匹多莫德对实验性免疫球蛋白A肾病大鼠肾功能及炎症反应的影响

目的:探讨匹多莫德对IgA肾病(IgAN)模型大鼠肾功能的影响,并进一步研究该作用是否与其对炎症反应的抑制相关。方法:36只SD大鼠分别分为对照组、IgAN模型组、IgAN模型+匹多莫德治疗组和IgAN模型+强的松治疗组,每组9只大鼠。采用连续口服牛丙种球蛋白(BGG)8周后尾静脉注射BGG 3 d的方法制作IgAN大鼠模型。在IgAN模型成功后,连续用药4周。治疗结束后,利用自动分析仪检测尿蛋白、血清肌酐和血尿素氮含量,通过免疫荧光法观察IgA在肾组织内的沉积,用RT-qPCR法检测肾组织中肾纤维化标志物转化生长因子β1(TGF-β1)和纤连蛋白1(fibronectin 1)的mRNA表达水平,RT-qPCR和Western blot法检测肾组织中促炎细胞因子白细胞介素1β(IL-1β)和IL-6的表达。结果:各组大鼠的体重并没有明显差异。在IgAN模型大鼠中,尿蛋白、血清肌酐和血尿素氮均显著增加(P<0.01)。匹多莫德治疗可部分逆转以上生化指标的升高,减少IgA在肾组织内的沉积,抑制肾组织中肾纤维化标志物TGF-β1和fibronectin 1的mRNA表达水平,抑制肾组织中炎性细胞因子IL-1β和IL-6 mRNA和蛋白表达。结论:匹多莫德可能通过抑制炎症反应减轻IgAN大鼠的病理进程。

Effect of pidotimod on renal function and inflammatory response in rat IgA nephropathy model

AIM: To explore the effect of pidotimod on the renal function in IgA nephropathy(IgAN) rat model, and to further study whether this effect is related to the inhibition of inflammatory response. METHODS: The SD rats(n=36) were randomly divided into control group, IgAN model group, IgAN with prednisone treatment group and IgAN with pidotimod treatment group, with 9 rats in each group. The IgAN model was induced by consecutive oral administration of bovine gamma globulin(BGG) for 8 weeks followed by injection of BGG through tail vein for 3 d. After the IgAN model was established, the drug was continuously used for 4 weeks. At the end of the treatment, the urine protein, serum creatinine and blood urea nitrogen were examined by an automated analyzer. IgA deposition in the renal tissues was observed by immunofluorescence staining. The mRNA expression levels of renal fibrosis markers transforming growth factor-β1(TGF-β1) and fibronectin 1 in the renal tissues were detected by RT-qPCR. The mRNA and protein levels of pro-inflammatory cytokines interleukin-1β(IL-1β) and IL-6 in the renal tissues were determined by RT-qPCR and Western blot, respectively. RESULTS: No significant difference of the body weight was observed in different groups. Compared with control group, the content of urine protein, serum creatinine and blood urea nitrogen were significantly increased(P<0.01), whereas those were reversed by pidotimod treatment. The results of immunofluorescence staining showed that pidotimod inhibited IgA deposition in the IgAN rats. Pitomod treatment inhibited the mRNA expression levels of renal fibrosis markers TGF-β1 and fibronectin 1, and the mRNA and protein levels of pro-inflammatory cytokines IL-1β and IL-6 in the renal tissues of IgAN rats. CONCLUSION: Pidotimod alleviates IgAN progression in rats by inhibition of inflammatory response.