福辛普利、氯沙坦对自发性高血压大鼠Klotho表达及氧化应激的影响(英文)  

Effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats

作　　者：唐荣[1] 周巧玲[1] 刘志纯[1] 肖舟[1] Veeraragoo Pouranan 

机构地区：[1]中南大学湘雅医院肾内科,长沙410008

出　　处：《中南大学学报（医学版）》2011年第1期27-33,共7页Journal of Central South University ：Medical Science

基　　金：supported by the grant of Creative Study of Central South University(YA08064)

摘　　要：目的:观察福辛普利(fosinopril)和氯沙坦(losartan)对自发性高血压大鼠(SHR)肾脏Klotho表达及氧化应激的影响,探讨其对高血压肾损伤的保护作用机制。方法:15只22周龄雄性SHR,随机分为3组(5只/组);模型组(SHR组),福辛普利组[10mg/(kg.d)],氯沙坦组[50mg/(kg.d)];以22周龄雄性Wistar-Kyoto(WKY)大鼠5只为正常对照,共喂养8周。检测尾动脉收缩压、24h尿蛋白定量(Upro)、尿N-乙酰-8-D-氨基葡萄糖苷酶(NAG酶)等指标。HE染色观察大鼠肾脏病理改变,RT-PCR、免疫组织化学及Western印迹检测Klotho蛋白及mRNA表达;并检测肾脏总抗氧化能力(T-AOC)、丙二醛(MDA)、铜锌超氧化物歧化酶(Cu/Zn-SOD)、锰超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)水平。结果:模型组肾脏出现高血压肾损伤的病理特征。与模型组比较,福辛普利或氯沙坦组收缩压、Upro及尿NAG酶均明显降低,肾脏病理损伤减轻(P<0.05)。肾脏Klotho蛋白及mRNA表达均明显上调(P<0.05),同时肾脏MDA含量降低,T-AOC,Cu/Zn-SOD,CAT及GSH-Px活性均较模型组增加(P<0.05或P<0.01),Mn-SOD活性无明显改变(P>0.05)。结论:福辛普利、氯沙坦可通过上调抗衰老基因Klotho在肾脏中的表达,并抑制氧化应激,从而对高血压肾损伤起保护作用。Objective To explore effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats（SHR） and the mechanisms underlying the protection against renal damage.Methods Fifteen male SHRs（22 weeks old） were randomly divided into 3 groups（n=5 in each group）：a SHR group,a fosinopril group [10 mg/（kg·d）],and a losartan group [50 mg/（kg·d）].Age-matched Wistar-Kyoto（WKY） rats were chosen for a control group.Eight weeks later,tail arterial pressure,24 hours urinary protein（Upro）,urinary N-acetyl-β-D-glucosaminidase（NAGase） were measured.Renal pathological changes were examined under light microscopy by HE staining.The renal mRNA and protein expression of Klotho were determined by RT-PCR,immunohistochemical staining or Western blot.The levels of total antioxidant capacity（TAOC）,malondialdehyde（MDA）,Cu/Zn superoxide dismutase（Cu/Zn-SOD）,Mn superoxide dismutase（Mn-SOD）,catalase（CAT）,and glutathione peroxidase（GSH-Px） were determined.Results The typical pathological characteristics of hypertensive renal damage were observed in the kidney of the SHR group.Compared with the SHR group,the systolic pressure,Upro,and urinary NAGase,the content of MDA and renal pathological damage was reduced while the renal Klotho expression and activities of TAOC,Cu/Zn-SOD,CAT,and GSH-Px were increased（P0.05 or P0.01） in the fosinopril or losartan group.There was no significant difference in renal Mn-SOD level among the 4 groups（P0.05）.Conclusion Fosinopril and losartan can exert protection against hypertensive renal damage through upregulating Klotho expression as well as reducing oxidative stress.

关 键 词：福辛普利 氯沙坦 KLOTHO 氧化应激 高血压肾损伤 

分 类 号：R544.1[医药卫生—心血管疾病]