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目的探讨贝特类药物对脑卒中易感型自发性高血压大鼠(SHRsp)肾脏氧化应激水平的影响及可能机制。方法将2月龄雄性SHRsp10只随机分为两组,自由摄食标准饲料组(SHRsp,n=5),摄食添加0.25%氯贝特标准饲料组(氯贝特,n=5);用免疫印迹法检测肾组织中羟甲基戊二酸单酰辅酶A合成酶(HMGCS2)表达差异以及细胞信号磷酸化水平;使用试剂盒测量肾组织中丙二醛含量及抗氧化物酶活性[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)]。结果与SHRsp组比较,氯贝特组丙二醛[(0.21±0.02)比(0.79±0.10)nmol/mgpro]、CAT[(38.46±1.02)比(46.65±3.52)U/mgpro]、SOD[(20.13±0.28)比(22.59±0.90)NU/mgpro]均降低(均P<0.05),而两组间GSH-Px活性比较,差异无统计学意义(P>0.05);SHRsp组HMGCS2表达量显著低于氯贝特组;氯贝特显著降低SHRsp肾组织蛋白激酶B的磷酸化水平。结论氯贝特类药物在不上调抗氧化物酶活性情况下,能降低自发性高血压大鼠肾脏氧化应激水平,其机制可能与HMGCS2蛋白高表达有关。
Objective To investigate the effects of fibrates on renal oxidative stress in stroke-prone spontaneously hypertensive rats (SHRsp) and its possible mechanism. Methods Two-month-old male SHRsp10 mice were randomly divided into two groups. The rats were randomly fed the standard diet (SHRsp, n = 5), fed with 0.25% Method to detect the expression of HMGCS2 and the level of phosphorylation of cell signal in renal tissue. The content of malondialdehyde and the activity of antioxidant enzymes in renal tissue were measured using a kit [superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GSH-Px)]. Results Compared with the SHRsp group, the MDA content in the clofibrate group was significantly higher than that in the control group (0.21 ± 0.02 vs 0.79 ± 0.10 nmol / mgpro, CAT [(38.46 ± 1.02) vs 46.65 ± 3.52 U / mgpro] (20.13 ± 0.28) vs (22.59 ± 0.90) NU / mgpro] (all P <0.05), while there was no significant difference in the activity of GSH-Px between the two groups (P> 0.05) Significantly lower than that of the fibrate group; and that of the fibrate group significantly decreased the phosphorylation of protein kinase B in the SHRsp kidney tissue. Conclusion Clofibrate can reduce oxidative stress in spontaneously hypertensive rats without up-regulating the activity of antioxidant enzymes, which may be related to the high expression of HMGCS2 protein.