骨痹方对大鼠膝骨关节炎PI3K/AKt信号通路及组织形态学的影响

摘要

目的 探讨骨痹方对KOA大鼠软骨细胞PI3K/AKt信号通路及膝关节滑膜病理组织形态学的影响.方法 按照改良Hulth's法复制40只KOA大鼠模型随机分为5组:模型组、阳性药组(维固力组)、骨痹方高、中、低剂量组,每组8只,另假手术组(n=8)大鼠术中暴露前后交叉韧带后即可,正常组(n=8)大鼠无需任何处置.每日灌胃1次,共8周.8周后取各组大鼠患膝滑膜,观察其组织形态学变化;应用 Western blot 法检测膝关节软骨细胞 PI3K/AKt 信号通路 AKt 及其下游靶蛋白Bcl-2、Bax的表达.结果 模型组大鼠膝关节滑膜组织形态学检查评分比正常组显著增高(P<0.01);骨痹方中、高剂量组大鼠膝关节滑膜损伤评分较模型组均有所下降(P<0.05).模型组大鼠 AKt及下游靶蛋白 Bcl-2表达低于正常组,骨痹方高剂量组 AKt表达量显著高于正常组(P<0.01),骨痹方中剂量组 AKt 表达量与正常组接近;与模型组比较,骨痹方高剂量组AKt表达量及下游靶蛋白Bcl-2显著升高(P<0.01),Bax表达降低.结论 骨痹方可以有效地减少膝骨关节炎病变过程中软骨细胞的凋亡,一定程度地改善膝骨关节炎病理组织形态学,其作用机制可能与其干预 KOA 大鼠软骨细胞 PI3K/AKt 信号通路密切有关.%OBJECTIVE To study the effects of Gubi recipe on the PI3K/AKt pathway and synovial tissue of nnee joint in the rats model of knee osteoarthritis.METHODS SD rats(n=40)were duplicated by Hulth's technique and randomly divided into the model group,the Glucosamine Sulfate capsules group,the low dose group of Gubi recipe,the dose group of Gubi reci-pe and the high dose group of Gubi recipe.Also,the rats in the sham group(n=8)were exposed to the cruciate ligament after the operation,and the normal group(n=8)did not need any disposal.All rats were given the solution by filling the stomach for 8 weeks.8 weeks later,the the synovial membrane was taken from each rat for observing;Western blot technic of articular cartilage PI3K/AKt pathway AKt activation extent and detect the expression of Bcl-2 and Bax.RESULTS Gubi recipe can im-prove the knee synovial membrane injury score of rats,effectively reduce the inflammatory reaction in knee synovial mem-brane.The expression of AKt and downstream target protein Bcl-2 was lower than that of normal group,the expression level of AKt in the high dose group of Gubi recipe was much higher than that in the normal group(P<0.01),the expression level of AKt in the middle dose group was close to that in the normal group;compared with the model group,the expression of AKt and the downstream target protein Bcl-2 in the high dose group were significantly higher(P<0.01),and the expression of Bax was decreased.CONCLUSION Gubi recipe can effectively reduce the chondrocyte apoptosis of osteoarthritis of the knee le-sions in the process,to some extent improve the pathology of knee osteoarthritis,the mechanism may be related to the inter-vention of PI3K/AKt pathway of knee osteoarthritis cartilage tissue of rat.