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

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10 mg/(kg·d)],氯沙坦组50 mg/(kg·...

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

ObjectiveTo 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. MethodsFifteen 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.ResultsThe 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 (P<0.05 or P<0.01) in the fosinopril or losartan group. There was no significant difference in renal Mn SOD level among  the 4 groups (P>0.05). ConclusionFosinopril and losartan can exert protection against hypertensive renal damage through upregulating  Klotho expression as well as reducing  oxidative stress.