基于芳香烃受体干预MLCK/pMLC信号通路探讨肾衰宁颗粒对尿毒症腹膜透析大鼠肠屏障的保护作用  

Exploring the Protective Effect of Shenshuaining Granules on Intestinal Barrier in Uremic Peritoneal Dialysis Rats Based on Aryl hydrocarbon Receptor

作　　者：卫雅妮 兰欣蓉 范国荣 魏丽娟 邹文娟 杨洪涛[1] WEI Yani;LAN Xinrong;FAN Guorong(The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin,300382)

机构地区：[1]天津中医药大学第一附属医院,天津300382 [2]国家中医针灸临床医学中心,天津300382 [3]江西省进贤县人民医院,江西331700

出　　处：《中国中西医结合肾病杂志》2023年第10期858-861,I0001,共5页Chinese Journal of Integrated Traditional and Western Nephrology

摘　　要：目的:探讨肾衰宁颗粒对尿毒症(Uremia)腹膜透析(peritoneal dialysis,PD)大鼠肠屏障的保护机制。方法:40只大鼠随机分为假手术组、模型组及肾衰宁颗粒低、中、高剂量组,进行造模、给药等处理,给药结束后腹主动脉取血检测各组大鼠血清尿素氮(BUN)、血肌酐(Scr)、白蛋白(Alb)、谷丙转氨酶(ALT)、谷草转氨酶(AST)含量,HE及AB-PAS染色观察肠道组织病理形态变化;酶联免疫吸附法(ELISA)测定血清二胺氧化酶(DAO)、D-乳酸(D-LA)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)、脂多糖(LPS)水平,蛋白免疫印迹法(Western blot)观测大鼠结肠标本AhR、MLCK、pMLC蛋白表达情况。结果:与假手术组相比,模型组大鼠结肠组织损害明显,BUN、Scr、DAO、D-LA、TNF-α、hs-CRP、LPS水平明显上升(P<0.05),肾衰宁颗粒大鼠结肠组织病理损伤较模型组减轻,上述指标均明显降低,Alb水平明显升高(P<0.05)。与假手术组比较,模型组大鼠结肠组织AhR蛋白表达量降低、MLCK、pMLC蛋白表达量升高(P<0.05)。肾衰宁颗粒的干预有效逆转了模型组AhR、MLCK及pMLC蛋白表达量的改变。结论:肾衰宁颗粒可能通过调控AhR干预MLCK/pMLC通路,改善PD大鼠肠屏障功能障碍。Objective:To investigate the effect of Shenshuaining granules on the intestinal barrier of uremic peritoneal dialysis rats and its mechanism.Methods:A total of 40 rats were randomly divided into sham operation group,model group and low,medium and high dose groups of Shenshuaining granules.Those rats were treated with surgery and drug administration respectively.The abdominal aorta blood was collected to measure the serum urea nitrogen(BUN),blood creatinine(Scr),albumin(Alb),alanine aminotransferase(ALT)and glutathione aminotransferase(AST)at the end of drug administration.The pathological changes of intestinal histopathology were observed by hematoxylin eosin(HE)and AB-PAS.The serum diamine oxidase(DAO),D-Lactate(D-LA),tumor necrosis factor-α(TNF-α),hypersensitive C-reactive protein(hs-CRP),lipopolysaccharide(LPS)levels measured by enzyme-linked immunosorbent assay(ELISA).The protein expression of AhR,MLCK and pMLC in rat colon samples were observed by Western blot.Results:Compared with the sham-operated group,the colon tissue damage in the model group was obvious,and the levels of BUN,Scr,DAO,D-LA,TNF-α,hs-CRP and LPS were significantly increased(P<0.05).Compared with the model group,the pathological damage in the rats with Shenshuaining granules was reduced,and the above indicators were significantly reduced,while the level of Alb was significantly increased(P<0.05).Compared with the sham-operated group,AhR protein expression was significantly decreased,while the expressions of MLCK and pMLC protein were significantly increased in the model group(P<0.05).The intervention of Shenshuaining granules effectively reversed the alteration of AhR,MLCK and pMLC protein in the model group.Conclusion:Shenshuaining granules granules may interfere with the MLCK/pMLC pathway through modulation of AhR,improving intestinal barrier dysfunction in PD rats.

关 键 词：肾衰宁颗粒 尿毒症 腹膜透析 肠道 芳香烃受体 

分 类 号：R285.5[医药卫生—中药学]