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来氟米特对慢性肾小球肾炎大鼠炎症介质和免疫功能的影响

Effect of Leflunomideon Inflammatory Factors and Immune Function in Rats with Chronic Glomerulonephritis

  • 摘要: 目的 探讨来氟米特对慢性肾小球肾炎模型大鼠炎症介质以及免疫功能的影响。方法 采用注射阳离子化小牛血清白蛋白(C-BSA)法建立大鼠慢性肾小球肾炎模型,建模成功后随机分为模型组和观察组(每组15只),另设15只大鼠作为对照组,以生理盐水替代C-BSA进行相同方式注射处理。建模2周后,观察组给予来氟米特混悬液灌胃治疗, 5 mg/(kg·d),对照组和模型组给予等体积生理盐水灌胃。连续灌胃4周后处死各组大鼠,记录血肌酐、血尿素氮、血总胆固醇、血白蛋白及24 h尿蛋白排泄量,采用RT-PCR和ELISA法测定各组大鼠外周血肿瘤坏死因子-α (TNF-α) 和白细胞介素-6 (IL-6) mRNA和蛋白水平;采用流式细胞术检测各组大鼠外周血T淋巴细胞亚群比例。结果 与对照组相比,模型组和观察组治疗前大鼠血肌酐、血尿素氮、血总胆固醇、血清白蛋白及24 h尿蛋白水平均升高( P<0.05);与模型组相比,治疗后观察组大鼠各项生化指标均下降( P<0.05);与对照组相比,模型组和观察组治疗前大鼠外周血TNF-α、IL-6 mRNA和蛋白水平均升高( P<0.05);与模型组相比,治疗后观察组大鼠TNF-α、IL-6 mRNA和蛋白水平均下降( P<0.05);与对照组相比,模型组和观察组大鼠治疗前外周血T淋巴细胞亚群比例明显失调( P<0.05);与模型相比,观察组大鼠治疗后外周血T淋巴细胞亚群比例趋于稳定,接近对照组水平( P>0.05)。结论 来氟米特能够显著降低慢性肾小球肾炎模型大鼠24 h尿蛋白、血肌酐等生化指标,抑制炎症反应,其机制可能与其对免疫功能的调节作用相关。

     

    Abstract: Objective To investigate the effect of leflunomide on the inflammatory factors and immune function of rats with chronic glomerulonephritis. Methods Thirty rats of chronic glomerular nephritis model were established by injecting cationic bovine serum albumin (C-BSA). Rats with successfully modeled were randomly divided into model group and observation group. Another 15 rats injected with physiological saline in the same way were chosen as the control group. Modeling after 2 weeks, rats in the observation group were given leflunomide meters suspension by gavage treatment with 5 mg/(kg·d). Rats in the control group and model group were given equal volume of saline. Rats were killed after continuous intragastric for 4 weeks. The levels of serum creatinine, blood urea nitrogen, serum total cholesterol, serum albumin and 24 h urine protein were recorded. mRNA and protein levels of peripheral blood tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were detected by RT-PCR and ELISA method. Peripheral blood T lymphocyte subsets were evaluated by flow cytometry (FCM). Results Compared with the control group, the levels of serum creatinine, blood urea nitrogen, serum total cholesterol, serum albumin and 24 h urine protein in model group and observation group were significantly increased ( P<0.05); Compared with the model group, these biochemical indexes in observation group decreased significantly ( P<0.05). Comparison with the control group, mRNA and protein levels of peripheral blood TNF-α and IL-6 in model group and observation group rats were significantly increased ( P<0.05). Compared with the model group, mRNA and protein levels of TNF-α and IL-6 were significantly decreased ( P<0.05). Compared with the control group, peripheral blood T lymphocyte subsets in the model group and observation group were imbalance, the difference was significant ( P<0.05). Compared with the model rats, T lymphocyte subsets in the observation group after treatment tended to be stable ( P>0.05). Conclusion Leflunomide can significantly reduce the levels of biochemical indexes and inhibit the inflammatory reaction. The mechanism may be related to the regulation of immune function.

     

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