摘要
目的:探讨糖肾平胶囊对链脲佐菌素(STZ)诱导糖尿病肾病大鼠肾脏保护作用及其TGF-β1/p38MAPK信号通路影响。方法:雄性Wistar大鼠74只,随机分为正常组10只,模型组64只。模型组大鼠腹腔注射链脲佐菌素(STZ)(45mg/kg),模型成功的大鼠按体质量随机分为模型组、厄贝沙坦组、糖肾平胶囊低、高剂量组。每周称体质量,隔周分笼收集24h尿液检测24h尿蛋白定量。第14周,处死大鼠取血检测血尿素氮(BUN)、血清肌酐(Scr)、甘油三酯(TG)、丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)含量;肾组织行HE、Mallory、六胺银染色,观察肾组织的病理形态;肾组织原位杂交、RT-PCR、免疫组化观察转化生长因子β1(TGF-β1)、p38MAPK、Caspase-3 mRNA及蛋白表达。结果:模型组大鼠尿蛋白及血清BUN、Scr、TG、MDA含量显著增高(P<0.01),NO、SOD含量显著降低(P<0.01),肾固有细胞胞浆有大量TGF-β1、p38MAPK、Caspase-3 mRNA及蛋白表达;与模型组比较,各治疗组肾脏病理损害明显减轻,尿蛋白及血清BUN、Scr、TG、MDA含量显著降低(P<0.01),NO、SOD含量明显增高(P<0.01),肾固有细胞胞浆内TGF-β1、p38MAPK、Caspase-3 mRNA及蛋白表达明显减少(P<0.01),糖肾平治疗组呈剂量依赖关系。结论:糖肾平胶囊可能通过调控糖尿病肾病肾组织TGF-β1/p38MAPK信号表达,减轻足细胞在内的肾固有细胞凋亡,进而降低24h尿蛋白定量、改善肾功能、降低TG和MDA含量;升高NO、SOD含量;减轻肾脏病理损害,起到明显的糖尿病肾病肾脏保护及延缓病程进展的作用。
Objective： To explore the protectory effects of Tang Shen Ping Capsule on kidneys as well as its effects on TGF-β1/p38MAPK signal pathway in STZ-induced diabetic nephropathy rats.Methods： Seventy-four male Wistar rats were randomly divided into the normal group（n=10） and the model group（n=64）.The rats in the model group received Streptozotozin injection（45mg/kg）.Seventy two hours later,the model was considered successful if the blood glucose was ≥16.7mmol/L and urine glucose was ≥4＋.Then we randomly divided the successful model rats into four groups,namely,the model group,the irbesartan group,the low dose Tang Shen Ping Capsule group and the high dose Tang Shen Ping Capsule group.All the rats were weighed every week.We collected the 24 hour urine of all the rats in the first,second,fourth,eighth,twelfth and fourteenth week respectively and 24 hour urine protein quantitation was performed.After 14 weeks＇ treatment,all the rats were sacrificed and the biochemical indicators such as BUN,Scr,TG,MDA,NO and SOD were measured.All the nephridial tissues underwent HE,Mallory and hexamethylene tetramine sliver staining to observe pathological morphology of nephridial tissues.Immunohistochemistry,In situ hybridization and RT-PCR were performed to detect the expressions of TGF-β1,p38MAPK,Caspase-3 protein and mRNA.Results： Compared with the normal group,the BUN,Scr,TG and MDA levels were significantly higher（P0.01） while NO and SOD were significantly lower in the model group（P0.01）.Urine protein,BUN,Scr,TG and MDA were significantly lower and NO,SOD were significantly higher in all the treatment groups than in the model group（P0.01）.Immunohistochemistry,In situ hybridization and RT-PCR showed low expression of TGF-β1,p38MAPK,Caspase-3 protein and mRNA in normal renal roles of resident cells,and high expression in the model group.Compared with the model group,the expressions of TGF-β1,p38MAPK,Caspase-3 protein and mRNA were significantly lower in the treatment groups（P0.01）.A dose-dependent relationship was observed in Tang Shen Ping Capsule groups,and high dose Tang Shen Ping Capsule group was better than irbesartan group.Conclusion： Tang Shen Ping Capsule,which alleviates nephridial pathological lesions,has marked protectory effects on kidneys in diabetic nephropathy and delays the progress of disease course,possibly through down-regulated expressions of TGF-β1 and p38MAPK and decreased cell apoptosis of glomerular podocytes,which thus lowers 24 hour urine protein,blood fat and MDA and through increased NO,and SOD.This research provides experimental evidence for kideny wei in diabetic nephropathy.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2012年第4期1092-1097,I0004,I0005,共8页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然基金项目(No.30973831)
北京市中医管理局"51510"资助项目(No.JJ2007-006)~~
