橙皮苷对IgA肾病大鼠肾脏组织中PAI-1蛋白表达的影响

摘要

目的 探讨橙皮苷对IgA肾病大鼠纤溶酶原激活物抑制物(PAI-1)表达的影响.方法 60只雄性SD大鼠,随机分为正常组,模型组和橙皮苷治疗组,每组20只,模型建立成功后给予相应药物治疗,于治疗4、8周后处死大鼠各半,检测血肌酐(Scr)、尿素氮(BUN),肾脏病理学,同时半定量PCR和Western Blot测定PAI-1蛋白和mRNA表达水平.结果 造模期间模型组、治疗组与正常组相比,大鼠第6周末开始出现镜下血尿(P<0.05),橙皮苷治疗后,有一定下降(P<0.05);与正常组相比,模型组血清24 h UP、Scr、BUN、IL-2和PAF明显升高(P<0.05),治疗组治疗4周后明显下降(P<0.05),治疗8周后进一步降低;PLT和PT在治疗前后没有明显变化;与正常组相比,模型组APTT明显降低(P<0.05),治疗4周后明显升高(P<0.05),治疗8周后进一步升高;光镜下正常组大鼠肾小球形态正常,模型组肾小球系膜细胞和系膜基质中重度增生,橙皮苷治疗后肾小球系膜细胞和系膜基质增生得到明显缓解;与正常组相比,模型组PAI-1蛋白和mRNA表达明显降低,橙皮苷治疗4周后明显升高(P<0.05),治疗8周后基本和治疗4周后一致.结论 橙皮苷可明显减少血尿、减轻病理改变,改善肾功能,其机制可能是橙皮苷通过增加PAI-1的产生而发挥作用的.%Objective To investigate the effects of hesperidin to fibrinolytic enzyme original activators inhibitor (PAI-1) protein expression in IgA nephropathy of rats. Methods 60 male SD rats were randomly divided into the normal group, model group and hesperidin treatment group, each group were 20. After successful establishment of the model, the corresponding drugs were given. Half of the rats were sacrificed at 4 and 8 weeks after treatment, and to detected the serum creatinine (Scr), urea nitrogen (BUN), kidney pathology examination, using RT-PCR and Western Blot to detected the PAI-1 protein and mRNA expression. Results During the period of building models, model group and hesperidin treatment group compared with normal group rats began to appear microscopic haematuria from 6 week (P<0.05), after hesperidin treatment, which have a certain degree decreased (P<0.05); Compared with normal group, 24 hUP, Scr, BUN, IL-2 and PAF levels were increased significantly in model group (P<0.05), after 4 weeks treatment significantly decreased (P<0.05), after 8 weeks treatment further reduce; PLT and PT did not change significantly before and after the treatment; Compared with normal group, APTT was significantly decrease in model group (P<0.05), after 4 weeks treatment it was significantly increased (P<0.05), after 8 weeks treatment it was further increase; Under light microscope, glomerular morphology of normal rats was normal, and mesangial cells and mesangial matrix of the model group had moderate and severe hyperplasia, the proliferation of glomerular mesangial cells and mesangial matrix was relieved after treatment with hesperidin; Compared with the normal group, the expression of PAI-1 protein and mRNA in the model group was significantly reduced, and the level was significantly increased after 4 weeks of treatment (P<0.05), After 8 weeks of treatment, the effect was consistent with the effect after treatment for 4 weeks. Conclusion: Hesperidin can obviously reduce the hematuria and alleviate pathological changes, improve renal function, the mechanism may be related with increase production of PAI-1.