补阳还五汤通过干预肠道菌群改善阿司匹林致消化道损伤作用及机制研究

Study on the effect and mechanism of Buyang Huanwu Decoction on improving aspirin induced gastrointestinal injury by intervention of intestinal microflora

关键词:  阿司匹林  消化道损伤  肠道菌群  补阳还五汤  抗血小板药物

Key words:  aspirin  digestive tract injury  intestinal flora  Buyang Huanwu Decoction  antiplatelet drugs

摘要:

[目的] 评价补阳还五汤的抗血小板效果并基于16SrDNA技术，从肠道菌群的角度探讨其对抗血小板药物所致消化道损伤的干预效果和作用机制。[方法] 将75只清洁级健康雄性SD大鼠随机分为对照组、模型组、补阳还五汤组、血府逐瘀汤组、双抗组，各组15只。对照组正常饲养，其余4组在阿司匹林基础上分别予相应药物灌胃处理，连续给药2周。检测血清花生四烯酸（AA）、血栓素B2（TXB2）、血小板膜糖蛋白Ⅱb/Ⅲa（GPⅡb/Ⅲa）水平；监测各组小鼠体质量变化、凝血时间，行便潜血实验，观察消化道黏膜病理组织切片；并提取大鼠粪便DNA进行16SrRNA测序并分析。[结果] 与模型组相比，补阳还五汤组AA、TXB2水平呈降低趋势，但差异无统计学意义（P>0.05）；与对照组相比，补阳还五汤组GPⅡb/Ⅲa水平显著降低（P<0.01）；补阳还五汤组大鼠便潜血阳性率最低（P<0.05），而且体外凝血时间、体质量增加量以及肠黏膜病理损伤程度均得到不同程度改善；此外，通过Alpha与Beta多样性分析发现，补阳还五汤可以在门水平和属水平改善消化道菌群的丰富度和多样性。[结论] 补阳还五汤具有抗血小板作用，可以显著降低GPⅡb/Ⅲa水平，并能改善阿司匹林导致的消化道损伤，其对消化道的保护作用可能与影响消化道菌群的丰富度和多样性、改善厚壁菌门与拟杆菌门比例、上调普氏菌属和乳杆菌属等菌属有关。

Abstract:

[Objective] To evaluate the antiplatelet effect of Buyang Huanwu Decoction and explore its intervention effect and mechanism of antiplatelet drug-induced gastrointestinal injury from the perspective of intestinal flora based on 16SrDNA technology. [Methods] The 75 clean grade healthy male SD rats were divided into control group,model group,Buyang Huanwu Decoction group,Xuefu Zhuyu Decoction group and Shuangkang group,with 15 rats in each group. The control group was fed normally,and the other four groups were given corresponding drugs by gavage on the basis of aspirin for 2 weeks. The levels of serum arachidonic acid(AA),thromboxane B2 (TXB2) and platelet membrane glycoprotein Ⅱb/Ⅲa(GPⅡb/Ⅲa) were measured. The body weight change,clotting time,fecal occult blood test and pathological sections of digestive tract mucosa were observed in each group. DNA from rat feces was extracted for 16SrRNA sequencing and analysis. [Results] Compared with the model group,the levels of AA and TXB2 in Buyang Huanwu Decoction group decreased,but the difference was not statistically significant(P>0.05). Compared with the control group,the level of GPⅡb/Ⅲa in the Buyang Huanwu Decoction group was significantly lower(P<0.01). The positive rate of fecal occult blood of rats in Buyang Huanwu Decoction group was the lowest(P<0.05). And the coagulation time in vitro,weight gain and pathological injury of intestinal mucosa were improved to varying degrees;In addition,according to the diversity analysis of Alpha and Beta,Buyang Huanwu Decoction can improve the abundance and diversity of digestive tract flora at the level of phylum and genus. [Conclusion] Buyang Huanwu Decoction has antiplatelet effect,can significantly reduce the level of GP Ⅱb/Ⅲa,and can improve the digestive tract injury caused by aspirin. Its protective effect on the digestive tract may be related to affecting the abundance and diversity of the digestive tract flora,improving the ratio of Thick-walled bacteria to Bacteroides,and up-regulating the genera of Platypiella and Lactobacillus.