高糖和抗生素对大鼠腹膜间皮细胞表达PAI和TGF-βmRNA的影响

HYPEROSMOTIC GLUCOSE AND ANTIBIOTICS INDUCE PRODUCTION OF PLASMINOGEN ACTIVATOR INHIBITOR AND EXPRESSION OF TGFβ mRNA BY RAT PERITONEAL MESOTHELIAL CELLS

为探讨腹膜硬化的发生机制，采用腹膜间皮细胞培养、纤维蛋白平板方法和Ｎｏｒｔｈｅｒｎ杂交技术观察了不同浓度葡萄糖和抗生素庆大霉素与头孢唑啉钠对大鼠腹膜间皮细胞纤溶酶原激活物抑制物（ＰＡＩ）产生和转化生长因子－β（ＴＧＦ－β）ｍＲＮＡ表达的影响。结果表明腹膜间皮细胞可表达ＰＡＩ－１ｍＲＮＡ和产生活性ＰＡＩ；培养１２小时，１１．２ｍｍｏｌ／Ｌ的高渗葡萄糖、庆大霉素和头孢唑啉钠可增强腹膜间皮细胞ＰＡＩ－１ｍＲＮＡ的表达和增加活性ＰＡＩ的分泌；培养至２４小时，１１．２ｍｍｏｌ／Ｌ的高渗葡萄糖继续诱导腹膜间皮细胞产生活性ＰＡＩ增加，庆大霉素既可以继续引起ＰＡＩ－１ｍＲＮＡ表达增加，而且还可以使腹膜间皮细胞活性ＰＡＩ产生增加。同时在培养２４小时，１１．２ｍｍｏｌ／Ｌ的高渗葡萄糖和庆大霉素与头孢唑啉钠均可引起腹膜间皮细胞ＴＧＦ－βｍＲＮＡ表达增加。结果提示：１１．２ｍｍｏｌ／Ｌ的高渗葡萄糖和庆大霉素与头孢唑啉钠可以导致间皮细胞表达ＰＡＩ和ＴＧＦ－β上调，在腹膜硬化发生机制中起着重要作用。

To investigate the mechanism of fibrosis in peritoneal dialysis, we observed the effects of the hyperosmotic glucose and antibiotics such as gentamicin and cefazolin on rat peritoneal mesothelial cells with cell culture, fibrin plate lyzing and Northern blotting analysis method. The peritoneal mesothelial cells may express PAI 1 mRNA. The expressions of PAI 1 mRNA in peritoneal mesothelial cells and acti vities of PAI in the supernatants were enhanced by 11.2 mmol/L glucose, gentamicin and cefazolin at 12hr. By 24hr, the activity of PAI 1 also increased in the supernatants with 11.2 mmol/L glucose. The expressions of PAI 1 mRNA and production of PAI activities by the peritoneal mesothelial cells were increased by gentamicin, and the TGF β mRNA increased in the peritoneal mesothelial cells was induced by 11.2 mmol/L glucose, gentamicin and cefazolin. The results suggested that 11.2 mmol/L glucose, gentamicin and cefazolin may increase the expressions or productions of PAI and TGF β in peritoneal mesothelial cells. So by perosmotic glucose, cefazolin and gentamicin promote the peritoneal fibrosis in patients with CAPD.