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目的:研究交感神经抑制剂莫索尼定及贝那普利对肾病模型大鼠肾组织细胞外基质调节因子基质金属蛋白酶-9(MMP-9)、基质金属蛋白组织抑制因子-1(TI MP-1)的影响。方法:大鼠右肾摘除加尾静脉注射多柔比星建立肾病模型后,随机分为模型组、莫索尼定组、贝那普利组、假手术对照组。给药12周后测定生化指标及肾组织相关指标;免疫组化检测肾组织MMP-9、TI MP-1蛋白表达;原位杂交测MMP-9 mRNA、TI MP-1 mRNA表达。结果:与假手术对照组比较,模型组大鼠肾组织内MMP-9、TIMP-1蛋白及mRNA表达均明显上调;2个药物治疗组与模型组比较,MMP-9蛋白及mRNA表达进一步上调,生化指标、肾组织相关指标及TI MP-1表达均被显著抑制。结论:莫索尼定和贝那普利均具有肾保护作用,部分机制可能是通过抑制交感神经活性、调节细胞外基质降解而发挥。
OBJECTIVE: To investigate the effect of sympathomimetic inhibitors moxonidine and benazepril on renal extracellular matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TI MP- 1) influence. Methods: After the right kidney was removed and the tail vein was injected with doxorubicin to establish nephropathy model, the rats were randomly divided into model group, moxonidine group, benazepril group and sham operation control group. After 12 weeks of administration, the biochemical indexes and the indexes related to the renal tissues were determined. The expressions of MMP-9 and TI-MP-1 in renal tissues were detected by immunohistochemistry. The expressions of MMP-9 mRNA and TI MP-1 mRNA were detected by in situ hybridization. Results: Compared with the sham-operated control group, the expressions of MMP-9 and TIMP-1 protein and mRNA in renal tissue of model group were significantly increased. Compared with the model group, MMP-9 protein and mRNA expression were up-regulated , Biochemical indicators, renal tissue related indicators and TI MP-1 expression were significantly inhibited. Conclusion: Both moxonidine and benazepril have renal protective effects. Some mechanisms may play a role in inhibiting sympathetic activity and regulating the degradation of extracellular matrix.