论文部分内容阅读
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 microinflammation and renal oxidative stress in spontaneously hypertensive rats (SHR) and to investigate the effect of valsartan on the microinflammatory state and renal oxidative stress in SHR in vivo. Methods Fourteen male SHRs at 12 weeks of age were randomly divided into 2 groups (7 in each group): hypertension group (SHR group) and valsartan group (Val group, valsartan 50 mg / (kg · d) ). Seven male Wistar-Kyoto rats (WKY group), 12 weeks old, served as the control group for 8 weeks. Serum soluble klotho (s-kl) and interleukin-6 (IL-6) were detected by ELISA. Serum hs-CRP was detected by automatic biochemical analyzer. Proteins (FIB), ELC2010 instrument and supporting reagents for detection of ferritin (Fe). Thiobarbituric acid (TBA) method was used to detect intrarenal malondialdehyde (MDA), hydroxylamine method to measure total superoxide dismutase (T-SOD) activity, T-AOC Spectrophotometric determination of reduced glutathione (GSH). Results 1) The concentration of s-kl, the concentration of hs-CRP, FIB, Fe and IL-6 in SHR group were significantly increased (all P <0.05) And IL-6 levels were significantly down-regulated (all P <0.05). 2) The contents of MDA and GSH in renal tissue of SHR group were increased, while the contents of T-SOD and T-AOC were decreased (all P <0.05). The content of MDA and GSH decreased (P <0.05), the content of T-SOD and T-AOC increased (P <0.05), and the content of MDA, T-AOC and GSH remained different with the control group P <0.05). 3) Correlation analysis showed that there was a negative correlation between s-kl and hs-CRP, IL-6, MDA and GSH (all P <0.05) and positively correlated with T-AOC (all P <0.05). Conclusion The up-regulation of klotho levels in valsartan may be related to the reduction of micro-inflammation and oxidative damage, which may be one of the mechanisms of its delaying hypertensive renal impairment.