缬沙坦上调klotho蛋白表达对SHR微炎症及肾氧化应激的影响  

Effect of up-regulated klotho expression by valsartan on micro inflammatory state and renal oxidative stress in SHR

作　　者：林书典[1] 詹锋[1] 武伟[1] 潘楚瑛[1] 符克英[1] 张延[1] 陈道军[1] 杨舟[1] 黄艳艳[1] 刘颖[1] 黄玮[1] 

机构地区：[1]海南省人民医院肾病风湿科,海南海口570311

出　　处：《中国热带医学》2016年第2期97-100,共4页China Tropical Medicine

基　　金：国家自然科学基金(No.81360118);海南省自然科学基金(No.309087)

摘　　要：目的研究自发性高血压模型鼠(SHR)体内微炎症及肾脏氧化应激状态,探讨缬沙坦上调klotho蛋白表达对SHR体内微炎症状态和肾脏氧化应激的影响。方法 12周龄雄性SHR 14只,随机分为2组(每组7只):高血压组(SHR组)和缬沙坦组(Val组,缬沙坦50 mg/(kg·d)灌胃);12周龄雄性Wistar-Kyoto大鼠7只(WKY组),为对照组,共喂养8周。采用ELISA法检测血中可溶性klotho(s-kl)和白细胞介素-6(IL-6),全自动生化分析仪检测血超敏C反应蛋白(hs-CRP),全自动血凝仪检测纤维蛋白原(FIB),ELC2010仪及配套试剂检测铁蛋白(Fe)。硫代巴比妥酸(TBA)法检测肾内丙二醛(MDA),羟胺法检测总超氧化物歧化酶(T-SOD)活性,比色法检测总抗氧化力(T-AOC),分光光度法检测还原性谷胱甘肽(GSH)。结果 1)SHR组大鼠血中s-kl浓度降低,hs-CRP、FIB、Fe和IL-6浓度增高(P均<0.05),经缬沙坦干预后s-kl浓度上升,hs-CRP和IL-6浓度显著下调(P均<0.05)。2)SHR组大鼠肾组织MDA和GSH含量升高,T-SOD和T-AOC含量下降(P均<0.05)。经缬沙坦干预后MDA和GSH含量降低(P均<0.05),T-SOD和T-AOC含量上升(P均<0.05),且MDA、T-AOC和GSH含量与对照组仍有差异(P均<0.05)。3)相关分析提示:s-kl与hs-CRP、IL-6、MDA及GSH呈负相关关系(P均<0.05),与T-AOC呈正相关关系(P均<0.05)。结论缬沙坦上调klotho水平与减轻微炎症和氧化损伤有关,可能是其延缓高血压肾损害的机制之一。Objective To study the micro- inflammation and renal oxidative stress in spontaneously hypertensive rats（SHR）,and to illuminate the role of up-regulated klotho expression by valsartan on micro-inflammatory state and oxidative stress in SHR. Methods Fourteen 12 week-old male SHRs were randomly divided into 2 groups at seven for each group：hypertensive group（SHR）and valsartan group（Val group,treated with Valsartan for 50 mg/kg/d）; seven 12 week-old male Wistar- Kyoto rats（WKY）as the control. After 8 weeks,the serum soluble klotho（s- kl）and interleukin- 6（IL- 6）were measured by ELSIA,high- sensitivity C- reactive protein（hs- CRP）,fibrinogen（FIB）and ferritin（Fe）were measured by conventional methods. Malondialdehyde（MDA）was detected by thiobarbituric acid method（TBA）.Total antioxidant power（TAOC）was measured by colorimetry,and total superoxide dismutase（T- SOD）activity and reduced glutathione（GSH）were determined by hydroxylamine method and spectrophotometry,respectively. Results 1. The level of surum s-kl was decreased in SHR,but the hs-CRP,FIB,Fe and IL-6 concentrations were increased（P〈0.05）while the rats were treated with valsartan,the s-kl increased,and the hs-CRP and IL-6 concentrations were decreased obviously viewed in serum（P〈0.05）. 2. In renal tissue of SHR,the MDA and GSH were increased,and the T-SOD and T-AOC were decreased compared to WKY（P〈0.05）. A lower level of MDA and GSH,and a higher level of T-SOD and T-AOC in SHR treated with valsartan were observed. However,there was statistical difference in the MDA,T-AOC and GSH between Val group and WKY. 3 Correlation analysis indicated that s-kl was negatively correlated with hs-CRP,IL-6,MDA and GSH（P〈0.05）,positively correlated with T-AOC（P〈0.05）.Conclusion Up- regulated klotho by valsartan is closely related to the relieving micro- inflammation and renal oxidative injury,which may be one of the mechanisms of delaying the renal damage by hypertension.

关 键 词：KLOTHO蛋白 缬沙坦 微炎症 氧化应激 

分 类 号：R96[医药卫生—药理学]