摘要
为深入阐明正清风痛宁缓释片对膝骨关节炎治疗效果及作用机制,该研究采用0.2 mL的40 g·L^(-1)木瓜蛋白酶构建膝骨关节炎模型,造模成功后随机将大鼠分为模型组、正清风痛宁缓释片高剂量组、正清风痛宁缓释片低剂量组、塞来昔布组,持续给药4周且测定大鼠膝关节直径的变化。采用苏木精-伊红染色和番红固绿染色来观察SD大鼠膝关节组织的病理学情况。通过检测大鼠血浆中白细胞介素(IL)-1β和IL-6的含量初步评价正清风痛宁缓释片对膝骨关节炎大鼠的治疗作用。基于非靶向代谢组学技术和16S rRNA技术联合测定大鼠内源性小分子物质和肠道菌群的变化,找出潜在的生物标志物。结果表明,正清风痛宁缓释片可改善膝骨关节炎大鼠膝关节肿胀直径,改善软骨组织病理损伤并降低大鼠血浆中IL-1β和IL-6的含量。代谢组学分析筛选出22个与正清风痛宁缓释片调节效应相关的潜在生物标志物,包括5-羟色胺、皮质酮、甲基丙二酸等生物标志物,其主要涉及色氨酸代谢、维生素K代谢、类固醇合成等8条代谢通路。肠道菌群结果表明模型组肠道菌群多样性下降,给药后肠道菌群多样性增加且肠道菌群微生态得以改善。显著性差异菌有Lachnospiraceae_NK4A136_group、Helicobacter、Lactobacillus、Bacteroides、Parabacteroides。联合分析结果表明22个生物标志物与5类菌属存在一定关联性。以上结果说明正清风痛宁缓释片可改善膝关节组织形态结构、降低血浆炎症因子水平、调节肠道菌群多样性、平衡类固醇合成、维生素K代谢和色氨酸代谢等代谢通路发挥对膝骨关节炎的治疗作用。
In order to elucidate the therapeutic effect and mechanism of action of Zhengqing Fengtongning Sustainedrelease Tablets on knee osteoarthritis,this study created a knee osteoarthritis model using 2%papain and randomly divided the rats into the model group,high-dose and low-dose groups of Zhengqing Fengtongning Sustained-release Tablets,and celecoxib group.All groups were given the drug for four weeks,with the diameter of their knee joint being measured during this period.Hematoxylin-eosin staining and Senna solid green staining were utilized to observe the pathology of knee joint tissue in SD rats.The initial therapeutic impact of Zhengqing Fengtongning Sustained-release Tablets on knee osteoarthritis in rats was assessed by monitoring the levels of interleukin-1β(IL-1β)and interleukin-6(IL-6)in the plasma.Using a combination of non-targeted metabolomics and 16S rRNA techniques,researchers determined the variations in endogenous molecules and intestinal flora in rats and identified potential biomarkers. The results showed that Zhengqing FengtongningSustained-release Tablets improved the diameter of knee joint swelling, ameliorated the pathological damage of cartilagetissue, and reduced the plasma levels of IL-1β and IL-6 in rats with knee osteoarthritis. Metabolomics analysis identified 22potential biomarkers associated with the modulatory effects of Zhengqing Fengtongning Sustained-release Tablets, including5-hydroxytryptamine, corticosterone, methylmalonic acid, and other biomarkers, which were mainly involved i n eightmetabolic pathways, including tryptophan metabolism, vitamin K metabolism, steroid synthesis, and so on. The results ofintestinal flora showed a decrease in the diversity of intestinal flora in the model group, an increase in the diversity ofintestinal flora, and an improvement in the microecology of intestinal flora. Significant differences were found inLachnospiraceae_NK4A136_group, Helicobacter, Lactobacillus, Bacteroides, and Parabacteroides. Finally, the results of thecombined analysis showed that 22 biomarkers were correlated with five genera. The above results indicate that ZhengqingFengtongning Sustained-release Tablets can improve the tissue morphology and structure of knee joints, reduce the level ofplasma inflammatory factors, regulate the diversity of intestinal flora, and balance the metabolic pathways of steroidsynthesis, vitamin K metabolism, and tryptophan metabolism to exert a therapeutic effect on knee osteoarthritis.
作者
林青霞
聂春梅
车润莉
戎宽
陈林
黄建华
LIN Qing-xia;NIE Chun-mei;CHE Run-li;RONG Kuan;CHEN Lin;HUANG Jian-hua(Hunan University of Chinese Medicine,Changsha 410208,China;Hunan Academy of Chinese Medicine,Changsha 410013,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第23期6417-6428,共12页
China Journal of Chinese Materia Medica
基金
湖南省自然科学基金项目(2022JJ50047,2022JJ40239)。
关键词
代谢组学
肠道菌群
膝骨关节炎
正清风痛宁缓释片
metabolomics
intestinal flora
knee osteoarthritis
Zhengqing Fengtongning Sustained-release Tablets
