高糖透析液对大鼠腹膜结缔组织生长因子表达的作用

目的探讨腹膜透析液对大鼠腹膜结缔组织生长因子（CTGF）的表达及细胞外基质（ECM）合成的影响。方法将中南大学湘雅二医院动物实验中心提供的SD大鼠随机分为4组：正常对照组（Con）、生理盐水组（NS）、低糖透析液组（LG）、高糖透析液组（HG）。4周后,评价腹膜的功能。VG染色镜下测量腹膜胶原组织厚度。免疫组织化学方法检测CTGF、TGF-β1及纤连蛋白（FN）蛋白质的表达。采用RT-PCR检测大鼠腹膜组织中CTGF和TGF-β1mRNA的表达。结果LG、HG组与Con、NS组相比较,超滤量均显著下降（P〈0.05）;HG组与LG组比较,其超滤量明显减少（P〈0.05）。D/Pcr的比较：HG组比Con、NS组升高（P〈0.05）;D/DO的比较：HG组比Con、NS组明显下降（P〈0.05）,LG组比Con组低（P〈0.05）。HG组腹膜胶原厚度比与其余各组均增厚（P〈0.05）;LG组比Con组增厚（P〈0.05）;HG组CTGF、TGF-β1、FN蛋白表达水平显著高于其他各组（P〈0.05）;LG组显著高于Con、NS组（P〈0.05）。在Con及NS组中,TGF-β1、CTGFmRNA呈低水平表达,TGF-β1、CTGFmRNA在HG组中表达最高（P〈0.05）。结论腹膜透析液尤其是高糖腹膜透析液,能明显诱导大鼠腹膜CTGF的表达增强,并促使腹膜纤维化发生。

High glucose peritoneal dialysate on expression of connective tissue growth factor in rat peritoneum

Objective To investigate the effect of peritoneal dialysis fluids on connective tissue growth factor （CTGF） expression and extracellular matrix synthesis in the peritoneum of peritoneal dialysis rats. Methods Sprague-Dawley rats were randomly divided into 4 groups based on the dialysate used： control group （Con）, 0.9% saline solution （NS） group, 1.5% Dianeal （LG） group and 4.25% Dianeal （HG） group. Peritoneal function was estimated and peritoneal collagen thickness was measured 4 weeks after the treatment. Transforming growth factor beta 1 （TGF- β1）, CTGF, fibronectin （FN） were detected by immunohistochemistry. RT-PCR was used to evaluate the expression of TGF- β1 and CTGF mRNAs. Results The ultrafiltratlon volume was lower in LG and HG groups than in Con and NS groups （P 〈0.05）, and was lower in HG group than in LG group （P 〈0.05）. D/Pcr was higher in HG group than in Con and NS groups （P 〈0.05）. D/D0 glucose was lower in HG group than in Con and NS groups, and was lower in LG group than in Con group （P 〈0,05）. The collagen of peritoneal membrane was thicker in HG group than in other groups （P 〈0.05）, and was thicker in LG group than in Con group （P 〈0.05）. TGF- β 1 and CTGF mRNA and their proteins were higher in LG and HG groups than in Con and NS groups （P 〈0.05）, and were significantly higher in HG group than in LG group （P 〈0.05）. FN protein was significantly increased in HG group, as compared with that in other groups （P 〈0.05）, and was higher in LG group than in Con and NS groups （P 〈0.05）. Conclusion Peritoneal dialysis fluids, especially those containing higher concentrations of glucose, up-regulates the expression of CTGF mRNA and its protein, and contributes to the peritoneal fibrosis.