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目的:通过观察大鼠脑出血后神经细胞凋亡与缺氧诱导因子-1α(HIF-1α)、蛋白酶激活受体-1(PAR-1)表达的动态变化及蛭龙活血通瘀胶囊的干预作用,探讨蛭龙活血通瘀胶囊可能的脑保护作用。方法:将大鼠随机分为假手术组、模型组、蛭龙活血通瘀胶囊低、中、高剂量组。采用自体血注入法制备脑出血大鼠模型。采用TUNEL法测定凋亡细胞的表达,免疫组化法测定HIF-1α、PAR-1蛋白的表达。结果:与模型组比较,蛭龙活血通瘀胶囊低、中、高剂量组的凋亡细胞与PAR-1蛋白表达明显下降,而HIF-1α蛋白的表达明显升高,差异有统计学意义(P<0.01)。与低剂量组比较,中、高剂量组各时间点的凋亡细胞与PAR-1蛋白表达均明显下降,而HIF-1α蛋白的表达明显升高,差异有统计学意义(P<0.01)。结论:蛭龙活血通瘀胶囊能明显抑制PAR-1活化,促进HIF-1α表达,抑制细胞凋亡,对脑出血大鼠具有明显的脑保护作用,且存在一定量效关系。
OBJECTIVE: To observe the dynamic changes of apoptosis and the expression of hypoxia-inducible factor-1α (HIF-1α) and PAR-1 (-1) after intracerebral hemorrhage in rats and the intervention of Zhi Long Huoxue Tongyu Capsule Role, to explore the possible brain protection of Hirudo Huoxue Tongyu capsule. Methods: The rats were randomly divided into sham-operated group, model group, and Zhudilong Huoxuetongyu Capsule low, medium and high dose groups. Preparation of intracerebral hemorrhage rat model by autologous blood injection. The apoptotic cells were detected by TUNEL method and the expressions of HIF-1α and PAR-1 protein were detected by immunohistochemistry. Results: Compared with the model group, the expression of PAR-1 and protein of apoptotic cells decreased significantly in low, medium and high dose of Zhi Long Huoxue Tongyu Capsules, while the expression of HIF-1α protein was significantly increased P <0.01). Compared with the low dose group, the expression of PAR-1 protein and apoptosis cells in the medium and high dose groups were significantly decreased at each time point, while the expression of HIF-1α protein was significantly increased (P <0.01). Conclusion: The Zhi Long Huoxue Tongyu Capsule can significantly inhibit the activation of PAR-1, promote the expression of HIF-1α and inhibit the apoptosis of the cells. It has a significant protective effect on cerebral hemorrhage in rats, and there is a certain dose-effect relationship.