卡格列净对糖尿病肾病的保护作用及对TGF-β1和CTGF表达的影响  

Protective mechanism of canagliflozin on diabetic nephropathy and its effect on the expressions of transforming growth factoRbeta1 and its downstream factoRconnective tissue growth factor

作　　者：曹冰[1] 张静[2] 陆晨 CAO Bing;ZHANG Jing;LU Chen(Department of Nephrology,the First Affiliated Hospital of Xinjiang Medical University,Xinjiang,Urumqi 830000,China;不详)

机构地区：[1]新疆医科大学第一附属医院肾内科,乌鲁木齐市830000 [2]新疆医科大学第五附属医院肾内科

出　　处：《河北医药》2023年第15期2286-2289,共4页Hebei Medical Journal

基　　金：新疆维吾尔自治区自然科学基金项目(编号:2020D01C219)。

摘　　要：目的探讨卡格列净对糖尿病肾病的保护作用机制及对转化生长因子(TGF-β1)和结缔组织生长因子(CTGF)表达的影响。方法建立对照组、糖尿病肾病组、卡格列净干预组3种大鼠模型,前2组给予蒸馏水灌胃,卡格列净干预组给予卡格列净灌胃,观察大鼠血糖及尿蛋白变化情况,持续灌胃37 d后处死大鼠;采用qRT-PCR方法检测肾脏组织中TGF-β1、CTGF基因表达水平,采用Westerm blot方法检测肾脏组织中TGF-β1、CTGF蛋白表达水平,观察3组间基因及蛋白的表达水平。结果卡格列净干预组在给药第18天后血糖水平明显低于糖尿病肾病组(P<0.05);卡格列净干预组处死前的尿蛋白定量水平明显低于糖尿病肾病组(P<0.05);糖尿病肾病组、卡格列净干预组的TGF-β1及CTGF的基因表达水平、大鼠肾脏组织中的TGF-β1及CTGF蛋白表达水平均明显高于对照组(P<0.05),卡格列净干预组的TGF-β1及CTGF的基因表达水平、大鼠肾脏组织中的TGF-β1及CTGF蛋白表达水平明显低于糖尿病肾病组(P<0.05)。结论卡格列净通过降低TGF-β1及其下游因子CTGF的表达水平,发挥糖尿病肾病保护作用。Objective To investigate the protective mechanism of canagliflozin inhibitoRon diabetic nephropathy and its effect on the expressions of transforming growth factoRbeta1(TGF-β1)and its downstream factoRconnective tissue growth factoR(CTGF).Methods Rats were randomly divided into control group,diabetic nephropathy group and canagliflozin group,and those in the latteRtwo groups were subjected to the modeling of diabetic nephropathy.Rats in the control group and diabetic nephropathy group were intervened by gavage of distilled water,and those in the latteRgroup were intervend by gavage of canagliflozin.Changes of blood glucose and urine protein were observed.Rats were sacrificed afteRa continuous gavage foR37 days.The mRNA and protein expressions of TGF-β1 and CTGF in kidney tissues were detected by quantitative real-time PCR(qRT-PCR)and Western blot(WB).The expression levels of genes and proteins between groups were observed.Results The blood glucose in the canagliflozin group was significantly loweRthan that in the diabetic nephropathy group on the 18th day of administration(P<0.05).Urine protein level in the canagliflozin group before sacrifice was significantly loweRthan that in the diabetic nephropathy group(P<0.05).The mRNA and protein expressions of TGF-β1 and CTGF in the diabetic nephropathy group and the canagliflozin group were significantly higheRthan those in the control group(P<0.05),which,in canagliflozin group were significantly loweRthan those of diabetic nephropathy group(P<0.05).Conclusion canagliflozin can protect diabetic nephropathy by downregulating TGF-β1 and its downstream factoRCTGF.

关 键 词：卡格列净 糖尿病肾病 转化生长因子Β1 结缔组织生长因子 

分 类 号：R587.24[医药卫生—内分泌]