氟伐他汀对腹膜透析大鼠腹膜组织保护作用的初步研究

发布时间：2018-05-02 03:11

本文选题：氟伐他汀 + 腹膜透析　；参考：《南京医科大学》2014年硕士论文

【摘要】：目的：探讨氟伐他汀(fluvastatin, Flu)对腹膜透析大鼠腹膜组织的保护作用。方法：通过每日规律腹腔注射2.5%或4.25%浓度的葡萄糖腹透液建立腹膜透析大鼠模型。将42只SD雄性大鼠(体质量180-200g)随机分为7个组：(1)正常对照组；(2)生理盐水组：每日往大鼠腹腔注射100ml/kg生理盐水；(3)单纯Flu组：每日灌入10mg/kg氟伐他汀；(4)2.5%腹透液组：每日往大鼠腹腔注射100ml/kg2.5%葡萄糖腹透液；(5)4.25%腹透液组：每日往大鼠腹腔注射100ml/kg4.25%葡萄糖腹透液；(6)Flu干预的2.5%腹透液组：每日往大鼠腹腔注射100ml/kg2.5%葡萄糖腹透液并同时灌入10mg/kg氟伐他汀；(7)Flu干预的4.25%腹透液组：每日往大鼠腹腔注射100ml/kg4.25%葡萄糖腹透液并同时灌入10mg/kg氟伐他汀。6周后留取大鼠壁层腹膜组织,光镜观察各组大鼠壁层腹膜形态学的变化,同时采用RT-PCR法及免疫组化法(immunohistochemical, IHC)分别测定各组大鼠壁层腹膜分泌的转化生长因子-β1(transforming growth factor,TGF-β1)及纤维连接蛋白(fibronectin, FN)的mRNA及蛋白表达量。结果：光镜下HE染色和Masson染色均显示4.25%腹透液组与2.5%腹透液组大鼠腹膜较正常对照组明显增厚；Flu干预的不同浓度腹透液组的壁层腹膜厚度薄于相应未干预的葡萄糖腹透液组,但仍厚于正常对照组；生理盐水组和氟伐他汀组大鼠腹膜的厚度较正常对照组未见明显改变。RT-PCR及IHC显示2.5%腹透液组与4.25%腹透液组的TGF-β1和FN的mRNA及蛋白的表达量均明显高于正常对照组(均P0.05), Flu干预的2.5%腹透液组的TGF-β1和FN的mRNA及蛋白的表达量较无Flu干预的2.5%葡萄糖腹透液组有显著减少(均P0.05),Flu干预的4.25%腹透液组的TGF-β1和FN的mRNA及蛋白的表达量较无Flu干预的4.25%腹透液组亦有显著减少(均P0.05),生理盐水组和氟伐他汀组大鼠腹膜TGF-β1和FN的mRNA及蛋白表达量较正常组无明显统计学意义(均P0.05)。结论：氟伐他汀能改善高糖腹透液环境下大鼠腹膜的厚度,同时降低高糖腹透液诱导的大鼠腹膜TGF-β1和FN mRNA及蛋白的表达,对腹膜有保护作用。
[Abstract]:Aim: to investigate the protective effect of fluvastatin fluvastatin (Fluvastatin) on peritoneal tissue in peritoneal dialysis rats. Methods: peritoneal dialysis rat model was established by intraperitoneal injection of 2.5% or 4.25% glucose peritoneal dialysis solution. Forty-two Sprague-Dawley male rats (body mass 180-200g) were randomly divided into 7 groups: control group (n = 7) normal control group (n = 2) normal saline group: intraperitoneal injection of 100ml/kg saline to rats daily (n = 3) Flu group: daily administration of 10mg/kg fluvastatin and 42.5% peritoneal dialysate group: Rats were injected intraperitoneally with 100ml / kg 2.5% glucose peritoneal dialysate 54.25% peritoneal dialysate group: rats were injected 100 ml / kg 4.25% glucose peritoneal dialysate group with 2.5% Flu daily intraperitoneal injection of 100ml / kg 2.5% glucose peritoneal dialysate and simultaneously 10mg/kg fluvastation. The rats were given intraperitoneal injection of 100 ml / kg 4.25% glucose peritoneal dialysate daily with 10mg/kg fluvastatin at the same time for 6 weeks, and the peritoneal tissue of the rat wall layer was taken after the injection of fluvastatin at the same time for 6 weeks, in the group of 4.25% peritoneal dialysate, the rats were given intraperitoneal injection of 100 ml / kg 4.25% glucose per day. The morphologic changes of parietal peritoneum were observed under light microscope. The expression of transforming growth factor-尾 1(transforming growth factor- TGF- 尾 1 and fibronectin (FNs) in parietal peritoneum of rats in each group were measured by RT-PCR method and immunohistochemical method respectively. Results: under light microscope, HE staining and Masson staining showed that the peritoneal thickness of peritoneal layer of rats in 4.25% peritoneal dialysate group and 2.5% peritoneal dialysis group was significantly thicker than that in the control group treated with different concentrations of Flu, and the thickness of the parietal peritoneum in the peritoneal dialysate group with different concentrations was thinner than that in the corresponding glucose peritoneal dialysate group. But it was still thicker than the normal control group. The thickness of peritoneal membrane in saline group and fluvastatin group was not significantly changed compared with normal control group. RT-PCR and IHC showed that the expression of TGF- 尾 1 and FN mRNA and protein in 2.5% peritoneal dialysis group and 4.25% peritoneal dialysis group were significantly higher than those in normal control group (P < 0.05). The expression of mRNA and protein of TGF- 尾 1 and FN in 2.5% peritoneal dialysis group treated with Flu was significantly lower than that in 2.5% glucose peritoneal dialysis group without Flu intervention. The mRNA and protein expression of TGF- 尾 1 and FN in peritoneal membrane of rats in saline group and fluvastatin group were significantly lower than those in control group (all P 0.05). Conclusion: fluvastatin can improve the peritoneal thickness and decrease the expression of TGF- 尾 1 and FN mRNA and protein induced by high glucose peritoneal dialysis in rats.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.5

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