隐丹参酮对STZ诱导的糖尿病肾病模型大鼠的肾脏保护作用及机制  

Protective effect and mechanism of cryptotanshinone on kidney of rats with STZ-induced diabetic nephropathy

作　　者：王卫娜[1] 马凤巧[1] 王运贤[1] 刘前[2] WANG Weina;MA Fengqiao;WANG Yunxian;LIU Qian(Department of basic medicine,Nanyang Medical College,Nanyang 473000,China;The First Affiliated Hospital of Nanyang Medical College,Nanyang 473000,China)

机构地区：[1]南阳医学高等专科学校基础医学部,河南南阳473000 [2]南阳医学高等专科学校第一附属医院,河南南阳473000

出　　处：《沈阳药科大学学报》2024年第10期1369-1374,1385,共7页Journal of Shenyang Pharmaceutical University

基　　金：河南省2018年科技发展计划项目(182102310691)。

摘　　要：目的探讨隐丹参酮对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病(diabetic nephropa-thy,DN)模型大鼠肾脏保护作用及可能作用机制.方法60只大鼠按随机数字表法分为对照组,DN模型组,隐丹参酮低、中、高剂量组(15、30、60 mg·kg^(-1)·d^(-1))和二甲双胍组(200 mg·kg^(-1)·d^(-1)),除对照组,其余均以STZ诱导制成DN大鼠模型.给药结束24 h后,检测大鼠的空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白中胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、24h尿蛋白定量、血尿素氮(BUN)、血清肌酐(Scr)、超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)指标;Western blot检测TGF-β1/Smad3信号通路相关蛋白表达水平.结果生化指标检测结果显示:经药物干预后,二甲双胍组和隐丹参酮中、高剂量组大鼠FPG、尿蛋白、BUN、Scr、MDA、ROS、TG、TC、LDL-C水平、全血高切黏度、全血中切黏度、全血低切黏度及血浆黏度水平均较DN模型组降低,而SOD、HDL-C水较DN模型组升高.Western blot结果显示:经药物干预后,二甲双胍组和隐丹参酮中、高剂量组大鼠TGF-β1蛋白表达水平、p-Smad3/Smad3比值较DN模型组降低,而p-Smad7/Smad7比值较DN模型组升高.结论隐丹参酮可改善STZ诱导的DN模型大鼠的糖脂代谢、氧化应激及血液流变学情况,提升大鼠的肾功能,其保护作用可能与激活TGF-β1/Smad3信号通路有关.Objective To explore the effects and possible action mechanisms of cryptotanshinone on kidney in rats with diabetic nephropathy(DN)induced by streptozotocin(STZ).Methods According to random number table method,60 rats were divided into control group,DN model group,low-dose,medium-dose and high-dose cryptotanshinone groups(15,30,60 mg·kg^(-1)·d^(-1)),and metformin group(200 mg·kg^(-1)·d^(-1)).Except for control group,rats in the other groups were induced by STZ to prepare DN rat models.At 24h after the end of administration,plasma glucose(FPG),triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),24h urine protein quantification,blood urea nitrogen(BUN),serum creatinine(Scr),superoxide dismutase(SOD),malondialdehyde(MDA)and reactive oxygen species(ROS)were detected.The expression levels of proteins related to TGF-β1/Smad3 signaling pathways were detected by Western blot.Results The detection results of biochemical indexes showed that after drug intervention,levels of FPG,urine protein,BUN,Scr,MDA,ROS,TG,TC,LDL-C,high-shear,mid-shear and low-shear viscosity,and plasma viscosity in metformin group,medium-dose and high-dose cryptotanshinone groups were lower than those in DN model group,while levels of SOD and HDL-C were higher than those in DN model group.The results of Western blot showed that after drug intervention,expression level of TGF-β1 protein and p-Smad3/Smad3 ratio in metformin group,medium-dose and high-dose cryptotanshinone groups were lower than those in DN model group,while p-Smad7/Smad7 ratio was higher than that in the DN model group.Conclusion Cryptotanshinone can improve glucose-lipid metabolism,oxidative stress and hemorheology in rats with STZ-induced DN,and enhance their renal function.The protective mechanisms may be related to activating TGF-β1/Smad3 signaling pathways.

关 键 词：糖尿病肾病 隐丹参酮 TGF-β1/Smad3信号通路 氧化应激 高脂血症 大鼠模型 

分 类 号：R96[医药卫生—药理学]