Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-...Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.展开更多
Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD patt...Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.展开更多
Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic an...Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.展开更多
using a WZD—1 microcirculation microscope,we observed the tongue tipand nail-bed microcirculation of uremic patients with deficiency of kidney-yangbefore and after blood dialysis.The results showed that the pathologi...using a WZD—1 microcirculation microscope,we observed the tongue tipand nail-bed microcirculation of uremic patients with deficiency of kidney-yangbefore and after blood dialysis.The results showed that the pathological basis ofuremia with deficiency of kidney-yang may be microcirculation disturbance,in-crease of metabolites and water retention.The effusion from capillary loops intongue tip may be one of the pathogenetic factors of a swollen and jaggedtongue.The flow rate of blood in capillary loops in the nail-bed was apparentlyabnormal and markedly improved after blood dialysis.The weighted integral ofnail-bed microcirculation decreased from moderately abnormal (4.99±1.52) toapproximately normal (1.98±0.97) (P【0.01).Microcirculation seems to be a sensi-tive criterion for reflecting the pathologic changes of uremia with deficiency ofkidney-yang.展开更多
OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxi...OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81673996,81904220)the Jiangmen Association for Science and Technology-Youth science and technology talent lifting project(Grant No.2022-2023).
文摘Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang deficiency.Methods:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical staining.The expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantly,and the expression of cGMP increased in the osteoporosis with kidney-yang deficiency group.Moreover,both YGW and ALN effectively improved the symptoms of osteoporosis,including the injury of bone trabeculae and growth plates,as well as the expression of bone metabolism-related indicators.However,unlike ALN,YGW simultaneously ameliorated the expression of key indicators of kidney-yang deficiency and prevented weight loss in rats.In addition,YGW caused no obvious damage to the liver,spleen,or kidney,whereas ALN led to liver cirrhosis.Conclusion:The results reveal that YGW plays a crucial part in osteoporosis with kidney-yang deficiency,increases bone mineral density,and improves bone metabolism indicators,and is safe and efficient for the efficacy of osteoporosis with kidney-yang deficiency.YGW might have a better therapeutic effect on osteoporosis in patients with kidney-yang deficiency.Therefore,alendronate should be used cautiously in patients with osteoporosis and poor liver function.
基金supported by the National Natural Science Foundation of China(32088101)National key Research and Development Program of China(2017YFC1700105,2021YFA1301603).
文摘Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.
基金This study was supported by the National Key Research and Development Program of the Ministry of Science and Technology of the People's Republic of China(2018YFC1704304).
文摘Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.
文摘using a WZD—1 microcirculation microscope,we observed the tongue tipand nail-bed microcirculation of uremic patients with deficiency of kidney-yangbefore and after blood dialysis.The results showed that the pathological basis ofuremia with deficiency of kidney-yang may be microcirculation disturbance,in-crease of metabolites and water retention.The effusion from capillary loops intongue tip may be one of the pathogenetic factors of a swollen and jaggedtongue.The flow rate of blood in capillary loops in the nail-bed was apparentlyabnormal and markedly improved after blood dialysis.The weighted integral ofnail-bed microcirculation decreased from moderately abnormal (4.99±1.52) toapproximately normal (1.98±0.97) (P【0.01).Microcirculation seems to be a sensi-tive criterion for reflecting the pathologic changes of uremia with deficiency ofkidney-yang.
基金Supported by the National Natural Science Foundation of China:Study on the Mechanism of Suspension Moxibustion with Moxa Stick in Treating Hydrocortisone Rats with Kidney-Yang Deficiency based on Hippocampus(amygdala)-HPA Axis(No.81660817)。
文摘OBJECTIVE:To investigated the effects of suspended moxibustion stimulating Shenshu(BL23)and Guanyuan(CV4)acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney-Yang deficiency symptom pattern(KYDS).METHODS:Sixty male Sprague Dawley rats were randomly divided into a control group(n=12)and an experimental group(n=48).Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model.The 48 rats successfully modeled were then randomly divided into a model group(model,n=12),a carbenoxolone intraperitoneal injection group(CBX,n=12),a moxibustion group(moxi,n=12),and a moxi+CBX group(n=12).In the moxi,the Shenshu(BL23)and Guanyuan(CV 4)acupoints were treated with moxibustion for 14 d.After treatment,measures were taken of serum levels of corticosterone(CORT),adrenocorticotropic hormone(ACTH),and corticotropinreleasing hormone(CRH).The expression of mineralocorticoid receptors(MRs),glucocorticoid receptors(GRs),11beta-hydroxysteroid dehydrogenase type 1(11β-HSD1),CRH,and ACTH in the rats’amygdala,hypothalamus,or pituitary(as appropriate)was detected.Data were analyzed using one-way analysis of variance.RESULTS:Compared with those of the control group,the serum levels of CRH,ACTH,and CORT;the mRNA and protein expressions of MR,GR,and 11β-HSD1 in the amygdala;the mRNA and protein expressions of 11β-HSD1 in the hypothalamus;the CRH mRNA expression in the amygdala and hypothalamus;and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased(P<0.05 or 0.01).After treatment with moxibustion,all the aforementioned observation indices except for 11β-HSD1 m RNA expression were ameliorated compared with those in the model group(P<0.05 or 0.01).CONCLUSIONS:Suspended moxibustion can effectively improve the serum levels of ACTH,CRH,and CORT and can up-regulate the mRNA and protein expressions of MR,GR,11β-HSD1,CRH,and ACTH in the amygdala and hypothalamus of KYDS rats.This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.
