 5-ASA(7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography(HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.展开更多
Objective: To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides(APS) tre...Objective: To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides(APS) treatment. Methods: Thirty-two male specific pathogen free Spragne-Dawley rats were randomly equally assigned to four groups: control, TNBS, APS and prednisone groups. Experimental colitis was induced by enema administration of TNBS. Then rats were treated with APS(0.5 g·kg^(-1)·day^(-1), once daily) or prednisone(1.0 mg·kg^(-1)·day^(-1), once daily) by gavage for 14 days. Macroscopic lesion and histological damage were determined, and activity of myeloperoxidase(MPO) was measured in the colonic tissues. Expressions of T-box expressed in T-cells(T-bet) and GATA-binding protein-3(GATA-3) were determined by immunohistochemistry analysis and western blot. Results: Both macroscopic lesion and histological colonic damage induced by TNBS were reduced by APS and prednisone treatment. These were accompanied by significant attenuation of MPO activity(P=0.03). TNBS intervention enhanced the expression of both GATA-3 and T-bet, but the expression of T-bet was significantly enhanced than that of GATA-3, resulting in significant reduction of GATA-3/T-bet ratio(P=0.025). APS administration enhanced the expression of T-bet(P=0.04) and GATA-3(P=0.019) in comparison to TNBS group, and resulting in an up-regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions; however it also resulted in up-regulation of the GATA-3/T-bet ratio. Conclusions: These results demonstrated that APS exerted a beneficial immune regulatory effect on experimental colitis. It promoted the expression of T helper cell 1(Th1) and T helper cell 2(Th2) specific transcription factors but ultimately favor a shift toward Th2 phenotype, suggesting that APS possessed therapeutic potential in experimental colitis.展开更多
Nano titania-supported sulfonic acid(n-TSA) has found to be a highly efficient, eco-friendly and recyclable heterogeneous nanocatalyst for the solvent-free synthesis of 2,4,6-triarylpyridines through one-pot three-c...Nano titania-supported sulfonic acid(n-TSA) has found to be a highly efficient, eco-friendly and recyclable heterogeneous nanocatalyst for the solvent-free synthesis of 2,4,6-triarylpyridines through one-pot three-component reaction of acetophenones, aryl aldehydes and ammonium acetate. This reported method illustrates several advantages such as environmental friendliness reaction conditions,simplicity, short reaction time, easy work up, reusability of catalyst and high yields of the products. One new compound is reported too. Furthermore, the catalyst could be recycled after a simple work-up, and reused at least six times without substantial reduction in its catalytic activity.展开更多
We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid(HMW HA) could rescue trinitrobenzene sulfonic acid(TNBS)-induced colitis through Toll-like receptor 4(TLR4) signal.C3H/HeN mice ...We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid(HMW HA) could rescue trinitrobenzene sulfonic acid(TNBS)-induced colitis through Toll-like receptor 4(TLR4) signal.C3H/HeN mice and C3H/HeJ mice were used.Mice were divided into four groups:control,50% ethanol treatment group,TNBS treatment group,and TNBS plus HA treatment group.The weight changes,clinical scores,macroscopic scores,and histological scores were recorded.Cyclooxygenase 2(Cox-2) and prostaglandin E 2(PGE 2) expressions were measured both in colons and peritoneal macrophages from these mice.HA was a rescue therapy for the colitis induced by TNBS only in C3H/HeN mice.The clinical score,macroscopic score,and histological score were much lower in C3H/HeN mice receiving TNBS plus HA treatment.Cox-2 and PGE 2 expressions only increased in C3H/HeN mice.These Cox-2 expressing cells were macrophages.HA can also promote the production of Cox-2 and PGE 2 in peritoneal macrophages from C3H/HeN mice.Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE 2 expressions in a TLR4-dependent way.Macrophages may be the effector cells of HMW HA.展开更多
以硒为催化剂、CO为还原剂、水为氢源、无机弱碱为助催化剂、N,N-二甲基甲酰胺(DMF)作溶剂,常压下将3,5-二硝基-2,4,6-三甲基苯磺酸还原为3-硝基-5-氨基-2,4,6-三甲基苯磺酸。最优反应条件为:3,5-二硝基-2,4,6-三甲基苯磺酸1. 45 g (5 m...以硒为催化剂、CO为还原剂、水为氢源、无机弱碱为助催化剂、N,N-二甲基甲酰胺(DMF)作溶剂,常压下将3,5-二硝基-2,4,6-三甲基苯磺酸还原为3-硝基-5-氨基-2,4,6-三甲基苯磺酸。最优反应条件为:3,5-二硝基-2,4,6-三甲基苯磺酸1. 45 g (5 mmol),无水醋酸钠0. 492 g (6 mmol),DMF 30 m L,水3 m L,在95℃下回流反应5h。产物纯度可达87. 92%。展开更多
AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both ...AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250-300 g, were employed in the present study. The rat colitis models were induced by 2, 4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg in 50% ethanol. The experimental animals were randomly divided into dexamethasone (DX) treatment, CTG treatment, and model control groups, which were intracolicly treated daily with DX (0.2 mg/kg), CTG at doses of 2.9, 5.7 and 11.4 g crude drug/kg, and the equal amount of saline respectively from 6 h following induction of the colitis in rats inflicted with TNBS to the end of study. A normal control group of rats treated without TNBS but saline enema was also included in the study. After 3 wk of treatment, the animals were assessed for colonal inflammatory and ulcerative responses with respect to mortality, frequency of diarrhea, histology and myeloperoxidase activity (MPO).RESULTS: The therapeutic effect of CTG on ulcerative colitis (UC) was better than DX. CTG effectively inhibited the activity of granulocytes, macrophages and monocytes in a dosedependent manner. Also it reduced MPO and formation of inflammation in colonic mucosal tissue. Furthermore, administration of CTG significantly prevented body mass loss and death, and decreased frequency of diarrhea in UC rats, when compared with the model control group rats.CONCLUSION: CTG would prove to be an ideal drug for chronic UC, and is warranted to be studied further.展开更多
AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following c...AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.展开更多
Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial ceils of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-...Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial ceils of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis, and to investigate the possible mechanism of SQR in regulating intestinal dynamics. Methods Sixty rats were randomly divided into normal control, model Ⅰ , model Ⅱ, mesalazine, and high-dose, and low-dose SQR groups with 10 rats in each group. TNBS (10 mg) dissolved in 50% ethanol was instilled into the lumen of the rat colon of the latter five groups to induce colitis. On the 4th day after administration of TNBS, each treatment group was administered one of the following formulations by enteroclysis gavage once a day for 7 days: 600 mg·kg^-1·d^-1 mesalazine, 2.4g^-1·d^-1 SQR, and 1.2g^-1·d^-1 SQR. Model Ⅱ rats received normal saline solution. After 7 days colonic samples were collected. While the colonic samples of model I group were collected on the 3rd day after TNBS administered. Ultrastructure of ICC in the damaged colonic tissues was observed with transmission electron microscope. Expression of c-kit protein in colonic tissue was determined by immunohistochemical staining and Western blot. Results The ultrastructure of colonic ICC in the rat model of TNBS-induced colitis showed a severe injury, and administration of SQR or mesalazine reduced the severity of injury. Similarly, the expression of c-kit protein of TNBS-induced colitis rat model was significantly decreased compared with the normal control group (P〈0.05). Treatment with SQR or mesalazine significantly increased the expression of c-kit protein compared with the administration of control formulations (P〈0.05), especially the high-dose SQR group. Conclusion SQR could alleviate and repair the injured ICC, and improve its quantity, which might be involved in regulating intestinal motility.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81072431)the Innova-tion Foundation of Huazhong University of Science and Tech-nology(No.2010MS027)
文摘5-aminosalicylic acid(5-ASA) is drug of choice for the treatment of ulcerative colitis(UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced UC. A total of 60 rats were divided into sham operation group(receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group(a release agent of mesalazine used as positive control) and oral 5-ASA group(n=12 each). Different treatments were administered 1 day after UC induction. The normal saline(2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group(7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa(7.5 g/L, twice per day, 100 mg/kg) and 5-ASA(7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography(HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.
