目的：研究不同剂量黄连素对实验性脑出血(intracerebral hemorrhage，ICH)大鼠脑水肿与神经功能的影响，并初步探讨其作用机制。方法：实验共分为假手术组(Sham组)，脑出血组(ICH组)，药物低(Ber-10组)、中(Ber-20组)、高剂量组(Ber-40组)，每组10只，除假手术组采用注射胶原酶的方法建立实验性脑出血大鼠模型，药物低、中、高剂量组分别给予黄连素10，20或40 mg/kg灌胃，每天1次，共给药28 d；对各组大鼠进行神经功能缺损评分，干湿重法测定脑含水量，Tunel法检测血肿周围脑组织细胞凋亡数，Western印迹法检测Cleaved cas-3，Cleaved cas-9，线粒体与胞浆中cyto-c的蛋白表达水平。结果：与脑出血组大鼠相比，采用黄连素给药后大鼠的神经功能缺损评分明显上升(P<0.05)，脑含水量明显下降(P<0.05)；血肿周围脑组织细胞凋亡数显著降低(P<0.05)，Cleaved cas-3和Cleaved cas-9的蛋白表达，线粒体中cyto-c的蛋白表达明显上升(P<0.05)而胞浆中cyto-c的蛋白表达明显下降(P<0.05) 。结论：黄连素具有改善实验性脑出血大鼠神经功能缺损以及保护脑细胞的作用，可能与黄连素抑制线粒体凋亡通路有关。
Effect of berberine on cerebral edema and neurological function in intracerebral hemorrhage rats
Objective: To investigate the effects of Berberine on cerebral edema and neurological function in experimental intracerebral hemorrhage (ICH) rats and to explore the underlying mechanisms. Methods: Rats were randomly divided into five groups: sham group, ICH group, ICH rats treated with low, medium or high dose of Berberine group. ICH model was induced by injection of collagenase, and ICH rats were received Berberine by gavage once a day at dose of 10, 20 or 40 mg/kg, respectively. After 28-day treatment, the grade of neurological function was scored, the water content of brain was measured, the apoptotic cells in pre-hematoma area were detected with TUNEL staining, and the protein expression of Cleaved cas-3, Cleaved cas-9 and the release of cytochrome c from mitochondria to cytoplasm were determined by Western blot. Results: Compared with the ICH group, neurological function improved significantly and the brain water content decreased, as accompanied with the reduced number of apoptotic cells in pre-hematoma area. Moreover, the protein expression of Cleaved cas-3, Cleaved cas-9 and the release of cytochrome c from mitochondria to cytoplasm were dramatically inhibited after berberine treatment. Conclusion: Berberine protects against ICH-induced the impairment of neurological function through inhibition mitochondria-dependent intrinsic apoptosis pathway.