苯那普利对单侧输尿管梗阻大鼠肾组织TGF-β_1、α-SMA、NOX4表达的影响  

Effect of Benazepril on expression of TGF-β1, α-SMA and NOX4 in renal tissues of rats with unilateral ureteral obstruction

作　　者：赵燕云 项协隆 简怡娟 董飞侠 ZHAO Yanyun;XIANG Xielong;JIAN Yijuan;DONG Feixia(Department of Pharmacology, Wenzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medicine University Wenzhou, 325000;Department of Nephrology, Wenzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medicine University, Wenzhou, 325000;Department of Nephrology, Wenzhou Geriatric Hospital, Wenzhou, 325000)

机构地区：[1]浙江中医药大学附属温州中医院药剂科,浙江温州325000 [2]浙江中医药大学附属温州中医院肾内科,浙江温州325000 [3]温州老年病医院肾内科,浙江温州325000

出　　处：《温州医科大学学报》2017年第9期648-653,共6页Journal of Wenzhou Medical University

基　　金：浙江省自然科学基金资助项目(LY14H270001);浙江省中医药管理局课题(2013ZB121);温州市科技计划项目(Y20170692)

摘　　要：目的:观察苯那普利对单侧输尿管梗阻大鼠TGF-β_1、α-SMA、NOX4表达的影响,探讨苯那普利对肾间质纤维化的作用机制。方法:将54只SPF级SD大鼠随机分为假手术组、模型组、苯那普利组,每组18只。苯那普利组予1.6mg/kg苯那普利灌胃给药,每天1次,模型组、假手术组予10mL/kg0.9%氯化钠溶液灌胃,每天1次。模型组和苯那普利组大鼠均结扎左侧输尿管制备单侧输尿管梗阻肾纤维化模型。各组分别于造模第7、第14、第21天随机处死6只大鼠,取左侧肾脏组织做病理检测,Masson法观察肾纤维化程度,免疫组织化学染色检测肾组织TGF-β_1、α-SMA、NOX4的表达,PCR检测NOX4的表达情况。结果:与假手术组比,模型组大鼠肾间质纤维化程度加重,且随着输尿管梗阻时间延长而加重(P<0.05);与模型组比较,苯那普利组大鼠肾间质纤维化程度减轻(P<0.05)。免疫组织化学染色与PCR结果显示:与假手术组比,模型组肾组织TGF-β_1、α-SMA、NOX4表达明显增多(P<0.05);与模型组比,苯那普利组大鼠TGF-β_1、α-SMA、NOX4表达降低(P<0.05)。结论:苯那普利能下调单侧输尿管梗阻大鼠肾小管TGF-β_1、α-SMA、NOX4的表达,可能是其抗肾纤维化作用的机制之一。Objective:To observe the effects of Benazepril on expression of TGF-β1,α-SMA,NOX4inrenal tissues of rats with unilateral ureteral obstruction(UUO)and investigate the mechanism of it in renal interstitialfibrosis.Methods:The male Sprague-Dawley(SD)rats(54cases)were randomly divided into Sham-operatedgroup,model group and Benazepril treated group,18rats in each group.The benazepril group was given1.6mg/kg intragastric administration1times a day,and the model group and the sham operation group weregiven10mL/kg0.9%sodium chloride solution gavage1times a day,model group and the benazepril group wereligated left ureter to establish UUO models.At days7,14and21,six rats in each group were sacrificed.Theirleft surgery renal tissues were collected for pathological examination.The pathological changes of the obstructionrenal tissue were examined by Masson staining.The protein and gene expression of TGF-β1,α-SMA,NOX4was detected by immunohistochemical staining respectively and NOX4was detected by RT-PCR.Results:Comparedwith the Sham-operation group,the renal interstitial fibrosis degree of rats in other groups was increased(P<0.05),and aggratated as the ureteral obstruction time prolonged.Compared with the model group,after thetreatment,the renal interstitial fibrosis degree decreased significantly(P<0.05).Compared with the Sham-operationgroup,the protein expression of TGF-β1,α-SMA,NOX4in other group increased(P<0.05).Compared withthe model group,after the treatment by Benazepril,the protein expression TGF-β1,α-SMA,NOX4was downregulated in the renal tissue(P<0.05).Conclusion:Benazepril may effectively retard kidney interstitial fibrosisby reducing the expression of TGF-β1,α-SMA,NOX4to inhibit inflammatory of kidney.

关 键 词：单侧输尿管结扎 转化生长因子-β1 Α平滑肌肌动蛋白 NADPH氧化酶 肾纤维化 苯那普利 

分 类 号：R966[医药卫生—药理学]