佐剂关节炎大鼠滑膜血管新生与PTEN/PI3K/AKT信号传导通路的关系

Relations of synovial angiogenesis and PTEN/PI3K/AKT signaling pathway in rats with adjuvant arthritis

目的:观察佐剂关节炎大鼠滑膜PTEN/PI3K/AKT通路及缺氧诱导因子(HIF-1α)、血管内皮细胞生长因子(VEGF)表达,探讨类风湿关节炎血管新生的机制。方法:30只大鼠随机分成正常对照组和模型对照组,模型对照组采用弗氏完全佐剂建立佐剂关节炎大鼠模型。造模成功后第19天,采用酶联免疫吸附法检测大鼠HIF-1α、VEGF、微血管密度(MVD)的表达,采用Western Blotting检测滑膜PTEN、PI3K、AKT蛋白表达。结果:与正常对照组比较,模型对照组大鼠足跖肿胀度、关节炎指数升高,血清MVD、VEGF、HIF-1α表达及滑膜PI3K、AKT升高,PTEN降低。相关性分析显示,PI3K、HIF-1α与MVD呈正相关,VEGF、AKT与足趾肿胀度呈正相关,PTEN与关节炎指数呈负相关。HIF-1α与VEGF呈正相关,PI3K与AKT呈正相关,PTEN与PI3K、AKT、VEGF呈负相关。结论:佐剂关节炎大鼠滑膜PTEN/PI3K/AKT通路表达失调是引起滑膜血管新生的机制之一。

Objective： To observe the change of PTEN/PI3K/AKT pathway, hypoxia-inducible factor （HIF- 1α）, vascular endothelial growth factor （VEGF） in rats with adjuvant arthritis and to explore the mechanism of neovasculization in rheumatoid arthritis. Methods：Thirty rats were randomly divided into normal control group and model control group. The model control group were established the model of adjuvant arthritis using Freund＇s complete adjuvant. At 19 days after modeling,the expression of microvascular density （MVD）, HIF-1α, VEGF were detected by ELISA assay and PTEN, PI3K, AKT were detected by Werstern Blotting. Results： Compared with the normal control group, paw swelling, arthritic index were increased, and the expression of MVD, VEGF, HIF-1 α of serum, PI3K, AKT of synovial tissue were significantly increased, PTEN was significantly decreased in model control group. PI3K, HIF-1α were positively correlated with MVD ;VEGF, AKT were positively correlated with paw swelling; PTEN was negatively correlated with the arthritis index; HIF-1α was positively correlated with VEGF; PI3K was positively correlated with AKT, PTEN was negatively correlated with PI3K, AKT, VEGF. Conclusion ： Imbal- ance of PTEN/PI3K/AKT pathway in rats with adjuvant arthritis is one of the mechanisms of synovial neovasculization.