不同浓度葡萄糖透析液及LPS对腹膜透析大鼠腹膜组织VEGF及血管增生的影响及其意义

Effects and significance of different glucose concentrations and LPS on the expression of VEGF and vascular proliferation in the peritoneal membrane of dialysis rat

目的探讨不同浓度葡萄糖透析液及LPS对大鼠腹膜组织血管内皮生长因子(VEGF)表达及血管增生的影响,揭示其影响腹膜转运功能的机制。方法SD大鼠分成A、B、C、D、E五组,A组为正常对照组,其余各组分别每天腹腔注射1.50%、2.50%、4.25%和4.25%腹膜透析液,E组同时注射脂多糖。分别用RT-PCR、免疫荧光检测VEGF的表达及新生血管的数目,同时检测各组超滤量。结果VEGF的表达随着透析液葡萄糖浓度增加而增加,E组表达最强,RT-PCR结果显示:E组VEGF mRNA表达较A升高约11倍[(65±11.35)vs(5.33±2.3);P<0.001];同时CD31免疫组化也显示腹膜新生血管的数目也逐渐增多,E组较A组升高约8倍[(12.2±2.65)vs(1.33±1);P<0.001]。且随着透析液浓度增加其超滤量逐渐减少。结论腹膜组织可表达VEGF。高糖透析液和LPS均能促进腹膜VEGF表达、促进腹膜新生血管的增生,从而增加腹膜转运的有效滤过面积,减少超滤量。这可能是葡萄糖透析液及LPS影响腹膜转运功能的重要机制之一。

[Objective] To investigate the effects of different concentrations glucose and LPS on the expression of VEGF （vascular endothelial growth factor） and vascular proliferation in the peitoneal membrane of dialysis rat. and to reveal the mechanism of peritoneal transport. [Methods] SD rats were divided into five group. Group A was normal control group, and other group were daily received respectively intraperitoneal injection of 1.5%, 2.5%, 4.25%, 4.25% glucose peritoneal dialysis fluid, and group E was also received intraperitoneal injection of LPS besides 4.25% glucose peritoneal dialysis fluid. RT-PCR, immunofluorescence and immunohistochemistry technology were employed to detect the expression of VEGF and number of vascular vessels, and the amount of uhrafihration in five groups was also measured. [Results] The expression of VEGF increased gradually with the increasing of glucose concentration, and Group E was most significant of all five group. RT-PCR reveal that there was a 11-fold up-regu-lation of VEGF mRNA expression in group E compared with that of group A[（65±11.35） vs （5.33±2.3）; P 〈0.001]; And it accompanied with new Vascular vessels increased, Immunohistochemistry of CD31 show that the number of peritoneal new Vascular vessels in group E was increased 8-fold than that of group A[（12.2±2.65） vs （1.33±1）; P 〈 0.001]. At the same time, the amount of net ultrafiltration was gradually decreased with the increasing of glucose concentration. [Conclusions] Peritoneal membrane tissue can express VEGF. Glucose peritoneal dialysis fluid and LPS can promote the expression of VEGF, and advanced the new Vascular proliferation, thus increase the effective peritoneal surface area （EPSA） of peritoneal membrane and lead to the reduction of net ultrafiltration. This may be the important mechanism of Glucose peritoneal dialysis fluid and LPS influenceing peritoneal function.