作 者 ：李浩,姚明江,徐立,刘剑刚,赵文明
期 刊 ：中国中药杂志 2009年 34卷 20期 页码：2622.
关键词：认知功能障碍；细胞凋亡；海马；还脑益聪方；TUNEL技术；
Keywords:cognitive impairment, apoptosis, hippocampus, Huannao Yicong decoction, TUNEL technique,
摘 要 ：目的：观察还脑益聪方对复合因素所致大鼠认知功能障碍模型认知功能、海马区细胞凋亡情况及相关基因表达的干预作用。方法：SD大鼠60只，按随机方法分为中高组、中低组、阳性组、模型组及空白组。空白组每日皮下注射等量生理盐水，共10周，并饲喂普通饲料至第10周末；其他各组每日皮下注射D-半乳糖50 mg·kg-1体重，共10周，并于第5周开始同时给予半高脂饲料饲喂。第7周开始，中药高、低剂量组均给予还脑益聪方混悬液0.01 mL·g-1体重灌胃（用药量分别为生药14 g·kg-1体重及生药7 g·kg-1体重）；阳性药对照组给予盐酸多奈哌齐混悬液0.01 mL·g-1体重灌胃（用药量为0.4 mg·kg-1体重）；模型与空白对照组均给予等量蒸馏水；灌胃每日1次至第10周末。观察各组动物行为学的变化海马区细胞凋亡情况及凋亡相关蛋白Bcl-2， Bax的变化。结果：水迷宫试验显示，模型组潜伏期明显延长，穿台次数明显减少，和空白组比较有显著差异（P<0.05，P<0.01），中高组及阳性组穿台次数与模型组比较，有显著性差异（P<0.05，P<0.01）；模型组海马凋亡细胞数量明显增加，和空白组比较有显著差异（P<0.01），中高组、中低组及阳性组均可减少海马细胞凋亡数量，提高Bcl-2与Bax的比值，差异有统计学意义（P<0.01）。结论：还脑益聪方能改善认知功能障碍大鼠学习记忆能力，通过抑制海马细胞凋亡，调节相关基因表达，加速细胞修复，保护损伤脑组织作用，可能是其临床效应的部分途径。
Abstract:Objective: To observe the intervention effects of Huannao Yicong decoction on cognitive function and apoptosis and expression of relative regulative gene of Hippocampus in cognitive impairment rats induced by complex factors. Method: 60 SD rats were divided randomly into Huannao Yicong decoction high-dose group (HHG)， Huannao Yicong decoction low-dose group (HLG)， positive control group (PCG)， model control group (MCG) and blank control group (BCG). Rats in the BCG were received daily hypodermic injection of tales doses of normal sodium for 10 weeks with normal feeder. Rats in other groups were received daily hypodermic injection of D-galactose with the concentration of 50 mg·kg-1 for 10 weeks， from the 5th week on， half fat feeder were fed until the end of the 10th week. From the 7th on， rats in HHG were administered with 0.01 mL·g-1 Huannao Yicong decoction suspension by gavage (crude drug 14 g·kg-1). Rats in LHG were administered with 0.01 mL·g-1 Huannao Yicong decoction suspension by gavage (crude drug 7 g·kg-1). Rats in PCG were administered with 0.01 mL·g-1 hydrochloricdonepezil suspension by gavage (0.4 mg·kg-1). Rats in MCG and BCG were administered with 0.01 mL·g-1distilled water by gavage， intragastric administration was given daily until the end of the 10th week. The behaviors of the rats were observed by morris water maze， the apoptosis and expression of relative regulative gene of hippocampus were measured. Result: The morris water maze indicated that compared with the BCG， the platform locating latency of rats in the MCG was longer and the frequency of swimming through the platform was fewer（P<0.05， P<0.01）， compared with the MCG， there was significant difference on the frequency of swimming through the platform in the HHG and PCG（P<0.05， P<0.01）. The number of apoptosis cells in the MCG was more than that in the BCG， the difference was significant（P<0.01）， the number of apoptosis cells in the HHG， HLG and PCG was reduced and the ratio of Bcl-2 and Bax was increased（P<0.01）. Conclusion: Huannao Yicong decoction could improve the learning and memory functions of cognitive impairment rats， inhibit the apoptosis of cells in hippocampus， regulate the expression of relative gene， accelerate the repairing of cells， protect the impaired brain tissue， and these may be part of the channels of clinical effects.