醛固酮在腹膜透析大鼠腹膜纤维化中的作用

目的:研究醛固酮在腹膜透析大鼠腹膜纤维化中的作用,以及醛固酮受体拮抗剂是否能够减轻腹膜纤维化。方法:通过腹腔注射脂多糖(第1、3、5、7天,0.6 mg/kg)+透析液(每天腹腔注射4.25%含糖透析液100 m L/kg)建立伴有腹膜纤维化的腹膜透析大鼠模型。同时给予醛固酮受体拮抗剂(螺内酯,100 mg·kg-1·d-1)灌胃。4周后取大鼠腹膜行病理和免疫组化检测,同时采用real-time PCR和Western blot法检测醛固酮合成酶(CYP11B2)、11β-羟基类固醇脱氢酶2型(11β-HSD2)、盐皮质激素受体(MCR)和炎症因子的表达情况。结果:成功建立伴有腹膜纤维化的腹膜透析大鼠模型,发现腹膜间皮细胞受损,形态改变,胶原纤维沉积,腹膜增厚,腹膜和腹透液中巨噬细胞浸润增多。与正常大鼠相比,腹膜上MCR、11β-HSD2和CYP11B2表达增高,醛固酮含量增多。同时腹膜上NF-κB/MCP-1表达增加。而给予螺内酯治疗后腹膜纤维化减轻,NF-κB/MCP-1表达减少。结论:局部产生的醛固酮可能通过NF-κB/MCP-1途径参与腹膜纤维化过程。醛固酮受体拮抗剂螺内酯能够减轻腹膜透析大鼠的腹膜纤维化程度。

Effect of aldosterone on rat peritoneal fibrosis induced by peritoneal dia-lysis

AIM: To investigate the pathologic role of aldosterone and protective effect of aldosterone receptor antagonist on peritoneal fibrosis in peritoneal dialysis rats. METHODS: A peritoneal fibrosis rat model was established by intraperitoneal injection of lipopolysaccharide(at 1 d, 3 d, 5 d and 7 d, 0.6 mg/kg) and dialysate(daily intraperitoneal injection of 4.25% dialysate, 100 mL/kg). At the same time, spironolactone(an aldosterone receptor antagonist, 100 mg·kg^-1·d^-1) was given to the model rats. After 4 weeks, the expression of aldosterone synthase CYP11B2, 11β-hydroxysteroid dehydrogenase type 2(11β-HSD2), mineralocorticoid receptor(MCR), and inflammatory factors were detected by immunohistochemistry, real-time PCR and Western blotting. RESULTS: The rat model of peritoneal fibrosis was successfully established. At the same time, the injury of mesothelial cells, deposition of collagen fibers and thickness of peritoneal were increased. Moreover, the infiltration of macrophages in the peritoneum/dialysate was increased. The level of aldosterone and the expression of MCR, 11β-HSD2 and CYP11B2 in fibrotic peritoneum were obviously up-regulated as compared with normal rats. The expression of NF-κB/MCP-1 was also increased. However, treatment with spironolactone alleviated peritoneal fibrosis and reduced the expression of NF-κB/MCP-1. CONCLUSION: Local aldosterone is involved in the process of peritoneal fibrosis via NF-κB/MCP-1 pathway. Spironolactone alleviates peritoneal fibrosis of peritoneal dialysis.