摘要
[目的]探讨沙立芦单抗对类风湿性关节炎(RA)滑膜细胞增殖、凋亡的影响.[方法]体外培养人RA细胞系FLS细胞(RA-FLS细胞),随机分为空白对照组和沙立芦单抗低剂量组(加入2.5 mg/L沙立芦单抗溶液)、中剂量组(加入5.0 mg/L沙立芦单抗溶液)、高剂量组(加入10.0 mg/L沙立芦单抗溶液).采用CKK-8法检测各组RA-FLS细胞增殖抑制率;采用AnnexinV-FITC/PI双染法检测各组RA-FLS细胞凋亡率;采用蛋白免疫印迹法检测各组细胞兔抗细胞增殖相关核抗原(PCNA)、凋亡蛋白B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)及蛋白酪氨酸激酶Janus激酶1/转录活化蛋白3(JAK1/STAT3)通路蛋白(JAK1、p-JAK1、STAT3、p-STAT1蛋白)表达水平.[结果]与空白对照组相比,沙立芦单抗低剂量组、中剂量组、高剂量组RA-FLS细胞增殖抑制率升高(P<0.05),且呈剂量依赖性(P<0.05);与空白对照组相比,沙立芦单抗低剂量组、中剂量组、高剂量组RA-FLS细胞凋亡率升高(P<0.05),且呈剂量依赖性(P<0.05);与空白对照组比较,沙立芦单抗低剂量组、中剂量组、高剂量组RA-FLS细胞PCNA、Bcl-2蛋白降低(P<0.05),Bax蛋白升高(P<0.05),且呈剂量依赖性(P<0.05);与空白对照组比较,沙立芦单抗低剂量组、中剂量组、高剂量组RA-FLS细胞IL-6、p-JAK1/JAK1、p-STAT3/STAT3蛋白升高(均P<0.05),且呈剂量依赖性.[结论]沙立芦单抗可能通过抑制IL-6/JAK1/STAT3通路活化进而抑制RA-FLS细胞增殖,并诱导细胞凋亡,可为临床治疗RA提供一定参考.
【Objective】To investigate the effects of sarilumab on the proliferation and apoptosis of rheumatoid arthritis(RA)cells,and to analyze the related mechanisms.【Methods】Human RA cell line FLS cells(RA-FLS cells)were cultured in vitro and divided into the control group,the sarilumab low,medium and high dose groups(final concentration of 2.5 mg/L,5.0 mg/L and 10.0 mg/L,respectively).The proliferation inhibition rate of RA-FLS cells was detected by CKK-8 and the apoptosis rate of RA-FLS cells was detected by Annexin V-FITC/PI double staining.The expression of anti-proliferation related nuclear Antigen(PCNA),apoptosis protein B lymphocyte-2(Bcl-2),Bcl-2 related X protein(Bax)and protein tyrosine kinase of Janus kinase 1/STAT3 pathway protein(JAK1,p-JAK1,STAT3 and p-STAT1)was detected by Western blotting.【Results】The proliferation inhibition rate,apoptosis rate and expression levels of PCNA and Bcl-2 protein in RA-FLS cells from the sarilumab low,middle and high dose groups were higher than those in the control group(P<0.05),while the levels of Bax and p-JAK1/JAK1,p-STAT3/STAT3 were significantly lower than those in the control group(P<0.05).All of those dectections were in dose dependent manner(P<0.05).【Conclusion】Sarilumab may inhibit the proliferation of RA-FLS cells and induce apoptosis by inhibiting the activation of IL-6/JAK1/STAT3 pathway.
作者
王潇
王桂玲
刘彤
WANG Xiao;WANG Gui-ling;LIU Tong(Department of Spinal Cord Surgery,The Third Hospital of Shandong Province,Jinan Shandong 250031)
出处
《医学临床研究》
CAS
2023年第1期102-104,共3页
Journal of Clinical Research
关键词
关节炎
类风湿
抗体
单克隆
滑膜细胞
细胞增殖
细胞凋亡
Arthritis,Rheumatoid
Antibodies,Monoclonal
Synoviocytes
Cell Proliferation
Apoptosis
