微生态调节剂对肠道菌群失调类风湿关节炎大鼠的行为、免疫及病理学影响研究

Effects of microecological modulator on behavior,immunity and pathology in rats of rheumatoid arthritis with intestinal microecological imbalance

目的研究不同微生态调节剂对肠道菌群失调类风湿关节炎(rheumatoid arthritis,RA)大鼠的行为、免疫及病理学影响。方法在70只6周龄Wistar雌性大鼠中,随机选取10只为未处理(untreated control,UC)组,60只建立肠道菌群失调RA大鼠模型,分为阴性对照(negative control,NC)组、益生菌(probiotics,Pro)组、益生元(prebiotics,Pre)组、肠黏膜保护剂(intestinal mucosal protectant,IMP)组、合生素(synbiotics,SYN)组、合生素+肠黏膜保护剂(SYN+IMP)组,每组10只,分别给予等量生理盐水或微生态调节剂灌胃,持续28 d。观察大鼠一般状态、体质量变化,评估关节炎指数;记录各组血清炎症因子、辅助性T(helper T,Th)17细胞和调节性T(regulatory T,Treg)细胞比例及踝关节和滑膜组织的病理学改变。结果与UC组相比,NC组大鼠一般状态较差,体质量增长缓慢,关节炎指数增高(P<0.05);与NC组相比,各干预组大鼠一般状态及体质量增长逐渐恢复,关节炎指数降低,SYN+IMP组改善效果最佳(P<0.05)。与UC组相比,NC组血清炎症因子白介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α、转化生长因子-β(transforming growth factor-β,TGF-β)、IL-17和Th17细胞升高,IL-10和Treg细胞比例降低(P<0.05);与NC组相比,各干预组血清炎症因子水平、Th17细胞和Treg细胞比例均不同程度改善,SYN+IMP组最优,差异有统计学意义(P<0.05),Pro、Pre和IMP组差异无统计学意义(P>0.05)。与UC组相比,NC组大鼠血管翳、骨侵蚀形成,伴大量炎症细胞浸润;与NC组相比,各干预组大鼠关节病变减轻,炎症细胞减少,SYN+IMP组改善效果最佳。结论微生态调节剂可降低肠道菌群失调RA大鼠的关节炎指数,抑制血清炎症因子水平,纠正机体免疫失衡状态,减轻踝关节和滑膜组织病理学改变。

Objective To investigate the effects of different microecological modulators on behavior,immunity and pathology in rheumatoid arthritis(RA)rats with intestinal microecological imbalance.Methods Seventy six-week-old Wistar female rats were selected randomly,10 were in the untreated control(UC)group,sixty RA rats with intestinal microecological imbalance were divided into negative control(NC)group,probiotics(Pro)group,prebiotics(Pre)group,intestinal mucosal protective agent(IMP)group,synbiotics(probiotics+prebiotics,SYN)group,synbiotics+intestinal mucosal protective agent(SYN+IMP)group,10 rats in each group were given the corresponding amount of normal saline(UC and NC group)or microecological regulator intragastric administration for 28 days.The general status and body weight of rats in each group were observed and arthritis index was evaluated.Serum inflammatory factors,helper T(Th)17 cell and regulatory T(Treg)cell levels and pathological changes of ankle joint and synovial were observed in each group.Results Compared with UC group,NC group had poor general status,slow weight gain and increased arthritis index(P<0.05).Compared with NC group,the general status and weight gain of RA rats of all the intervention group gradually recovered,arthritis index decreased,and SYN+IMP group had the best improvement effect(P<0.05).Compared with UC group,the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,IL-17 and Th17 cells in NC group were significantly increased,while the levels of IL-10 and Treg cells were significantly decreased(P<0.05).Compared with NC group,the levels of serum inflammatory factors and Th17 cells and Treg cells in all intervention groups were improved in different degrees,and the SYN+IMP group was better than SYN group,which were better than Pro group,Pre group and IMP group,the differences were statistically significant(P<0.05).There was no significant difference between Pro group,Pre group and IMP group(P>0.05).Compared with UC group,the pathological changes of joints and synovium in NC group were serious,vascular pannus and bone erosion were formed,accompanied by a large number of inflammatory cell infiltration.Compared with NC group,the pathological changes of joints were alleviated,and the infiltration and aggregation of inflammatory cells in all intervention groups were reduced,and SYN+IMP group had the best improvement effect.Conclusion Different microecological modulators can reduce the arthritis index,inhibit the level of serum inflammatory factors,correct the immune imbalance and alleviate the histopathological changes of ankle joint and synovial membrane in RA rats with intestinal microecological imbalance.