目的:研究骨关节炎(OA)大鼠模型软骨组织中脂酰肌醇3激酶( phosphatidylinositol 3 kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路功能与细胞凋亡的相关性。方法:选择清洁级雄性Wistar大鼠作为实验动物,并随机分为OA模型组和对照组；采用木瓜蛋白酶溶液与L-半胱氨酸关节腔内注射的方式建立OA模型。造模后第4周和第8周时,测定关节软骨中PI3K/AKT信号分子、炎症介质、细胞凋亡标志分子、细胞自噬标志分子的表达量。结果:OA组大鼠关节软骨组织中p-PI3K、p-AKT的表达量显著低于对照组；OA组大鼠关节软骨组织中白介素(IL)-1β、IL-6、IL-17、IL-18、eIF4E、Bax、Caspase-3、mTOR、Beclin1、Atg5、Atg7的表达量显著高于对照组,且与p-PI3K、p-AKT的表达量呈负相关,Bcl-2的表达量显著低于对照组且与p-PI3K、p-AKT的表达量呈正相关。结论:骨关节炎大鼠模型软骨组织中PI3K/AKT信号通路功能的抑制能够促进软骨细胞的凋亡和自噬。
Objective: To study the relationship between PI3K/AKT signaling pathway and apoptosis in cartilage tissue of rats with osteoarthritis (OA). Methods: The clean male Wistar rats were selected as experimental animals and randomly divided into OA model group and control group. The OA model was established by intra-articular injection of papain solution and L-cysteine. Fourth weeks and eighth weeks after model establishment, the expression of PI3K/AKT signaling molecules, inflammatory mediators, apoptosis marker molecules and autophagy marker molecules in articular cartilage were determined. Results: p-PI3K and p-AKT expression in articular cartilage of OA group were significantly lower than those of control group; IL-1β, IL-6, IL-17, IL-18, eIF4E, Bax, Caspase-3, mTOR, Beclin1, Atg5 and Atg7 expression in articular cartilage of OA group were significantly higher than those of control group and negatively correlated with p-PI3K and p-AKT expression while Bcl-2 expression in articular cartilage of OA group was significantly lower than that of control group and positively correlated with p-PI3K and p-AKT expression. Conclusions: The inhibition of PI3K/AKT signaling pathway in cartilage tissue of OA rat model can promote chondrocyte apoptosis and autophagy.