胡黄连苷Ⅱ对脑缺血再灌注大鼠神经损伤的保护作用研究

Neuroprotective effect of picrosideⅡon cerebral ischemia-reperfusion injury in rats

目的研究胡黄连苷Ⅱ对大鼠脑缺血再灌注损伤的保护作用。方法采用线栓法制作大鼠大脑中动脉闭塞再灌注(MCAO/R)模型,经尾静脉注射胡黄连苷Ⅱ10、30mg/kg,以银杏叶提取物注射液为阳性药。于缺血再灌注24h后进行神经功能评分和提高躯体摆动实验(EBST),观察病灶处病理学变化,测定脑匀浆上清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、还原型谷胱甘肽含量、一氧化氮合酶(NOS)活性等。结果与模型组比较,胡黄连苷Ⅱ治疗组神经功能评分和对侧旋转次数水平降低,差异有统计学意义(P<0.05或P<0.01);病理学研究显示病灶处皮质神经元肿胀坏死有所减轻;脑匀浆上清SOD活性和GSH含量明显升高,MDA含量显著降低(P<0.01);总NOS(T-NOS)、诱导型NOS(iNOS)、构建型NOS(cNOS)活性均明显降低,P<0.01或P<0.001。结论胡黄连苷Ⅱ可保护MCAO/R模型大鼠神经功能,该作用与胡黄连苷Ⅱ提高模型大鼠脑组织的抗氧化能力、减少脑缺血再灌注所致的氧化性损伤有关。

Objective To investigate the neuroprotective effects of picrosideⅡ on cerebral ischemia-reperfusion injury in rats. Methods Intraluminal thread methods were applied to establish the middle cerebral artery occlusion reperfusion model（MCAO/R） in rats. Picroside Ⅱ（10 and 30 mg/kg） was given through intravenous injection from trail vein,and so was the extract of Ginkgo biloba leaves injection （10mg/kg）, the positive drug. The neurological score and elevated body swing test（EBST）were taken at 24 h after ischemia-reperfusion. Then observed pathological changes in lesions, and determined the activity superoxide dismutase （SOD） and nitric oxide synthase （NOS） and content of malondialdehyde （MDA） and reduced glutathione（GSH） in brain homogenate supernatant. Results Compared with model group, the neurological score and the time of contralateral rotation of treatment group given picroside Ⅱ were lower and shorter, and the difference of these two groups was statistically significant（P0.05 or P0.01）. Pathology studies have shown that swelling and necrosis of cortical neurons in lesions have lessened. GSH content and SOD activity significantly increased（P0.01）, by contrary MDA content and NOS activity（which include these three subtypes T-NOS, cNOS iNOS）significantly decreased （P0.01 or P0.001）. Conclusion PicrosideⅡ remarkably improved the neural behavioral functions of model rats and reduces the pathological changes. What′s more, it could also improve the antioxidation capacity of brain tissue and reduce oxidation injury caused by cerebral ischemia-reperfusion.