益智清心方对自然衰老大鼠学习记忆能力和肠道菌群的影响

Effects of Yizhi Qingxin Formula on Learning and Memory Ability and Intestinal Flora of Naturally Aged Rats

目的观察益智清心方对自然衰老大鼠学习记忆能力和肠道菌群的影响。方法采用Morris水迷宫筛选出认知功能障碍的自然衰老大鼠。按照分层随机的方法分为模型组、盐酸多奈哌齐组(0.45 mg/kg)、益智清心方低剂量组(0.3 mg/kg)、益智清心方高剂量组(0.6 mg/kg),每组10只,并选用10只认知功能正常的自然衰老大鼠作为空白对照组,分别给予相应的药物或相同体积的蒸馏水灌胃8周。通过Morris水迷宫测评大鼠的空间学习记忆能力;采用16S rDNA生物信息技术分析肠道菌群结构。结果与空白组比较,模型组大鼠逃避潜伏期延长,在原平台象限活动路程比降低(P<0.05,P<0.01)。与模型组比较,盐酸多奈哌齐组、益智清心方组的逃避潜伏期均缩短(P<0.01),益智清心方组在原平台象限活动路程比均增加(P<0.01);益智清心方组OTU指数、Chaol指数和进化距离指数均降低,覆盖度指数升高(P<0.05,P<0.01)。与模型组比较,盐酸多奈哌齐组未检测到蓝藻菌;益智清心方组肠道菌群群落丰度、多样性及结构都发生了显著改变,特别是降低蓝藻细菌的丰度、下调厚壁菌门/拟杆菌门相对丰度的比例,促进变形菌门和放线菌门富集。结论益智清心方能够提高自然衰老大鼠的空间学习记忆能力,其机制可能与调节肠道菌群结构,保持肠道微生态平衡相关。

Objective To investigate the effects of Yizhi Qingxin Formula(YZQXF)on learning and memory ability and intestinal flora of naturally aged rats. Methods The natural aged rats with cognitive impairment were screened by Morris water maze(MWM). According to the method of stratified random,rats were divided into model group,donepezil hydrochloride group(0.45 mg/kg),YZQXF low-dose group(0.3 mg/kg),and YZQXF high-dose group(0.6 mg/kg),10 in each group. Meanwhile,10 naturally aged rats with normal cognitive function were selected as control group. The corresponding drugs or distilled water of equal volume were given intragastrically for 8 weeks. The learning and cognitive ability was detected by MWM,and the intestinal flora was analyzed by 16 S ribosomal DNA(16 S rDNA). Results Compared with the control group,the escape latency of model group was prolonged,and the swimming distance ratio in the platform quadrant was decreased(P<0.05,P<0.01). Compared with the model group,the escape latency of donepezil hydrochloride group and YZQXF groups shortened(P<0.01),and the swimming distance ratio of YZQXF groups in the platform quadrant increased(P<0.01);the OTU index,Chaol index and Phylogenetic diversity index of YZQXF groups decreased,while the Good coverage index increased(P<0.05,P<0.01). Compared with the model group,no cyanobacteria was detected in the donepezil hydrochloride group. The abundance,diversity and structure of intestinal flora in YZQXF groups were significantly changed,especially the abundance of cyanobacteria decreased,the relative abundance ratio of firmicutes/bacteroidetes down-regulated,and the proteobacteria and actinobacteria were enrichment. Conclusion YZQXF can improve spatial learning and memory ability of naturally aged rats,and its mechanism may be related to regulating intestinal flora and maintaining intestinal microecological balance.