中国血液净化

›› 2007, Vol. 6 ›› Issue (12): 656-659.

• 基础研究 • 上一篇    下一篇

醛固酮受体拮抗剂联合ACEI抗腹膜纤维化机制的研究

赵向阳1 郝丽荣2 李春玲1 李鹏飞3 崔志伟4
  

  1. 150001 哈尔滨，1哈尔滨医科大学第一临床医学院血液透析中心（赵向阳为在读研究生） 163311 大庆，2哈尔滨医科大学第五临床医学院肾内科 163300 大庆，3大庆油田总医院病理科
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2007-12-12 发布日期:2007-12-12

  • Received:1900-01-01 Revised:1900-01-01 Online:2007-12-12 Published:2007-12-12

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摘要： 目的 ①药物干预腹膜纤维化的机制研究； ②观察单核细胞趋化蛋白-1(MCP-1)、C-JUN/AP-1在大鼠腹膜间皮细胞的表达及其在药物干预后的变化，探讨腹膜透析后腹膜纤维化的机制及解决办法。 方法 50只Wistar大鼠随机分5组。除A 组余腹腔内每日注入20毫升4.25%百特透析液，试验第1、3、5、7天腹腔注射脂多糖(LPS)0.6ml/(kg•h)， B组 腹膜纤维化模型组；C组西拉普利10mg/(kg•d)灌胃；D组安体舒通100mg/(kg•d)灌胃。E组联合给药组。30天后收集大鼠腹膜做病理(HE染色 ,Masson染色)，免疫组化查腹膜间皮细胞MCP-1、C-JUN/AP-1的表达，并腹膜透析液计数腹水中细胞总数和巨噬细胞数及测定转化生长因子-β(TGF-β)的浓度。结果 给药组(C、D、E组)的腹膜病理改变比模型组(B组)轻，转化生长因子-β的浓度下降具有统计学意义 。各组腹膜间皮细胞均有MCP-1的表达，毛细血管和小静脉内皮细胞都可见其表达,联合给药组腹膜纤维化程度最轻，腹水巨噬细胞计数少, MCP-1、C-JUN/AP-1的表达少。结论 联合应用醛固酮(ALDO)受体拮抗剂及ACEI能有效的防治腹膜纤维化。机制可能为抑制腹膜间皮细胞C-JUN/AP-1 表达，在转录的水平上降低TGF-β活性，并抑制MCP-1表达，抑制腹膜炎性反应，减轻纤维化。

关键词: 血管紧张素转换酶抑制剂, 醛固酮受体拮抗剂, 腹膜纤维化, MCP-1 C-JUN/AP-1

Abstract:

Objective To investigate the effect and possible mechanism of aldosterone receptor blocker and Angiotensin-converting Enzyme Inhibitor on peritoneal fibrosis. Methods 50 male Wistar rats were divided into three groups at random,Group A (n = 10) control group, B、C、D、E (n = 10) received daily intraperitoneal injection of 20 mL 4.25% Beter dialysate .on day 1、3、5、7, The rats was given intraperitoneal injection of LPS 0.6ml/(kg•h)Group B (n=10)modle groupC、D、E (n=10) medicine group, GroupC: angiotensin-converting enzyme inhibitor 10mg/(kg•d)was given orally to rats by gastric gavage in the morning once a day.GroupD:Aldosterone eceptor blocker. 100mg/(kg•d) was given orally to rats by gastric gavage in once a day.Thirty days later all rats were sacrificed. the parietal peritoneum was stained with HE and Masson. Total cell counts and macrophage counts in dialysate. To measure TGF-f abdominal cavity liquid of peritoneal dialysis rats. With ELISA method，and to measure the express of abdominal membrane MCP-1 and C-JUN with immunological histochemical method. Results TGF- obviously increased in Both B and C、D、E groups as compared to A group (P＜0.01) , group C、D is more serious than group E (P＜0.01), so do histopathology of peritoneum. Conclusions Aldosterone eceptor blocker and Angiotensin-converting Enzyme Inhibitor functions as an inhibitors of TGF-xpression in dialysate and suppressed MCP-1 expression in abdominal membrane possibly via down-regulation of c-Jun/activator protein-1. It demonstrate used Aldosterone eceptor blocker and Angiotensin-converting Enzyme at the same time more efficency than use one on inhibit Peritoneal fibrosis.

Key words: Aldosterone receptor blocker, Peritoneal fibrosis, Monocyte chemoattractant protein-1, C-Jun/activator protein-1

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