贝那普利灌胃对糖尿病肾病大鼠肾组织连接蛋白表达的影响  

Effect of intragastric administration of benazepril on expression of connectin in diabetic nephropathy rats

作　　者：史伟佳 任琳琳 曹延萍[1] SHI Weijia;REN Linlin;CAO Yanping(Department of Nephrology,The First Hospital of Handan,Handan 056000,China;不详)

机构地区：[1]邯郸市第一医院肾内科,河北邯郸056000 [2]柘城县中医院医务科

出　　处：《山东医药》2024年第22期51-55,共5页Shandong Medical Journal

基　　金：河北省卫生健康委员会医学科学研究课题计划项目(20220503);邯郸市科学技术研究与发展计划项目(21422083054)。

摘　　要：目的探讨贝那普利对于糖尿病肾病大鼠肾脏连接蛋白(Cxs)表达的影响。方法将SD雄性大鼠分为对照组、糖尿病组、干预组,糖尿病组及干预组予以STZ 65 mg/kg一次性左下腹注射建立Ⅰ型糖尿病模型,对照组予以相同剂量的枸橼酸盐缓冲液腹腔注射。造模成功后第2天开始,干预组予贝那普利10 mg/(kg·d)每日定时灌胃,对照组和糖尿病组给予等量0.9%氯化钠溶液灌胃,治疗8周,测量各组体质量,采用酶电解层析法检测空腹血糖,采用双抗体夹心法检测尿微量白蛋白;分别应用肌氨酸氧化酶法、酶偶联速率法检测血肌酐、血尿素。8周后处死大鼠,应用SABC法观察连接蛋白Cx37、Cx40、Cx43在肾脏病理组织的分布,免疫组化法检测连接蛋白Cx37、Cx40、Cx43表达,RT-qRCR法检测Cx37、Cx40、Cx43 mRNA表达。结果与对照组相比,糖尿病组及干预组大鼠体质量较前明显下降,血糖较前明显升高(P均<0.05);干预组血尿素、血肌酐、尿微量白蛋白较糖尿病组均明显下降(P均<0.05)。糖尿病组Cx37、Cx43在出入球小动脉、近端肾小管分布明显减弱,干预组Cx37、Cx43在近端肾小管表达明显升高,糖尿病组可见Cx40在多处入球小动脉、致密斑分布明显减弱,干预组Cx40在致密斑分布增强。与糖尿病组比较,干预组Cx37、Cx40表达升高,差异有统计学意义(P均<0.05);干预组Cx43表达高于糖尿病组,差异无统计学意义(P>0.05)。Cx37 C_(T)值在糖尿病组明显升高,且对照组Cx37 C_(T)值高于干预组(P均<0.05)。三组Cx40 C_(T)值差异无统计学意义,干预组Cx40 C_(T)值较糖尿病组明显减小(P<0.05)。与对照组比较,糖尿病组Cx43 C_(T)值明显下降,干预组Cx43 C_(T)值明显上升,三组Cx43 C_(T)值差异均有统计学意义(P均<0.05)。结论贝那普利可上调糖尿病肾病大鼠肾脏连接蛋白表达,改善糖尿病肾病大鼠肾脏病理损伤,保护肾脏,延缓疾病进展。Objective To investigate the effect of benazepril on the expression of connexins(Cxs)in the renal tis⁃sues of diabetic nephropathy rats and its possible mechanism.Methods The SD male rats were divided into the control group,diabetes group,and intervention group.Rats in the diabetes group and intervention group were injected with STZ 65 mg/kg into the left lower abdomen once to establish the I-type diabetes models.Rats in the control group were injected with the same dose of citric acid buffer intraperitoneally.After the models were successfully established on the second day,rats in the intervention group were given benazepril 10 mg/(kg·d)by gavage daily at a fixed time,while rats in the control group and diabetes group were given the same volume of 0.9%sodium chloride solution.The treatment lasted for 8 weeks,during which,the body weight of each group was measured,fasting blood glucose was detected by enzymatic electrolytic chromatography,urinary microalbumin was detected by double-antibody sandwich method,and serum creatinine and urea were detected by sarcosine oxidase method and enzyme-coupled rate method,respectively.After 8 weeks,the rats were eu⁃thanized,and the distribution of connexin Cx37,Cx40,and Cx43 in the renal pathological tissues was observed by SABC method.The expression of connexin Cx37,Cx40,and Cx43 was detected by immunohistochemistry,and the expression of connexin Cx37,Cx40,and Cx43 mRNA was detected by RT-qRCR.Results Compared with the control group,the body weight of the diabetes group and the intervention group decreased significantly(P<0.05),and the blood glucose lev⁃el increased significantly(P<0.05);the blood urea nitrogen,blood creatinine,and urinary microalbuminuria of the inter⁃vention group were significantly lower than those of the diabetes group(all P<0.05).In the diabetes group,the distribu⁃tion of Cx37 and Cx43 in the efferent arterioles,afferent arterioles and proximal renal tubules was significantly weakened.In the intervention group,the expression of Cx37 and Cx43 in

关 键 词：糖尿病肾病 连接蛋白 贝那普利 大鼠 

分 类 号：R692.6[医药卫生—泌尿科学]