莫诺苷对脑缺血再灌注大鼠皮层肝细胞生长因子及血管性血友病因子表达的影响
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国家自然科学基金(81373994;81173575);"重大新药创制"科技重大专项(2012ZX09102201-106)。


Effects of morroniside on the expression of the HGF and vWF in peri-infarct cortex after cerebral ischemia-reperfusion in rats
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    摘要:

    目的 研究莫诺苷对脑缺血再灌注7 d大鼠患侧皮层肝细胞生长因子(hepatocyte growth factor,HGF)及血管性血友病因子(von willebrand factor,vWF)表达的影响。方法 25只健康成年雄性Sprague-Dawley(SD)大鼠采用改良Zealonga线栓法制备大鼠大脑中动脉阻塞(middle cerebral artery occlusion, MCAO)模型,术后随机分为假手术组、模型组、莫诺苷小剂量组、中剂量组及大剂量组,每组5只。造模后3 h按照30, 90, 270 mg/kg剂量每天一次灌胃给予莫诺苷。免疫印迹法和免疫荧光法分别检测莫诺苷对脑缺血再灌注7 d大鼠患侧皮层HGF及vWF表达的影响。结果 脑缺血再灌注7 d后,免疫印迹法显示,与假手术组相比,模型组HGF蛋白表达显著升高(P < 0.01);同模型组相比,莫诺苷给药组(30 mg/kg、90 mg/kg、270 mg/kg)HGF蛋白表达水平均显著升高(P < 0.05,P < 0.01,P < 0.001)。免疫荧光法显示,与假手术组相比,模型组vWF表达显著升高(P < 0.001);同模型组相比,莫诺苷中、大剂量组(90 mg/kg、270 mg/kg)vWF表达显著升高(P < 0.01,P < 0.001)。结论 莫诺苷可以上调HGF及vWF在脑内的表达,促进局灶性脑缺血大鼠血管新生。

    Abstract:

    Objective To study the effects of morroniside on the expression of the HGF and vWF of the ischemic ipsilateral cortex 7 days after ischemia reperfusion. Methods 25 male Sprague-Dawley rats were subjected to MCAO model with modified Zea Longa's method, then randomly divided into sham group (n=5), ischmia group (n=5), and morroniside groups (low, medium, and high dosage groups, n=5). Morroniside were then administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of HGF and vWF of the ischemic ipsilateral cortex were detected by western blotting and Immunofluorescence 7 days after ischemia-reperfusion. Results Compared with the sham group, the expression of HGF in ischemia group increased significantly (P < 0.01) 7 days after MCAO. Compared with the ischemia group, the expression of HGF in the morroniside groups (30 mg/kg, 90mg/kg, 270 mg/kg) showed significant increased (P < 0.05, P < 0.01, P < 0.001). Compared with the sham group, the expression of vWF in ischemia group increased significantly (P < 0.001). Compared with the ischemia group, the expression of vWF in the morroniside groups (90 mg/kg, 270 mg/kg) showed significant increased (P < 0.01, P < 0.001). Conclusion Morroniside could increase the expression of HGF and vWF in the ischemic ipsilateral cortex, romoting the process of angiogenesis in focal cerebral ischemia rat.

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魏仁平,孙芳玲,刘婷婷,程华,艾厚喜,郭德玉,田欣,祝自新,王宇峰,郑文荣,王文.莫诺苷对脑缺血再灌注大鼠皮层肝细胞生长因子及血管性血友病因子表达的影响[J].中国比较医学杂志,2016,26(3):24~28.

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