扎里奴思方对气虚血瘀型脑缺血再灌注大鼠宏观表征、血液流变学及神经细胞凋亡相关机制的影响

目的:通过建立气虚血瘀型脑缺血再灌注大鼠模型,探讨回药扎里奴思方对气虚血瘀型脑缺血再灌注大鼠宏观表征、血液流变学及神经细胞凋亡等相关机制的影响。方法:将170只SD大鼠随机分为正常组,假手术组,模型组,尼莫地平组,扎里奴思方高、中、低剂量组(29.2,14.6,7.3 g·kg-1);正常组、假手术组各10只,其余各组根据时间点分为3,7 d组,每组15只;除正常组外,其余各组均采用饥饿、疲劳、寒湿、惊恐及高脂饮食等多因素制备气虚血瘀型大鼠模型,于4周证候模型完成,给予大鼠ig给药4 d(正常组、假手术组及模型组给予等体积的生理盐水),复制局灶性脑缺血(MCAO)再灌注模型,观察各组大鼠的神经精神状况、体重、进食、舌质变化及排便情况;心脏取血进行血液流变学检测;原位末端转移酶标记法(TUNEL)法检测脑组织皮质区神经细胞凋亡情况。结果:与正常组比较,假手术组通过宏观表征的观察及血液流变学指标的检测,出现明显的气虚血瘀证候,说明证候模型复制成功;与假手术组比较,模型组在气虚血瘀的基础上出现明显的偏瘫样症状,神经功能评分显著升高(P0.01),全血黏度明显升高(P0.05,P0.01),红细胞变形性指数明显降低(P0.05)及红细胞聚集性指数和红细胞压积显著升高(P0.01),大鼠神经细胞凋亡较显著(P0.01);与模型组比较,扎里奴思方可显著改善气虚血瘀型脑缺血再灌注大鼠宏观表征,降低模型大鼠全血黏度、血红细胞压积、红细胞聚集性,提高红细胞变形性,并抑制脑组织细胞凋亡,尤以扎里奴思方高剂量7 d组作用显著(P0.05,P0.01)。结论:扎里奴思方对气虚血瘀型脑缺血再灌注大鼠损伤具有良好的保护作用,其机制可能与改善模型大鼠血液流变学、抑制脑组织神经细胞凋亡密切相关。

Effect of Zhali Nusi Fang on Macroscopic Syndrome, Hemorheological Parameters and Brain Cell Apoptosis in Cerebral Ischemia Reperfusion Model of Rats with Qi Deficiency and Blood Stasis

Objective: To observe the effects of Zhali Nusi Fang on macroscopic syndrome, hemorheological parameters and brain cell apoptosis in cerebral ischemia reperfusion of rats with Qi deficiency and blood stasis. Method: Totally 170 rats were randomly divided into normal group, sham operation group, model group, nimodipine group, high, medium and low-dose Zhali Nusi Fang groups (29.2,14.6,7.3 g·kg^-1). Expect for normal group and sham operation group, all of the remaining groups were subdivided into 3-day and 7-day groups, with 15 in each group. Except for normal group, all of the remaining groups were included into the Qi deficiency and blood stasis mode by means of combined factors of hunger, tiredness, cold dampness, panic and high fat diet for 4 weeks. Drugs were given to the rats through intragastric administration for 4 days. The middle cerebral artery occlusion (MCAO) model was duplicated to observe the rats'' nerve mental status, changes in body weight, feeding, tongue and defecation. Blood was collected for hemorheology detection; Tunel method was used to detect apoptosis of brain cortex. Result: Compared with the normal group, according to macroscopic observation and detection of blood rheology indexes in the sham operation group, the syndrome of qi deficiency and blood stasis syndrome was observed successfully. Compared with the sham operation group, the model group showed obvious hemiplegia symptoms in addition Qi deficiency blood stasis symptoms, and neurological scores of rats in model group significantly increased (P<0.01), whole blood viscosity significantly rose (P < 0.05, P < 0.01), and changes in blood rheology indexes were significantly reduced (P<0.05), blood cell aggregation index and hematocrit significantly increased (P<0.01), and nerve cell apoptosis was obvious (P<0.01). Compared with the model group, Zhali Nusi Fang can significantly improve cerebral ischemia and reperfusion rats with Qi deficiency and blood stasis, and decrease whole blood viscosity, hematokrit, blood cell aggregation, improve the deformation of red blood cells, and inhibit the apoptosis of brain cells, especially in the high-dose 7d group. Conclusion: Zhali Nusi Fang has a good protective effect on cerebral ischemia and reperfusion in rats with Qi deficiency and blood stasis, its mechanism may be closely related to improvement of blood rheology and inhibition of brain nerve cell apoptosis of model rats.