糖肾宝对糖尿病肾病大鼠肾脏保护作用的机制研究  

Protective mechanism of Tangshenbao on kidney of diabetic nephropathy rats

作　　者：钟文露 谢涛 胡维[2] 冉龙娇 甘慧芳 刘威利 韦海敏 向少伟[2] Zhong Wenlu;Xie Tao;Hu Wei;Ran Longjiao;Gan Huifang;Liu Weili;Wei Haimin;Xiang Shaowei(Graduate School of Guangxi University of Chinese Medicine,Nanning 530023,China;Department of Nephrology,Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Guangxi Clinical Medical Research Center of Integrative Medicine for Kidney Disease,Nanning 530023,China)

机构地区：[1]广西中医药大学研究生院,南宁530023 [2]广西中医药大学附属瑞康医院肾内科广西中西医结合肾脏疾病临床医学研究中心,南宁530023

出　　处：《国际中医中药杂志》2023年第2期174-180,共7页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81573906);广西自然科学基金项目(2020GXNSFAA297231、2021GXNSFAA220131)。

摘　　要：目的探讨糖肾宝对DN模型大鼠肾损伤的保护作用及其作用机制。方法将SPF级雄性SD大鼠36只按随机数字表法分为正常组6只、造模大鼠30只,采用单次大剂量腹腔注射链脲佐菌素(STZ)方法制备DN大鼠模型。将造模成功大鼠按随机数字表法分为模型组、厄贝沙坦组及糖肾宝低、中、高剂量组,每组6只。药物干预8周。记录各组大鼠一般情况及体重,检测大鼠血糖、肾脏指数、24 h尿蛋白定量(24 h UTP)、SCr、BUN水平,采用PAS染色、透射电镜观察肾组织病理形态;采用实时荧光定量PCR、Western blot检测肾组织E26转录因子-1(Ets-1)、TGF-β1、Smad2、Smad3 mRNA及蛋白表达。结果与模型组比较,糖肾宝低、中、高剂量组及厄贝沙坦组体重均升高(P<0.01),肾脏指数降低(P<0.05或P<0.01),24 hUTP、BUN、SCr均明显降低(P<0.05或P<0.01),肾小球体积明显缩小(P<0.05或P<0.01),肾组织Ets-1[(1.59±0.06)、(1.47±0.04)、(1.31±0.03)、(1.39±0.03)比(1.64±0.04)]、TGF-β1[(1.65±0.05)、(1.59±0.03)、(1.38±0.05)、(1.49±0.04)比(1.77±0.08)]、Smad2[(1.48±0.05)、(1.39±0.05)、(1.22±0.03)、(1.31±0.04)比(1.54±0.05)]、Smad3[(1.57±0.04)、(1.48±0.03)、(1.28±0.03)、(1.39±0.02)比(1.64±0.05)]mRNA水平降低(P<0.05或P<0.01),Ets-1[(1.33±0.32)、(1.16±0.38)、(0.77±0.06)、(0.84±0.06)比(1.97±0.43)]、TGF-β1[(1.35±0.14)、(1.24±0.22)、(0.94±0.13)、(1.07±0.06)比(1.63±0.20)]、Smad2[(1.24±0.26)、(1.14±0.31)、(0.77±0.28)、(0.85±0.19)比(1.72±0.34)]及Smad3[(1.29±0.14)、(1.19±0.21)、(0.85±0.39)、(0.90±0.37)比(1.76±0.21)]蛋白表达降低(P<0.05或P<0.01)。结论中药复方糖肾宝可改善DN大鼠肾损害,其机制可能与抑制Ets-1表达及TGF-β1/Smads信号通路传导有关。Objective To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy(DN)rats.Methods Totally 36 SPF male SD rats were randomly divided into normal group(n=6)and model group(n=30).The DN rat model was prepared by single high-dose intraperitoneal injection of STZ.According to the random number table method,the rats were divided into model group,irbesartan group and Tangshenbao low-,medium-and high-dosage groups,with 6 rats in each group.Drug intervention lasted for 8 weeks.The general condition and body weight of rats in each group were recorded.The blood glucose,kidney index,24 h urine protein(24 h UTP),SCr and BUN levels were detected.The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy.The mRNA and protein expressions of Ets-1,TGF-β1,Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot.Results Compared with model group,the body weight of Tangshenbao low,medium and high dose groups and irbesartan group significantly increased(P<0.01).The kidney index decreased(P<0.05 or P<0.01).The contents of 24 hUTP,BUN and SCr significantly decreased(P<0.05 or P<0.01).Glomerular volume was significantly reduced(P<0.05 or P<0.01),the mRNA expressions of Ets-1(1.59±0.06,1.47±0.04,1.31±0.03,1.39±0.03 vs.1.64±0.04),TGF-β1(1.65±0.05,1.59±0.03,1.38±0.05,1.49±0.04 vs.1.77±0.08),Smad2(1.48±0.05,1.39±0.05,1.22±0.03,1.31±0.04 vs.1.54±0.05),Smad3(1.57±0.04,1.48±0.03,1.28±0.03,1.39±0.02 vs.1.64±0.05)in renal tissue of rats significantly decreased(P<0.05 or P<0.01),the protein expressions of Ets-1(1.33±0.32,1.16±0.38,0.77±0.06,0.84±0.06 vs.1.97±0.43),TGF-β1(1.35±0.14,1.24±0.22,0.94±0.13,1.07±0.06 vs.1.63±0.20),Smad2(1.24±0.26,1.14±0.31,0.77±0.28,0.85±0.19 vs.1.72±0.34)and Smad3(1.29±0.14,1.19±0.21,0.85±0.39,0.90±0.37 vs.1.76±0.21)decreased(P<0.05 or P<0.01).Conclusion Tangshenbao can improve renal damage in DN rats,and its mechanism m

关 键 词：糖尿病肾病 糖肾宝 E26转录因子-1 转化生长因子Β1 SMAD蛋白 大鼠 

分 类 号：R285.5[医药卫生—中药学]