扶肾颗粒通过调节AGEs的生成抑制腹膜透析大鼠腹膜纤维化作用机制研究

Study on mechanism of Fushen Granules inhibiting peritoneal fibrosiss of peritoneal dialysis rats by regulating the generation of AGEs

目的:探讨扶肾颗粒通过调节腹膜组织晚期糖基化终末产物(AGEs)的表达,改善腹膜纤维化的作用机制。方法:健康雄性SD大鼠83只,适应性喂养1周后随机分为5组:正常对照组(A组),5/6肾切除+1.5%PDS组(B组),5/6肾切除+1.5%PDS组+扶肾颗粒组(C组),5/6肾切除+4.25%PDS组(D组),5/6肾切除+4.25%PDS+扶肾颗粒组(E组);4周后免疫组化法检测各组大鼠腹膜组织AGEs的表达情况,酶联免疫法检测各组大鼠晚期糖基化终末产物受体(RAGE)及表皮生长因子受体(EGFR)的表达变化。结果:与A组比较,模型组(B组、D组)AGEs表达水平均显著性升高(P<0.05),扶肾颗粒干预组(C组、E组)AGEs表达水平较模型组(B组、D组)降低(P<0.05);模型组(B组、D组)RAGE及EGFR表达均高于A组(P<0.05),扶肾颗粒干预组(C组、E组)RAGE及EGFR表达均低于模型组(B组、D组)(P<0.05)。结论:扶肾颗粒可能通过减少腹膜AGEs的生成,抑制AGEs-RAGE信号通路,从而下调RAGE以及EGFR的表达水平,进而改善腹膜透析大鼠腹膜纤维化。

Objective： To explore the mechanism of Fushen Granules inproving peritoneal fibrosis by regulating the expression of peritoneal tissue advanced glycation end-products（AGEs）. Methods： Eighty-three healthy male SD rats were randomly divided into five groups after one week of adaptive feeding： normal control group（group A）, renal failure with 5/6 resection＋1.5%PDS group（group B）, renal failure with 5/6 resection＋1.5%PDS＋Fushen Granules group（group C）, renal failure 5/6 resection＋4.25%PDS group（group D）, renal failure 5/6 resection＋4.25%PDS＋Fushen Granules group（group E）. After 4 weeks, the expression of AGEs in peritoneal tissues of rats in each group was detected by immunohistochemistry. The expression of changes of receptor for advanced glycation end-products（RAGE） and epidermal growth factor receptor（EGFR） in each group were detected by enzyme-linked immunoassay. Results： Compared with normal control group, the expression level of AGEs in model group（group B and group E） were both significantly increased（P〈0.05）. The expression level of AGEs in Fushen Granules group（group C and group D） were lower than the model group（group B and group D）（P〈0.05）. The expression levels of RAFE and EGFR in the model group（group B and group D） were higher than the normal control group（P〈0.05）. The expression levels of RAGE and EGFR of Fushen Granules group（group C and group E） were lower than the model group（group B and group D）（P〈0.05）. Conclusion： Fushen Granules can improve peritoneal fibrosis of peritoneal dialysis rats, maybe by reducing the generation of the peritoneal AGEs, inhibiting the signaling pathway of AGEs-RAGE, then down-regulating the expression levels of RAGE and EGFR.