摘要
目的研究止痉散治疗类风湿关节炎(rheumatoid arthritis,RA)的新机制及安全性。方法本研究采用牛Ⅱ型胶原两次免疫诱导法造小鼠关节炎(collagen induced arthritis,CIA)模型,将造模成功小鼠随机分为正常对照组、模型组,甲氨蝶呤组和止痉散组,每日灌胃给药,记录小鼠体重,足爪关节的肿胀程度,并采集小鼠结肠、直肠和盲肠区段的粪便,利用二代测序方法,检测止痉散对小鼠肠道菌群的影响,同时对各脏器进行病理检查。利用ICR小鼠最大给药剂量(16 g/kg)急性毒性实验和人等效给药量(0.18 g/kg)亚急性毒性试验检测ZJS安全性。结果止痉散能够显著缓解小鼠关节肿胀,降低关节炎评分,降低关节部位IL-6和IL-2的表达,减少破骨细胞的数量。测序结果表明,止痉散显著降低直肠部位肠道菌群的Chao1指数和shannon指数,而在结肠、盲肠部位无明显变化。在门水平,止痉散升高直肠、盲肠部位拟杆菌门、放线菌门丰度,降低直肠、盲肠部位厚壁菌门,大肠杆菌门,变形菌门丰度;在属水平上,止痉散降低直肠与盲肠部位螺杆菌、毛螺菌、理研菌、另支菌属丰度,升高乳杆菌、拟杆菌属丰度。在止痉散急性毒性实验过程中,与正常组相比,止痉散组的脏器病理及血生化指标无显著性差异。结论止痉散能够增加直肠和盲肠部位有益菌群、降低肠道有害菌,恢复肠道微生物稳态环境从而改善类风湿关节炎小鼠的症状,且在止痉散的用药过程中无明显毒副作用。
Objective:To study the new mechanism and safety of Antispasmodic Powder in the treatment of rheumatoid arthritis(RA).Methods:The mouse model of collagen induced arthritis(CIA)was constructed by double immune induction of bovine type II collagen.The successfully constructed mice were randomly divided into normal control group,model group,methotrexate group and antispasmodic powder group.The mice were given daily intragastric administration,and the body weight and swelling degree of paw joint were recorded.The feces of colon,rectum and cecum of the mice were collected,and the effect of antispasmodic powder on intestinal microflora of the mice was detected by the second-generation sequencing method and the pathological examination of each organ was performed.The maximum dose of ICR in mice(16 g/kg)and equivalent dose in humans(0.18 g/kg)were used to test the safety of ZJS.Results:Antispasmodic powder could significantly relieve the joint swelling,reduce the arthritis score,reduce the expression of IL-6 and IL-2,and decrease the number of osteoclasts.The sequencing results showed that the Chao1 index and Shannon index of intestinal flora in the rectum were decreased significantly,but there was no significant change in the colon and cecum.At the phylum level,antispasmodic powder increased the abundance of bacteroidetes and actinomyces in the rectum and cecum,and decreased the abundance of firmicutes,escherichia coli and proteobacteria in the rectum and cecum.At the generic level,antispasmodic powder decreased the abundance of helicobacter,lachnospira,rikenella and mycobacterium in the rectum and cecum,and increased the abundance of lactobacillus and bacteroides.In the acute toxicity test of antispasmodic powder,the organ pathology and blood biochemical indexes of the antispasmodic powder group showed no significant difference compared with the normal group.Conclusion:Antispasmodic powder can increase the beneficial bacteria community in rectum and cecum,reduce the harmful bacteria in intestinal tract,restore the homeo
作者
王志衡
高杨
林聃
朱立忠
苏克雷
胡春萍
叶娟
王大为
WANG Zhi-heng;GAO Yang;LIN Dan;ZHU Li-zhong;SU Ke-lei;HU Chun-ping;YE Juan;WANG Da-wei(The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Traditional Chinese Medicine,Nanjing 210028,China;Jiangsu Institute of Traditional Chinese Medicine,Nanjing 210028,China)
出处
《云南中医中药杂志》
2023年第5期84-93,共10页
Yunnan Journal of Traditional Chinese Medicine and Materia Medica
基金
江苏省中医药科技发展计划项目(YB201928,YB2020016)
江苏省中医药研究院自主科研重点项目(BM2018-2019003)。
关键词
止痉散
类风湿关节炎
肠道菌群
Antispasmodic Powder
Rheumatoid Arthritis
Intestinal Flora
