电针改善慢性脑低灌注大鼠空间学习记忆能力和海马IL-6/JAK2/STAT3的信号调节

目的:观察电针调节慢性脑低灌注(chronic cerebral hypoperfusion,CCH)对大鼠海马JAK2/STAT3通路和炎症反应的影响,探讨电针减轻CCH所致空间学习记忆能力障碍的作用机制。方法:将成年SD雄性大鼠随机分为假手术组、模型组和电针组(n=10),行改良永久性双侧颈总动脉结扎术造模,电针组采用2/15 Hz频率刺激(30 min/d,持续4周)大鼠百会和大椎穴,其余2组动物进行平衡处理。采用Morris水迷宫实验和激光多普勒血流仪评估及检测大鼠的空间学习记忆能力和局部脑血流量(regional cerebral blood flow,r CBF);采用ELISA、RTPCR与Western blot法分别检测大鼠海马组织中炎性因子白细胞介素6(IL-6)和IL-1β浓度,海马JAK2和STAT3的mRNA表达及其磷酸化蛋白含量;HE染色观察海马组织的病理变化。结果:电针组大鼠r CBF、各时点平均逃避潜伏期和原平台象限停留时间均较模型组动物有明显改善(P0.01或P0.05)。电针组大鼠海马组织中IL-1β与模型组相比显著降低(P0.05),而IL-6的含量有显著升高(P0.05),海马JAK2和STAT3的mRNA表达及pJAK2和p-STAT3蛋白含量也均比模型组明显升高(P0.05),海马CA1区神经细胞损伤减轻。结论:电针可通过调节IL-6/JAK2/STAT3信号通路抑制炎症反应,从而减轻海马神经细胞损伤和认知障碍。

Electroacupuncture improves spatial learning and memory ability of rats with chronic cerebral hypoperfusion and signal regulation of hippocampal IL-6/JAK2/STAT3

AIM:To observe the effect of electroacupuncture (EA) on the inflammatory response and hippocampal JAK2/STAT3 signaling pathway in the rats with chronic cerebral hypoperfusion (CCH), and to explore the mechanism of EA attenuating the spatial learning and memory impairment induced by CCH. METHODS:Adult male Sprague-Dawley rats were randomly divided into sham group, model group and EA group (n=10). Modified permanent bilateral common carotid artery occlusion was used to establish animal model. The rats in EA group were stimulated at "Baihui" and "Dazhui" acupoints by 2/15 Hz frequency (30 min/d for 4 weeks), while the rats in the other 2 groups received balanced treatment. The spatial learning and memory ability and regional cerebral blood flow (rCBF) were detected by the methods of Morris water maze and laser Doppler flowmetry. The concentrations of interleukin (IL)-6 and IL-1β, the mRNA expression of JAK2 and STAT3, and the phosphorylated JAK2 and STAT3 protein levels in the hippocampus were determined by ELISA, RT-PCR and Western blot. The pathological changes of the hippocampus were observed with HE staining. RESULTS:In EA group, the rCBF, the average escape latency at every time point, and the original platform quadrant residence time were better than those in model group (P<0.01 or P<0.05). The level of IL-1β in EA group was significantly lower than that in model group (P<0.05), and the level of IL-6 was significantly increased (P<0.05). The mRNA expression of JAK2 and STAT3, and the protein levels of p-JAK2 and p-STAT3 in EA group were significantly higher than those in model group (P<0.05). The impairment of nerve cells in the hippocampal CA1 region was reduced. CONCLUSION:Electroacupuncture inhibits inflammatory response, and alleviates the hippocampal damage and the cognitive disorder by regulating IL-6/JAK2/STAT3 signaling pathways.