摘要
目的旨在探究大黄酸对糖尿病性肾病(DN)模型大鼠肾的防护效果,并研讨其潜在的作用机制。方法选用45只雄性SD大鼠采用随机数字表法分配至4个实验组,正常组10只、模型组15只、大黄酸组10只以二甲双胍组10只,正常组维持日常饲养,另外3组则建立DN的实验模型,并通过灌胃方式分别给予相应的治疗药物。在特定时间对大鼠的体重、禁食血糖(FBG)、血尿素氮(BUN)含量、血清肌酐(Scr)水平、24 h尿量以及尿蛋白含量进行测定,采用酶联免疫吸附测定(ELISA)法检测各组大鼠肾组织中MDA浓度以及SOD和GSH-Px活性,观察各组大鼠肾组织的病理变化,Western blot技术检测Sestrin、Nrf、TGF-β_(1)、Smad3等蛋白在肾组织中的表达水平。结果与正常组相比,模型组大鼠体重、SOD和GSH-Px活性、Sestrin2、Nrf2蛋白表达降低(P<0.05),FBG、BUN、Scr、肾组织MDA水平和TGF-β_(1)、Smad3蛋白表达升高(P<0.05),肾组织出现明显病理损伤;与模型组相比,经大黄酸与二甲双胍干预后的大鼠体重、SOD和GSH-Px活性、Sestrin2、Nrf2蛋白表达升高(P<0.05),FBG、BUN、Scr、肾组织MDA水平和TGF-β_(1)、Smad3蛋白表达降低(P<0.05),肾病理损伤得以缓解;与大黄酸组相比,二甲双胍组大鼠FBG降低(P<0.05),肾TGF-β_(1)蛋白表达升高(P<0.05)。结论大黄酸具备抵御糖尿病肾病影响的能力,其可能的机制包括促进肾功能的恢复、调节氧化应激反应、加强肾脏组织内Sestrin和Nrf蛋白表达,进而减少肾TGF-β_(1)和Smad3蛋白的表达。
Objective The study aimed to investigate the protective effect of rhein on the kidney of rats with diabetic nephropathy(DN)and explore its potential mechanism.Methods Forty-five male SD rats were randomly divided into four experimental groups:normal group(n=10),model group(n=15),rhein treatment group(n=10)and metformin treatment group(n=10).The rats in normal group were fed with normal diet,while in the other three groups the experimental models of DN were established and rats were treated with corresponding drugs by gavage.The body weight,fasting blood glucose(FBG),blood urea nitrogen(BUN),serum creatinine(Scr),24 h urine volume and urine protein content were measured at specific times.Enzyme-linked immunosorbent assay(ELISA)was used to detect the concentration of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the kidney tissues of rats in each group along with the pathological changes.Western blot was applied to detect the expression levels of Sestrin,Nrf,TGF-β_(1),Smad3 and other proteins in renal tissue.Results Compared with the normal group,the body weight,SOD and GSH-Px activities,Sestrin2 and Nrf2 protein expression in the model group were decreased(P<0.05),FBG,BUN,Scr,MDA level in renal tissue and TGF-β_(1),Smad3 protein expression were increased(P<0.05),and obvious pathological damage was observed in renal tissue.Compared with the model group,the body weight,SOD and GSH-Px activities,Sestrin2 and Nrf2 protein expression of the rats were increased(P<0.05)after the intervention of rhein and metformin,while FBG,BUN,Scr,MDA level in renal tissue and TGF-β_(1) and Smad3 protein expression were decreased(P<0.05),and renal pathological injury was alleviated.Compared with the rhein group,the metformin group had a significant reduction in FBG(P<0.05)and a significant increase in renal TGF-β_(1) protein expression(P<0.05).Conclusion Rhein can resist the influence of diabetic nephropathy,and its possible mechanisms include promoting the recovery of re-nal function,regulating oxidative stress,enhancing the expression of Sestrin and Nrf proteins in renal tissue,and thus reducing the ex-pression of TGF-β_(1) and Smad3 proteins in renal tissue.
作者
王莉
辛华
赵玉德
石国欣
胡宇
王李鸣
王瑞隆
郑小鹏
WANG Li;XIN Hua;ZHAO Yude;SHI Guoxin;HU Yu;WANG Liming;WANG Ruilong;ZHENG Xiaopeng(Department of Laboratory Medicine,the First Affiliated Hospital of Jiamusi University,Jiamusi 154003,Heilongjiang,China)
出处
《医学研究与战创伤救治》
北大核心
2025年第8期814-820,共7页
Journal of Medical Research & Combat Trauma Care
基金
黑龙江省高等学校基本科研业务费(2024-KYYWF-0575)
佳木斯大学创新人才培养计划项目(JMSUQP2023024)。
