摘要
目的:黄连总生物碱对溃疡性结肠炎(UC)模型大鼠肠黏膜损伤的保护作用,并初步探究其可能的作用机制。方法:将60只大鼠随机分为6组:正常对照组、模型组、黄连总生物碱低(0.1 g·kg^-1)、中(0.2 g·kg^-1)、高(0.3 g·kg^-1)剂量组、阳性对照组(柳氮磺吡啶,0.6 g·kg^-1)组,每组10只。建立UC大鼠模型,造模4 d后各组灌胃给药,1次/d,给药容积为每只10ml,正常对照组和模型组给予等量生理盐水,连续给药2周。观察大鼠一般情况,评估大鼠结肠组织大体形态学损伤情况;HE染色观察结肠组织病理损伤情况;Elisa法检测结肠组织匀浆液中白介素-6(IL-6)、白介素^-10(IL^-10)、肿瘤坏死因子-α(TNF-α)水平;Western blot检测结肠组织中p38、过氧化物酶体增殖物激活受体γ(PPARγ)、核因子κB(NF-κB)蛋白表达;免疫组化法检测结肠组织中PPARγ、NF-κB蛋白阳性表达情况。结果:正常对照组大鼠无异常性改变;模型组大鼠毛发干枯、精神倦怠、肛周污秽、大便黏腻、体型明显消瘦,经黄连总生物碱干预后,大鼠体质量升高,精神状态好转,饮食增加,大便粘腻、出血情况得到有效改善。与正常对照组相比,模型组结肠组织大体形态损伤评分、肠黏膜损伤评分、IL-6和TNF-α水平、p-p38 MAPK和NF-κB蛋白表达水平、NF-κB蛋白表达阳性率显著升高,IL^-10水平、PPARγ蛋白表达水平和阳性率显著降低(P<0.05)。与模型组相比,黄连总生物碱各剂量组和阳性对照组结肠组织大体形态损伤评分、肠黏膜损伤评分、IL-6和TNF-α水平、p-p38MAPK和NF-κB蛋白表达水平、NF-κB蛋白表达阳性率显著降低,IL^-10水平、PPARγ蛋白表达水平和阳性率显著升高(P<0.05),黄连总生物碱组的作用呈剂量依赖性(P<0.05)。结论:黄连总生物碱能够缓解溃疡性结肠炎模型大鼠肠黏膜损伤,激活PPARγ,抑制p38/NF-κB通路,减轻结肠组织炎症反应。
Objective: To investigate the protective effect of the total alkaloids of Coptis chinensis on intestinal mucosal injury in rats with ulcerative colitis( UC),and explore its possible mechanism. Methods: Totally 60 rats were randomly divided into 6 groups:the normal control group,the model group,the total alkaloids of Coptis chinensis low( 0.1 g·kg^-1),medium( 0.2 g·kg^-1) and high( 0.3 g·kg^-1) dose groups and the positive control group( sulfasalazine,0.6 g·kg^-1) with 10 rats in each group. UC rat model was established. After 4 days,each group was given corresponding drug orally once a day with a volume of 10 ml for each rat. The normal control group and the model group were given the same amount of saline for 2 weeks. The general situation of rats was observed,the morphological damage of colon tissue in rats was evaluated,HE staining was used to observe the pathological damage of colon tissues,the levels of interleukin-6( IL-6),interleukin^-10( IL^-10) and tumor necrosis factor-α( TNF-α) in colon homogenate were measured by Elisa method,Western blot was used to detect the expressions of mitogen-activated protein kinase( p38),peroxisome proliferatoractivated receptorγ( PPARγ) and nuclear factor κB( NF-κB) in colon tissues,and immunohistochemical method was used to detect the positive expressions of PPARγ and NF-κB protein in colon tissue. Results: There were no abnormal changes in the normal control group,while the model group had dry hair,mental burnout,perianal contamination,greasy stool and marked emaciation. After the intervention with the total alkaloids of Coptis chinensis,the body weight of rats was increased,the mental state was improved,the diet was increased,and their stool stickiness and hemorrhage were effectively improved. Compared with those in the normal control group,the gross morphological injury score,intestinal mucosal injury score,IL-6 and TNF-α levels,protein expression levels of p-p38 MAPK and NF-κB,and the positive rate of NF-κB protein expression in the model group increased significantly,while the level of IL^-10,protein expression and positive rate of PPARγ decreased significantly( P<0.05). Compared with those in the model group,the gross morphological injury score,intestinal mucosal injury score,IL-6 and TNF-α levels,protein expression levels of p-p38 MAPK and NF-κB,and positive rate of NF-κB protein expression in the total alkaloids of Coptis chinensis groups and the positive control group decreased significantly,while the level of IL^-10,protein expression and positive rate of PPARγ increased significantly( P<0.05). The effect of the total alkaloids of Coptis chinensis was dose-dependent( P<0.05). Conclusion: The total alkaloids of Coptis chinensis can alleviate intestinal mucosal injury and inflammatory reaction in rats with ulcerative colitis,which may be achieved by activating PPARγ and inhibiting p38/NF-κB pathway.
作者
蒋晓梅
刘翀
朱延焱
Jiang Xiaomei;Liu Chong;Zhu Yanyan(Department of Pharmacy,Lishui Central Hospital,Zhejiang Lishui 323000,China)
出处
《中国药师》
CAS
2019年第12期2188-2193,共6页
China Pharmacist
关键词
黄连总生物碱
溃疡性结肠炎
肠黏膜损伤
过氧化物酶体增殖物激活受体
丝裂原活化蛋白激酶
核因子κB
Total alkaloids of Coptis chinensis
Ulcerative colitis
Intestinal mucosal injury
Peroxisome proliferator-activated receptor
Mitogen-activated protein kinase
Nuclear factor κB
