毛冬青总皂苷提高血瘀大鼠脑缺血耐受的作用机制

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目的:研究毛冬青总皂苷提高血瘀大鼠脑缺血耐受模型的作用机制,为中药毛冬青的新用提供实验依据。方法:采用大鼠连续注射地塞米松复制血瘀模型。给予相应的药物,连续灌服7d,于第7天给药后1h,阻断双侧颈总动脉血流10min,恢复灌注72h后,颈内动脉线栓法致左大脑中动脉栓塞2h,再灌注24h。复制大鼠脑缺血耐受模型。取血测全血黏度;断头取左脑,测定ATP酶、总超氧化物歧化酶(T-SOD)活力,HE染色观察海马区组织病理变化,免疫组化法观察Bcl-2、Bax阳性的表达情况。结果:缺血耐受组及缺血再灌注损伤组大鼠全血黏度明显升高、ATPase及T-SOD活力显著下降(P<0.01)、Bax阳性表达显著增加(P<0.01),大鼠血瘀合并脑缺血耐受模型复制成功。与缺血再灌注损伤组比较,缺血耐受组动物全血流变值升高,T-SOD及ATPase活力增强,动物脑组织的病理损伤程度明显减轻。与缺血耐受组比较,各剂量毛冬青总皂苷能显著或明显改善血瘀大鼠的全血黏度,增强ATPase、T-SOD活力及Bcl-2阳性细胞的表达,降低Bax阳性表达,对脑神经细胞的损伤有明显的保护作用。结论:毛冬青总皂苷能从改善血液循环、改善能量代谢、诱导内源性抗氧化物活性增强、增强抗凋亡效应、减轻神经细胞损伤等方面实现提高脑缺血耐受的作用。 Objective: To study the mechanism of action of Mao dongqing total saponins in improving cerebral ischemia tolerance model of blood stasis rats, and to provide experimental basis for the new use of Mao Dongqing. Methods: Rats were injected with dexamethasone for blood stasis model. Given the corresponding drugs, continuous dosing 7d, on the first day after administration of 1h, blocking bilateral common carotid artery flow for 10min, 72h after reperfusion, internal carotid artery occlusion of the middle cerebral artery occlusion caused by 2h, and then Perfusion 24h. Rat model of cerebral ischemic tolerance was replicated. Blood samples were taken for determination of the whole blood viscosity. The left brain was taken for decapitation. The activities of ATPase and total superoxide dismutase (T-SOD) were measured. The histopathological changes in hippocampus were observed by HE staining. The expressions of Bcl-2 and Bax were observed by immunohistochemistry The expression of the situation. Results: The whole blood viscosity, the activity of ATPase and T-SOD in ischemic tolerance group and ischemia-reperfusion injury group were significantly decreased (P <0.01), the expression of Bax was significantly increased (P <0.01) Blood stasis with cerebral ischemic tolerance model was successfully replicated. Compared with the ischemia-reperfusion injury group, the whole blood rheology of ischemic tolerance group increased, the activity of T-SOD and ATPase increased, and the pathological damage of the brain tissue of animals was significantly reduced. Compared with the ischemic tolerance group, total saponin at each dose could significantly or significantly improve the whole blood viscosity of blood stasis rats, increase the activity of ATPase, T-SOD and the expression of Bcl-2 positive cells, and decrease the expression of Bax Injury of brain nerve cells have obvious protective effect. Conclusion: Total saponins of Mao dongqing can improve cerebral ischemia tolerance by improving blood circulation, improving energy metabolism, enhancing the activity of endogenous antioxidants, enhancing the anti-apoptotic effect and reducing the damage of nerve cells.
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