抗氧化剂PZ51对卒中易感型自发性高血压大鼠脑保护作用的探讨

The protective effect of antioxidant PZ51 on the brain of stroke-prone spontaneously hypertensive rat

目的探讨抗氧化剂PZ51对卒中易感型自发性高血压大鼠(SHRsp)高血压发展的慢性过程中的脑保护作用。方法22只SHRsp大鼠随机分为PZ51组和对照组,每组各11只,灌胃治疗6周。用分光光度计测大脑皮质匀浆丙二醛(MDA)、一氧化氮(NO)浓度;Westernblot检测大脑皮质内皮型一氧化氮合酶(eNOS)、神经元型一氧化氮合酶(nNOS)和诱导型一氧化氮合酶(iNOS)的蛋白表达;光镜检测颈动脉内膜中层厚度(IMT)。结果与对照组比较,PZ51组显著降低了大脑皮质匀浆MDA浓度[(2.09±0.62)nmolmg蛋白vs(4.11±0.45)nmolmg蛋白,P<0.001]和NO浓度[(0.82±0.19)μmolmg蛋白vs(1.24±0.28)μmolmg蛋白,P<0.001];PZ51抑制大脑皮质iNOS蛋白表达(P<0.01),对eNOS和nNOS无影响;光镜检查示PZ51组颈动脉IMT显著降低。结论PZ51显著降低了SHRsp大脑皮质MDA和NO浓度;抑制iNOS蛋白表达;降低了颈动脉IMT,从而发挥对SHRsp的脑保护作用。

Objective To investigate the protective effect of PZ51 on the brain of stroke-prone spontaneously hypertensive rat （SHRsp） during the chronic process of hypertension. Methods Twenty-two SHRsp of 8 weeks old were randomized into PZ51group and control group treated by gavage medication for six weeks. The levels of nitric oxide （NO） and malonaldehyde （MDA） in the cerebral cortex homogenate were measured by spectrophotometry. Endothelial nitric oxide synthase （eNOS）, neuronal nitric oxide synthase （nNOS） and inducible nitric oxide synthase （iNOS） protein expression were assayed by western blot. The intima-media thickness （IMT） of carotid artery was also measured. Results Compared with control group, PZ51decreased the levels of MDA [ （2.09±0.62） vs （4.11± 0.45） nmol/mg prot, P 〈 0. 001 ] and NO [ （0.82 ± 0.19） vs（1.24±0.28） μmol/mg prot, P 〈0.001] and iNOS protein expression （ P 〈0.01） in cerebral cortex significantly, but had no effect on eNOS and nNOS protein. PZ51 administration also decreased the IMT of carotid artery [（69.85±5.47） vs （76.60±6.53）μm] significantly. Conclusion PZ51 decreased lipid peroxidation of cerebral cortex, decreased NO level of cortex by inhibiting iNOS protein expression, and decreased IMT of carotid artery. These changes have been shown to have protective effect on the cerebral cortex of SHRsp.