基于缺氧诱导因子及PI3K-AKT-mTOR信号通路诱导佐剂关节炎滑膜血管新生的实验观察  

Experimental observation of PI3K-AKT-mTOR signaling pathway and HIF-1a in synovial angiogenesis rats with adjuvant arthritis

作　　者：张晓军[1] 刘健 万磊 黄传兵 黄旦[1] 齐亚军[1] 

机构地区：[1]安徽中医药大学,合肥230038 [2]安徽中医药大学第一附属医院

出　　处：《中国临床保健杂志》2018年第1期84-87,共4页Chinese Journal of Clinical Healthcare

基　　金：国家自然基金青年项目(81403388);安徽省科技厅项目(1604f0804030);安徽省自然科学基金(1508085QH159);安徽省高校自然科学基金重点项目(KJ2017A281)

摘　　要：目的观察佐剂关节炎大鼠滑膜血管PI3K-AKT-m TOR信号通路及缺氧诱导因子(HIF-1α)、血管内皮细胞生长因子(VEGF-A)、滑膜微血管密度(MVD)表达。方法采用随机数字表法将30只大鼠均分成两组:正常组,模型组,模型组采用弗氏完全佐剂建立佐剂关节炎模型。造模成功后19 d,采用免疫组织化学法检测滑膜血管MVD表达,酶联免疫吸附法检测血清白介素-6(IL-6)、白介素-10(IL-10)、HIF-1α、VEGF-A表达,免疫印迹检测滑膜血管PI3K-AKT-m TOR通路蛋白表达。结果与正常组比较,模型组大鼠关节炎及MVD计数升高,血清IL-6、VEGF、HIF-1α和滑膜血管磷脂酰肌醇3激酶(PI3K)、蛋白激酶B1(AKT1)、p-AKT1、哺乳动物雷帕霉素靶向蛋白(m TOR)表达显著升高,IL-10降低(P<0.05或P<0.01)。结论 PI3K-AKT-m TOR通路过度激活可能是引起滑膜血管新生的原因之一。Objective To observe the change of PI3 K-AKT-m TOR signaling pathway,hypoxia inducible factor(HIF-1α),vascular endothelial growth factor(VEGF) and microvessel density(MVD) of synovial tissue in rats of adjuvant arthritis. Methods 30 rats were randomly divided into two groups,normal control and model control group. The model control group were established by using Freund' s complete adjuvant. The expression of microvascular density(MVD) were detected using immunohistochemical ninteen days after the modeling. Interleukin(IL)-6,IL-10,HIF-1αand VEGF were detected by enzyme-linked immunosorbent assay. PI3 K,AKT1,p-AKT1,m TOR protein were detected by Werstern blotting. Results Compared with normal control group,paw swelling,arthritic index were increased and serum IL-6,VEGF,HIF-1α of serum MVD,PI3 K,AKT1,p-AKT1,m TOR of synovial vascular were significantly increased in model control group. There were positive correlation between HIF-1α and MVD,VEGF-A,PI3 K and MVD,p-AKT1 protein,and PI3 K,p-AKT1 were positively correlated with VEGF-Α,HIF-1α,m TOR were positively correlated with VEGFA,PI3 K,AKT( P < 0. 05). Conclusion Excessive activation of PI3 K-AKT-m TOR pathway might be involved in the synovial angiogenesis in rats with adjuvant arthritis.

关 键 词：关节炎 实验性 血管生成诱导剂 信号传导 缺氧诱导因子1 Α亚基 大鼠 Sprague-Dawley 

分 类 号：R684.3[医药卫生—骨科学]