丹酚酸B对糖尿病大鼠肾纤维化的改善作用及其机制  

Ameliorative effect of salvianolic acid B on renal fibrosis in diabetic rats and potential mechanisms implicated

作　　者：张旭[1] 朱元美[1] 唐保露 任尤楠 陶善珺 杨解人[1] 郑书国[1,3,4] ZHANG Xu;ZHU Yuan-mei;TANG Bao-lu;REN You-nan;TAO Shan-jun;YANG Jie-ren;ZHENG Shu-guo(Dept of Pharmacology, Wannan Medical College, Wuhu Anhui 241002, China;Dept of Anatomy, Wannan Medical College, Wuhu Anhui 241002, China;Institute of Quantitative Pharmacology, Wannan Medical College, Wuhu Anhui 241002, China;Drug Research and Development Center, Wannan Medical College, Wuhu Anhui 241002, China)

机构地区：[1]皖南医学院药理学教研室,安徽芜湖241002 [2]皖南医学院解剖学教研室,安徽芜湖241002 [3]皖南医学院定量药理研究所,安徽芜湖241002 [4]皖南医学院药物研发中心,安徽芜湖241002

出　　处：《中国药理学通报》2019年第1期51-55,共5页Chinese Pharmacological Bulletin

基　　金：安徽高校省级自然科学研究重点项目(No KJ2015A192);中国医药教育协会孙思邈中医药科研专项课题(No 164-33);皖南医学院科研项目培育基金重点项目(No WK2017Z09)

摘　　要：目的观察丹酚酸B对糖尿病大鼠肾纤维化的影响,并探讨其可能机制。方法采用高糖高脂饮食,合并腹腔注射链脲佐菌素(STZ)的方法建立糖尿病大鼠模型。将糖尿病大鼠随机分为模型组、丹酚酸B低、高剂量组(80、160 mg·kg^(-1))。丹酚酸B各组每天灌胃给予相应剂量药物,正常对照组和模型组灌胃相应容量生理盐水,连续6周。实验结束时检测大鼠空腹血糖(FBG)、血清肌酐(SCr)、尿素氮(BUN)、尿微量白蛋白(UAlb),以及血清丙二醛(MDA)、总抗氧化能力(TAC)和超氧化物歧化酶(SOD)水平;Masson染色法观察肾组织胶原纤维水平;ELISA法检测肾组织Ⅰ型和Ⅲ型胶原含量;Western blot法检测肾组织转化生长因子β1(TGF-β1)、p-Smad2和Smad7蛋白水平。结果丹酚酸B可明显减少糖尿病大鼠肾组织胶原沉积,降低FBG、BUN、UAlb、SCr、MDA及TGF-β1、p-Smad2蛋白水平,使血清TAC、SOD活性和肾组织Smad7蛋白水平明显升高(P<0.01或P<0. 05)。结论丹酚酸B可明显减轻糖尿病大鼠肾纤维化,改善肾功能,其机制与改善氧化应激状态、调控TGF-β1/Smad信号通路有关。Aim To investigate the ameliorative effect of salvianolic acid B(Sal B)on renal fibrosis in diabetic rats and the possible mechanisms implicated.Methods Diabetes in SD rats was induced by high sugar high fat diet combined with intraperitoneal injection of streptozotocin(STZ,40mg·kg^-1).Diabetic rats were allocated randomly to model group,high dose of Sal B group(160mg·kg^-1)and low dose of Sal B group(80mg·kg^-1).Rats in Sal B groups were administered intragastrically with corresponding dose of Sal B for six weeks,while those in the control and model group were given distilled water of the same volume.At the end of experiment,the levels of fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),urine microalbumin(UAlb),serum malondialdehyde(MDA),total antioxidant capacity(TAC)and superoxide dismutase(SOD)were determined with commercially available kits.Renal fibrosis was evaluated by Masson staining and renal contents of typeⅠand typeⅢcollagen determined by ELISA.The protein levels of TGF-β1,p-Smad2and Smad7were evaluated by Western blot analysis.Results In model group,the levels of FBG,SCr,BUN,UAlb and MDA significantly increased as compared with those in control group,while TAC and SOD activities decreased markedly(P<0.01).Rats in model group exhibited evident renal fibrosis,accompanied by significantly increased levels of TGF-β1and p-Smad2protein and decreased level of Smad7protein in renal tissues(P<0.01).Supplementation with Sal B significantly ameliorated renal fibrosis in diabetic rats,with TGF-β1and p-Smad2protein down-regulated and Smad7protein up-regulated evidently(P<0.05or P<0.01).The above mentioned changes in biochemical parameters were also reversed markedly in Sal B treated groups(P<0.05or P<0.01).Conclusions Sal B is capable of ameliorating renal fibrosis in diabetic rats,which might be related to its antioxidant property and regulation of TGF-β1/Smad signaling pathway.

关 键 词：糖尿病 肾纤维化 丹酚酸B TGF-Β1 氧化应激 糖尿病肾病 

分 类 号：R-332[医药卫生] R284.1