基金Supported by Doctoral Fund of Ministry of Education of China
文摘Objective: To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides(APS) treatment. Methods: Thirty-two male specific pathogen free Spragne-Dawley rats were randomly equally assigned to four groups: control, TNBS, APS and prednisone groups. Experimental colitis was induced by enema administration of TNBS. Then rats were treated with APS(0.5 g·kg^(-1)·day^(-1), once daily) or prednisone(1.0 mg·kg^(-1)·day^(-1), once daily) by gavage for 14 days. Macroscopic lesion and histological damage were determined, and activity of myeloperoxidase(MPO) was measured in the colonic tissues. Expressions of T-box expressed in T-cells(T-bet) and GATA-binding protein-3(GATA-3) were determined by immunohistochemistry analysis and western blot. Results: Both macroscopic lesion and histological colonic damage induced by TNBS were reduced by APS and prednisone treatment. These were accompanied by significant attenuation of MPO activity(P=0.03). TNBS intervention enhanced the expression of both GATA-3 and T-bet, but the expression of T-bet was significantly enhanced than that of GATA-3, resulting in significant reduction of GATA-3/T-bet ratio(P=0.025). APS administration enhanced the expression of T-bet(P=0.04) and GATA-3(P=0.019) in comparison to TNBS group, and resulting in an up-regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions; however it also resulted in up-regulation of the GATA-3/T-bet ratio. Conclusions: These results demonstrated that APS exerted a beneficial immune regulatory effect on experimental colitis. It promoted the expression of T helper cell 1(Th1) and T helper cell 2(Th2) specific transcription factors but ultimately favor a shift toward Th2 phenotype, suggesting that APS possessed therapeutic potential in experimental colitis.
基金the Faculty of Chemistry of Semnan University for supporting this work
文摘Nano titania-supported sulfonic acid(n-TSA) has found to be a highly efficient, eco-friendly and recyclable heterogeneous nanocatalyst for the solvent-free synthesis of 2,4,6-triarylpyridines through one-pot three-component reaction of acetophenones, aryl aldehydes and ammonium acetate. This reported method illustrates several advantages such as environmental friendliness reaction conditions,simplicity, short reaction time, easy work up, reusability of catalyst and high yields of the products. One new compound is reported too. Furthermore, the catalyst could be recycled after a simple work-up, and reused at least six times without substantial reduction in its catalytic activity.
基金Project (No. C140404) supported by National Natural Science Foundation of China
文摘We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid(HMW HA) could rescue trinitrobenzene sulfonic acid(TNBS)-induced colitis through Toll-like receptor 4(TLR4) signal.C3H/HeN mice and C3H/HeJ mice were used.Mice were divided into four groups:control,50% ethanol treatment group,TNBS treatment group,and TNBS plus HA treatment group.The weight changes,clinical scores,macroscopic scores,and histological scores were recorded.Cyclooxygenase 2(Cox-2) and prostaglandin E 2(PGE 2) expressions were measured both in colons and peritoneal macrophages from these mice.HA was a rescue therapy for the colitis induced by TNBS only in C3H/HeN mice.The clinical score,macroscopic score,and histological score were much lower in C3H/HeN mice receiving TNBS plus HA treatment.Cox-2 and PGE 2 expressions only increased in C3H/HeN mice.These Cox-2 expressing cells were macrophages.HA can also promote the production of Cox-2 and PGE 2 in peritoneal macrophages from C3H/HeN mice.Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE 2 expressions in a TLR4-dependent way.Macrophages may be the effector cells of HMW HA.
