远志汤对慢性脑低灌注大鼠认知功能及海马凋亡蛋白的影响

Effects of Yuanzhi decoction on cognitive function and apoptosis-related protein in hippocampus of rats with chronic cerebral hypoperfusion

目的观察远志汤对慢性脑低灌注大鼠空间学习记忆能力及海马凋亡蛋白的影响。方法采用永久结扎大鼠双侧颈总动脉法造模。将42只SD大鼠采用数字表法随机分为正常对照组,模型组,假手术组,远志汤高、中、低剂量组[20、10、5 g/(kg·d)]及阳性药物对照组[盐酸多奈哌齐0.52 mg/(kg·d)],每组各6只,分别灌胃给药,1次/d,给药4周。通过Morris水迷宫定位航行实验及空间探索实验,观察远志汤对慢性脑低灌注大鼠空间学习记忆能力的影响;通过免疫荧光染色法检测远志汤对慢性脑低灌注大鼠海马凋亡相关蛋白B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2相关X蛋白抗体(Bcl-2 associated X protein,Bax)及半胱氨酸天冬氨酸特异性蛋白酶3(cysteinyl aspartate specific proteinase-3,Caspase-3)表达的影响。结果模型组大鼠较对照组和假手术组的逃避潜伏期和搜索距离明显延长(P<0.01),在原平台所在象限的搜索时间明显缩短(P<0.01)。而远志汤各剂量干预均可明显缩短大鼠的逃避潜伏期和搜索距离(P<0.01),并延长在原平台所在象限的搜索时间(P<0.01)。模型组大鼠海马Bax和Caspase-3的表达较对照组和假手术组增加,差异有统计学意义(P<0.05),Bcl-2则显著下降,差异有统计学意义(P<0.01)。而远志汤高、中剂量组干预均可明显减少Bax和Caspase-3的表达(P<0.05),增加Bcl-2的表达(P<0.05)。结论远志汤可能通过调节海马凋亡相关蛋白Bcl-2、Bax和Caspase-3的表达以改善慢性脑低灌注大鼠的认知功能。

Objective To observe the effects of Yuanzhi decoction on spatial learning and memory ability and apoptosis-related protein in the hippocampus of rats with chronic cerebral hypoperfusion.Methods A rat model was developed with with ligating the bilateral common carotid arteries permanently.A total of 42 SD rats were divided into 7 groups according to the digital random method:control,model,sham,Yuanzhi decoction high[20 g/(kg·d)],medium[10 g/(kg·d)]and low[5 g/(kg·d)]dose intervention group,and the positive drug control group[donepezil hydrochloride 0.52 mg/(kg·d)](n=6 in each group).The rats were treated with intragastric administration once a day for 4 weeks.The Morris water maze positioning navigation experiment and space exploration experiment were used to evaluate the spatial learning and memory ability in rats.Immunofluorescence staining was used to examine the expression of apoptosis-related proteins B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3)in the hippocampus of rats.Results Compared with the control group and the sham group,the escape latency and search distance of the model group were significantly longer(P<0.01),and the search time in the quadrant of the original platform was significantly shorter(P<0.01).The high,medium and low dose of Yuanzhi decoction intervention can significantly shorten the escape latency and search distance(P<0.01),and prolong the search time in the quadrant of the original platform(P<0.01).The expression of Bax and Caspase-3 in the hippocampus of the model group were significantly increased compared with the control group and the sham group(P<0.05 or P<0.01),and Bcl-2 was significantly decreased(P<0.01).The intervention of high and medium dose of Yuanzhi decoction can significantly reduce the expression of Bax and Caspase-3(P<0.05)and increase the expression of Bcl-2(P<0.05 or P<0.01).Conclusion Yuanzhi decoction could regulate the expression of apoptosis-related proteins Bcl-2,Bax and Caspase-3 in hippocampus and improve cognitive function of rats with chronic cerebral hypoperfusion.