痴复康方改善PSCI大鼠的空间学习和记忆能力及其作用机制

Improvement of Chifukang Recipe on Spatial Learning and Memory Ability of PSCI Rats and the Mechanism

目的研究痴复康方对卒中后认知障碍(PSCI)大鼠的影响并探讨其机制。方法对48只大鼠双侧颈总动脉结扎制作PSCI模型,分为正常组、模型组、尼莫地平组及痴复康方低、中、高剂量组。通过Morris水迷宫实验测试大鼠的空间学习和记忆能力,病理观察海马组织改变,qPCR法检测海马组织N-甲基-D-天门冬氨酸受体NR2B亚基(NR2B)、钙调蛋白激酶Ⅱ(CaMKⅡ)、高迁移率族蛋白B1 (HMGB-1)、转化生长因子β1 (TGF-β1)、 Smad7 mRNA的表达。结果与正常组相比,模型组大鼠逃避潜伏期延长,穿越原平台次数减少,原平台象限停留时间缩短(P均<0.01);大鼠海马组织神经元减少,细胞排列松散、不规则,部分可见核仁消失、锥体细胞减少;NR2B、 CaMKⅡ、 mRNA表达减少,HMGB-1、 TGF-β1、 Smad7 mRNA表达增加(P均<0.01)。与模型组相比,痴复康方各剂量组随着剂量增加,大鼠逃避潜伏期缩短,穿越原平台次数增加,原平台象限停留时间延长(P均<0.01);大鼠海马组织神经元增加,坏死细胞减少,细胞核固缩减少,正常神经元增加,细胞轮廓清晰,排列整齐;NR2B、 CaMKⅡmRNA表达增加,HMGB-1、 TGF-β1、 Smad7 mRNA表达减少(P均<0.01),以高剂量组改善最明显。结论痴复康方能提高PSCI大鼠模型的空间学习和记忆能力,其机制与减少海马神经元坏死,上调海马组织NR2B、CaMKⅡmRNA表达,下调HMGB-1、 TGF-β1、 Smad7 mRNA表达有关。

Objective To study the influence of Chifukang recipe on post-stroke cognitive impairment(PSCI)rats and to explore the mechanism.Methods PSCI model was established by ligating bilateral common carotid arteries in 48 rats.They were divided into normal group,model group,nimodipine group and low-dose group,middle-dose group and high-dose group of Chifukang.The spatial learning and memory ability of rats was tested by Morris water maze experiment.Pathological sections were used to observe the changes in hippocampal tissue,and qPCR was used to detect the expressions of NR2B,CaMKⅡ,HMGB-1,TGF-β1 and Smad7 mRNA.Results Compared with the normal group,the escape latency of the model group prolonged,the times of crossing the original platform decreased,and the quadrant residence time of original platform shortened(P<0.01);The rats'hippocampal tissue neurons decreased,cells were arranged loosely and irregularly,and some of them could be seen disappeared nucleoli and decreased pyramidal cells;The expressions of NR2B,CaMKⅡand mRNA decreased,and the expressions of HMGB-1,TGF-β1 and Smad7 mRNA increased(P<0.01).Compared with the model group,with the increase of the dose,the escape latency of each dose group of Chifukang recipe shortened,the times of crossing the original platform increased,and the quadrant residence time of original platform prolonged(P<0.01);The rats'hippocampal tissue neurons increased,the necrotic cells decreased,the nucleus shrinkage decreased,the normal neurons increased,and the cell outlines were clear and neatly arranged;The expressions of NR2B and CaMKⅡmRNA increased,and the expressions of HMGB-1,TGF-β1 and Smad7 mRNA decreased(P<0.01);The improvement was most obvious in the high-dose group.Conclusions Chifukang recipe can improve the spatial learning and memory ability of PSCI rat models.Its mechanism is related to reducing hippocampal neuron necrosis,up-regulating the expression of NR2B and CaMKⅡmRNA in hippocampus,and down-regulating the expression of HMGB-1,TGF-β1 and Smad7 mRNA.