文摘以硒为催化剂、CO为还原剂、水为氢源、无机弱碱为助催化剂、N,N-二甲基甲酰胺(DMF)作溶剂,常压下将3,5-二硝基-2,4,6-三甲基苯磺酸还原为3-硝基-5-氨基-2,4,6-三甲基苯磺酸。最优反应条件为:3,5-二硝基-2,4,6-三甲基苯磺酸1. 45 g (5 mmol),无水醋酸钠0. 492 g (6 mmol),DMF 30 m L,水3 m L,在95℃下回流反应5h。产物纯度可达87. 92%。
基金Supported by the Science and Technology Development Fund of Shanghai,No.03DZ19531
文摘AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250-300 g, were employed in the present study. The rat colitis models were induced by 2, 4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg in 50% ethanol. The experimental animals were randomly divided into dexamethasone (DX) treatment, CTG treatment, and model control groups, which were intracolicly treated daily with DX (0.2 mg/kg), CTG at doses of 2.9, 5.7 and 11.4 g crude drug/kg, and the equal amount of saline respectively from 6 h following induction of the colitis in rats inflicted with TNBS to the end of study. A normal control group of rats treated without TNBS but saline enema was also included in the study. After 3 wk of treatment, the animals were assessed for colonal inflammatory and ulcerative responses with respect to mortality, frequency of diarrhea, histology and myeloperoxidase activity (MPO).RESULTS: The therapeutic effect of CTG on ulcerative colitis (UC) was better than DX. CTG effectively inhibited the activity of granulocytes, macrophages and monocytes in a dosedependent manner. Also it reduced MPO and formation of inflammation in colonic mucosal tissue. Furthermore, administration of CTG significantly prevented body mass loss and death, and decreased frequency of diarrhea in UC rats, when compared with the model control group rats.CONCLUSION: CTG would prove to be an ideal drug for chronic UC, and is warranted to be studied further.
基金Supported by Hong Kong Jockey Club Institute of Chinese Medicine,No.JCICM-4-07
文摘AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.
基金Supported by the Shanghai Committee of Science and Technology Foundation for Research Discipline Project (06411941)the Shanghai Leading Academic Discipline Project (J50305)
文摘Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial ceils of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis, and to investigate the possible mechanism of SQR in regulating intestinal dynamics. Methods Sixty rats were randomly divided into normal control, model Ⅰ , model Ⅱ, mesalazine, and high-dose, and low-dose SQR groups with 10 rats in each group. TNBS (10 mg) dissolved in 50% ethanol was instilled into the lumen of the rat colon of the latter five groups to induce colitis. On the 4th day after administration of TNBS, each treatment group was administered one of the following formulations by enteroclysis gavage once a day for 7 days: 600 mg·kg^-1·d^-1 mesalazine, 2.4g^-1·d^-1 SQR, and 1.2g^-1·d^-1 SQR. Model Ⅱ rats received normal saline solution. After 7 days colonic samples were collected. While the colonic samples of model I group were collected on the 3rd day after TNBS administered. Ultrastructure of ICC in the damaged colonic tissues was observed with transmission electron microscope. Expression of c-kit protein in colonic tissue was determined by immunohistochemical staining and Western blot. Results The ultrastructure of colonic ICC in the rat model of TNBS-induced colitis showed a severe injury, and administration of SQR or mesalazine reduced the severity of injury. Similarly, the expression of c-kit protein of TNBS-induced colitis rat model was significantly decreased compared with the normal control group (P〈0.05). Treatment with SQR or mesalazine significantly increased the expression of c-kit protein compared with the administration of control formulations (P〈0.05), especially the high-dose SQR group. Conclusion SQR could alleviate and repair the injured ICC, and improve its quantity, which might be involved in regulating intestinal motility.