桃红四物汤对脑缺血再灌注损伤大鼠脑内血管新生及PI3K/AKT信号转导通路的影响

目的:探讨桃红四物汤对脑缺血再灌注损伤大鼠脑内血管新生及PI3K/AKT信号转导通路的影响.方法:将健康的雄性SD大鼠分为假手术组、模型组、华佗再造丸组(2.0 g/kg)和桃红四物汤高、中、低剂量组(2.1 g/kg、1.4 g/kg、0.7 g/kg),采用改良的线栓法复制大鼠脑缺血再灌注损伤模型,术后连续给药7 d.采用Zea longa方法对各组大鼠进行神经功能缺损评分,采用免疫组织化学法检测各组大鼠脑缺血皮质区微血管密度(MVD)和血管内皮细胞生长因子(VEGF)表达水平,采用Western blot法检测各组大鼠脑组织中蛋白激酶B(AKT)和磷酸化蛋白激酶B(p-AKT)蛋白表达水平.结果:假手术组大鼠未见神经功能缺损,华佗再造丸组和桃红四物汤高、中、低剂量组神经功能缺损评分均低于模型组(P<0.05~P<0.01),桃红四物汤高剂量组神经功能缺损评分均低于华佗再造丸组、桃红四物汤中和低剂量组(P<0.05~P<0.01);假手术组MVD、VEGF均显著低于模型组(P<0.01),桃红四物汤高、中剂量组和华佗再造丸组MVD和p-AKT均高于模型组,桃红四五汤高剂量组VEGF显著高于模型组(P<0.01);桃红四物汤高剂量组MVD、p-AKT均高于华佗再造丸组和桃红四物汤中、低剂量组(P<0.05~P<0.01),桃红四物汤高剂量组VEGF高于低剂量组(P<0.05),各组AKT表达水平差异无统计学意义(P>0.05).结论:桃红四物汤对脑缺血再灌注损伤大鼠模型有显著药效,其作用机制可能为通过激活PI3K/AKT信号转导通路而促进脑缺血部位的血管新生,使脑缺血再灌注损伤大鼠的损伤的神经功能得到恢复.

Effect of Taohongsiwu decoction on the angiogenesis and PI3K/AKT signal pathway in brain tissue of rats with cerebral ischemia reperfusion injury

Objective:To explore the effects of Taohongsiwu decoction on the angiogenesis and PI3K/AKT signal pathway in brain tissue of rats with cerebral ischemia reperfusion injury ( CIRI ) . Methods:Adult male SD rats were randomly divided into the sham group,model group,Huatuozaizao pill group(2. 0 g/kg),and high,middle and low dose of Taohongsiwu decoction groups(2. 1 g/kg, 1. 4 g/kg and 0. 7 g/kg). The CIRI model rats were established using the modified MCAO,and successively infused for 7 days. The nerve function scoring,microvessel density(MVD) and vascular endothelial growth factor(VEGF),and levels of AKT and p-AKT in brain tissue of all groups were investigated using the Zea longa, immunohistochemistry and Western blot, respectively. Results:The nerve function injury in sham group were not found,the scores of the nerve dysfunction in Huatuozaizao pill group,and high,middle and low dose of Taohongsiwu decoction groups were significantly lower than that in model group(P<0. 05 to P<0. 01). the score of the nerve dysfunction in high dose of Taohongsiwu decoction group was significantly lower than that in Huatuozaizao pill group,and middle and low dose of Taohongsiwu decoction groups(P<0. 05 to P<0. 01). The levels of MVD and VEGF in sham group were significantly lower than those in model group(P <0. 01),the levels of MVD in Huatuozaizao pill group and high,middle dose of Taohongsiwu decoction groups were significantly higher than those in model group(P<0. 01),and the level of VEGF in high dose of Taohongsiwu decoction group was significantly higher than that in model group(P <0. 01). The levels of MVD and p-AKT in high dose of Taohongsiwu decoction group were higher than those in Huatuozaizao pill group, and middle and low dose of Taohongsiwu decoction groups(P <0. 05 to P <0. 01),the level of VEGF in high dose of Taohongsiwu decoction group was lower than that in low dose of Taohongsiwu decoction group(P<0. 05),and the differences of the levels of AKT between each group were not statistically significant(P>0. 05). Conclusions:Taohongsiwu decoction in treating the rats with CIRI has significant effects, the mechanism of which may be involved in promoting the angiogenesis and recovering the nerve function by activating PI3K/AKT signal pathway in ischemic site of brain.