miR-155靶向调节PIK3R1对类风湿关节炎大鼠模型PI3K/Akt/mTOR信号通路的影响  

Effect of miR-155 on the PI3K/Akt/mTOR signaling pathway in rheumatoid arthritis rats by targeting PIK3R1

作　　者：吴焘[1] 张国秋[1] 李超[1] 张兰涛 WU Tao;ZHANG Guoqiu;LI Chao;ZHANG Lantao(Department of Joint Surgery,the Affiliated Hospital of Qinghai University,Xi’ning 810012,China)

机构地区：[1]青海大学附属医院关节外科,青海西宁810012

出　　处：《中国骨质疏松杂志》2022年第11期1593-1598,共6页Chinese Journal of Osteoporosis

基　　金：青海省科技计划项目(2018-ZJ-763)。

摘　　要：目的 探讨miR-155靶向调节PIK3R1对类风湿关节炎(rheumatoid arthritis, RA)大鼠PI3K/Akt/mTOR信号通路的影响。方法 SD大鼠随机分为对照组、模型组、miR-155 agomir组、miR-155 antagomir组、miR-155阴性对照组,诱导RA模型,分组处理后,观察关节症状,检测关节炎指数及后足趾容积;HE染色观察大鼠关节组织病理形态;使用试剂盒检测大鼠关节组织炎性因子IL-6、IL-17及IL-18水平;免疫印迹检测大鼠关节组织PI3K/Akt/mTOR信号通路蛋白表达;qRT-PCR实验检测大鼠关节组织miR-155及PIK3R1 mRNA水平;双荧光素酶报告基因实验检测miR-155对PIK3R1的靶向调控作用。结果 与对照组比较,模型组大鼠关节炎症状明显,关节炎指数、后足趾容积、关节组织炎性因子IL-6、IL-17及IL-18水平、关节组织p-PI3K/PI3K、p-Akt/Akt及p-mTOR/mTOR水平、关节组织miR-155水平明显升高(P<0.05),PIK3R1 mRNA水平明显降低(P<0.05)。与模型组、miR-155阴性对照组比较,miR-155 antagomir组大鼠上述指标得到明显改善(P<0.05);miR-155 agomir组与miR-155 antagomir组趋势相反(P<0.05)。结论 miR-155可靶向下调PIK3R1的表达,激活PI3K/Akt/mTOR信号,加重RA大鼠关节炎症损伤,下调miR-155表达,可抑制PI3K/Akt/mTOR信号激活及炎症反应发生发展,改善关节炎症状。Objective To investigate the effect of miR-155 on the PI3 K/Akt/mTOR signaling pathway in rheumatoid arthritis(RA) rats by targeting PIK3 R1. Methods SD rats were randomly divided into control group, model group, miR-155 agomir group, miR-155 antagomir group, and miR-155 negative control group. RA model was induced in rats. After treatment with drugs, joint symptoms were observed. The arthritis index and hind toe volume were measured. HE staining was used to observe the pathological morphology of rat joint tissues. Levels of inflammatory factors IL-6, IL-17, and IL-18 in rat joint tissues was detected with the kits. PI3 K/Akt/mTOR signaling pathway protein expression in rat joint tissues was detected with Western blotting. qRT-PCR experiment was used to detect the levels of miR-155 and PIK3 R1 mRNA in rat joint tissues. Dual luciferase reporter gene experiment was used to detect the targeted regulation of miR-155 on PIK3 R1. Results Compared to those in the control group, the symptoms of arthritis in the model group were obvious, the arthritis index, hind toe volume, joint tissue inflammatory factors IL-6, IL-17, and IL-18 levels, joint tissue p-PI3 K/PI3 K, p-Akt/Akt, and p-mTOR/mTOR levels, joint tissue miR-155 level increased significantly(P<0.05), and the PIK3 R1 mRNA level reduced significantly(P<0.05). Compared to those in the model group and the miR-155 negative control group, the above indexes of miR-155 antagomir group were significantly improved(P<0.05). The trend in miR-155 agomir group was opposite to that in miR-155 antagomir group(P<0.05). Conclusion MiR-155 targets to down-regulate the expression of PIK3 R1, to activate PI3 K/Akt/mTOR signal, to aggravate the joint damage of RA rats, and to down-regulate the expression of miR-155. It inhibits the activation of PI3 K/Akt/mTOR signal and the occurrence and development of inflammation, and relieves the symptoms of arthritis.

关 键 词：MIR-155 PIK3R1 类风湿关节炎 PI3K/AKT/MTOR 大鼠 

分 类 号：R593.22[医药卫生—内科学]