阿利吉仑对大鼠膝骨关节炎血清及软骨炎性因子的影响

Effect of aliskirenon on inflammatory cytokine expression in serum and cartilage of knee osteoarthritis in rat

[目的]探讨阿利吉仑干预对膝骨关节炎大鼠软骨组织的保护作用和血清中炎性因子的影响。[方法]30只SD大鼠随机分为假手术组、模型组、治疗组,每组10只。假手术组仅切开关节囊,而模型组和治疗组按改良后Hulth法建立骨性关节炎模型,前两组灌胃给予生理盐水,而治疗组给予阿利吉仑。建模成功后,取大鼠血样测量IL-1、IL-6的含量;取膝关节行Masson染色、番红花染色;采用RT-qPCR检测各组软骨组织中Runx2、TNF-αmRNA,采用Western blot检测软骨IL-1、IL-6、Runx2、TNF-α蛋白表达水平。[结果]与假手术组相比,模型组大鼠血清中IL-1和IL-6浓度明显增加(P<0.05),而治疗组较模型组明显下降(P<0.05)。Masson染色结果发现,模型组大鼠软骨细胞较假手术组明显肥大,而治疗组情况明显改善;番红花染色显示,与假手术组相比,模型组大鼠组织切片中软骨细胞面积明显减少,而治疗组的染色面积明显减少。模型组大鼠软骨组织中Runx2和TNF-αmRNA表达水平明显上升(P<0.05),而治疗组较模型组明显下降(P<0.05)。与假手术组相比,模型组大鼠软骨组织中IL-1、IL-6、Runx2和TNF-α蛋白表达水平明显上升(P<0.05),而治疗组较模型组明显下降(P<0.05)。[结论]阿利吉仑能够有效抑制膝骨关节炎大鼠软骨组织的破坏,显著降低膝骨关节炎大鼠血清和软骨中的炎性因子水平。

[Objective]To explore the effect of aliskiren on inflammatory cytokine expression in serum and cartilage of knee osteoarthritis in rat.[Methods]A total of 30 SD rates were randomly divided into the sham operation group,the model group and the treatment group,with 10 animals in each group.The rats in the sham group underwent arthrotomy only,while those in the model group and treatment group were created osteoarthritis model by modified Hulth method.The animals in the sham group and model group were fed normal saline,whereas those in the treatment group were fed aliskiren intragastrically.After successful modeling,the blood sample was harvested for assessment of IL-1 and IL-6 by ELISA,and the cartilage specimens were obtained for morphological observation by Masson and Saffron O stains,assay of Runx2 and TNF-αby RT-qPCR and the IL-1,IL-6,Runx2 and TNF-αprotein by western blot.[Results]Compared with the sham group,the serum levels of IL-1 and IL-6 in the model group increased significantly(P<0.05),while them in the treatment group proved significantly lower than the model group(P<0.05).Masson staining showed that the chondrocyte in model group was significantly hypertrophic than that of the sham group,while the condition in treatment group was significantly improved.Saffron O staining revealed that the area of chondrocyte in the model group was significantly reduced compared with the sham group,while that in treatment group was significantly greater than the model group.The expression levels of Runx2 and TNF-αmRNA in cartilage tissue of the model group increased significantly(P<0.05),but those were significantly lower in the treatment group than the model group(P<0.05).The western blot showed that the expression of IL-1,IL-6,Runx2 and TNF-αin cartilage of model group was significantly higher than that of the sham group(P<0.05),while the expression levels in the treatment group significantly decreased compared with the model group(P<0.05).[Conclusion]Aliskiren does effectively inhibit destruction of cartilage tissue and expression of inflammatory cytokines in serum and cartilage of knee osteoarthritis in rat.