Zhao Yeyu, Chen Yiran, Wang Zhimin, Peng Cheng, Li Quansheng, Wu Jin, Wang Linmin, Liu Dongwu, Yue Yue, Qing Qi, Sun Pengyuan, Liang Liang, Yu Huan, Ju Xing, Li Lue, Wang Enlong, Gao Mingli, Yu Jing, Ma Tieming
Department of Rheumatology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
School of Acupuncture, Moxibustion and Tuina, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Ann Transl Med. 2022 Feb;10(3):145. doi: 10.21037/atm-21-6822.
Based on the ASIC1a/NLRP3 signaling pathway, we explored the specific molecular mechanism of the pyroptosis of rheumatoid arthritis (RA) chondrocytes by the method of nourishing qi, nourishing yin, and dredging collaterals to provide new ideas for the treatment of this disease.
A total of 50 rats were divided into a normal group, model group, methotrexate group, Yiqi Yangyin Tongluo group, and combined group. Except for the normal control group, the other groups used Freund's complete adjuvant (FCA) to make RA rat model. The arthritis index and ankle joint swelling of rats in each group were recorded. HE staining and ELISA were used to assess the pathology of the ankle joint of each group of rats and the content of IL-1β and IL-18 in rat serum. Furthermore, immunofluorescence and qPCR methods were used to detect the protein and mRNA expression levels of NLRP3, caspase 1, ACS, and ASIC1a in the cartilage tissue of each group of rats.
Compared with the normal group, the right hind foot joint of the model group was significantly swollen, the levels of IL-18 and IL-1β in the serum of rats increased significantly, and the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes also increased significantly. Compared with the model group, the degree of ankle joint swelling and IL-18 and IL-1β content in rat serum in each medication group was significantly reduced, and the combined group showed the greatest reduction compared with the other groups. After 8 weeks of treatment, compared with the model group, the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes of each medication group were down-regulated. HE staining found that there were large numbers of infiltrating inflammatory cells and pannus in the joint tissue of the model group, while only a small amount of inflammatory cell infiltration and pannus was seen in the joint tissue of the rats in each treatment group.
The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of RA chondrocytes through the ASIC1a/NLRP3 signaling pathway.
基于ASIC1a/NLRP3信号通路，我们采用益气养阴通络法探讨类风湿关节炎（RA）软骨细胞焦亡的具体分子机制，为该病的治疗提供新思路。
将50只大鼠分为正常组、模型组、甲氨蝶呤组、益气养阴通络组和联合组。除正常对照组外，其余各组采用弗氏完全佐剂（FCA）制备RA大鼠模型。记录各组大鼠的关节炎指数和踝关节肿胀情况。采用HE染色和ELISA法评估各组大鼠踝关节病理及大鼠血清中IL-1β和IL-18含量。此外，采用免疫荧光和qPCR方法检测各组大鼠软骨组织中NLRP3、半胱天冬酶-1、ACS和ASIC1a的蛋白及mRNA表达水平。
与正常组相比，模型组右后足关节明显肿胀，大鼠血清中IL-18和IL-1β水平显著升高，软骨细胞中NLRP3、半胱天冬酶-1、ACS和ASIC1a的mRNA及蛋白水平也显著升高。与模型组相比，各用药组大鼠踝关节肿胀程度及血清中IL-18和IL-1β含量均显著降低，联合组降低幅度最大。治疗8周后，与模型组相比，各用药组软骨细胞中NLRP3、半胱天冬酶-1、ACS和ASIC1a的mRNA及蛋白水平均下调。HE染色发现，模型组关节组织中有大量炎性细胞浸润和血管翳，而各治疗组大鼠关节组织中仅见少量炎性细胞浸润和血管翳。
益气养阴通络法可通过ASIC1a/NLRP3信号通路减轻RA软骨细胞焦亡。
