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
Effects of Gubi Recipe on the PI3K/AKt Pathway and Synovial Tissue of Knee Joint in the Rats Model of Knee Osteoarthritis
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摘要: 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。Abstract: 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 recipe 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 improve the knee synovial membrane injury score of rats, effectively reduce the inflammatory reaction in knee synovial membrane. 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 lesions in the process, to some extent improve the pathology of knee osteoarthritis, the mechanism may be related to the intervention of PI3K/AKt pathway of knee osteoarthritis cartilage tissue of rat.