前列地尔注入高糖腹膜透析液对实验大鼠腹膜纤维化的影响  

Effects of Alprostadil on experimental peritoneal fibrosis in rats

作　　者：张燕敏[1] 陈伟栋[1] 万胜[1] 陈丹[1] 陈芳[1] 丁艳琼[1] 张妙[1] 田洪丹[1] 熊飞[1] 

机构地区：[1]武汉市第一医院肾内科

出　　处：《临床肾脏病杂志》2015年第8期497-501,共5页Journal Of Clinical Nephrology

基　　金：武汉市科技局科技攻关项目(NO.201260523191-2)

摘　　要：目的探讨前列地尔加入高糖腹膜透析液对大鼠腹膜纤维化的影响和可能的机制。方法采用高糖腹膜透析液＋脂多糖腹腔注射制备大鼠腹膜纤维化模型。将大鼠随机分为对照组、模型组、前列地尔低剂量组、前列地尔中剂量组和前列地尔高剂量组。3个前列地尔治疗组是在造模同时每日腹腔内注射含不同剂量前列地尔的腹透液。6周后各组大鼠行2h腹膜平衡试验，检测0h腹膜透析液葡萄糖浓度（D0），2h透出液葡萄糖浓度（D2），透析液肌酐浓度（D），血浆肌酐浓度（Pcr），计算D／Pcr和D2／D0，测量超滤量。留取血液及腹膜透析液标本，用ELISA法分别测定血液及腹膜透析液中转化生长因子β（transforming growth factor β，TGF-β），单核细胞趋化蛋白-1（monocyte chemotactic protein-1，MCP-1）、白介素6（interleukin-6，IL-6）含量。留取壁层腹膜组织行病理切片做HE及Masson染色，新生血管计数采用免疫组化法检测CD31的表达率；免疫组化法测定腹膜组织TLR4、TGF-β的表达率。结果前列地尔治疗组与模型组相比，超滤量及D2／D0均明显增加，而D／Pcr则明显降低，腹透液血液中TGF-β的含量以及血液中IL-16的含量降低、腹膜组织中Toll样受体4（Toll like receptor 4，TLR4）、TGF-β的表达降低，腹膜新生血管密度减少；前列地尔中剂量组在超滤量、D／Pcr、新生血管密度、腹透液及血液TGF-β水平、腹膜组织中TLR4表达均与优于低剂量组，且与高剂量组无显著性差异；前列地尔高剂量组仅在腹膜组织中TGF-β的表达以及血液中IL-6的水平下调方面优于其他治疗组，且与对照组无显著性差异。结论前列地尔可以有效的防治腹膜纤维化的进程，中剂量前列地尔注入高糖腹透液对大鼠腹膜纤维化的干预最佳。Objective To investigate the effects and possible action mechanism of Alprostadil in the treatment of experimental peritoneal fibrosis in rats. Methods The rat peritoneal fibrosis model was induced by high glucose dialysate and lipopotysaccharide （LPS）. The rats were randomly divided into five groups： control group, model group, low-dose Alprostadil-treated group, middle-dose Alprostadil-treated group and high-dose Alprostadiktreated group. The Alprostadil-treated groups received daily intraperitoneal injection of different doses of Alprostadil. Six weeks later all rats were anaesthetized. The peritoneal membrane function was investigated by peritoneal equilibration test （PET）. The abdominal membrane was stained with HE and Masson method. The levels of TGF-β and TLR4 in peritoneum were detected by immunohistochemical method. Results The number of vascularity in model group was greater than that in Alprostadil-treated groups. The concentrations of TGFβ and TLR4 in blood and dialysate were also decreased obviously in Alprostadil-treated groups. The levels of TGFβ and TLR4 in peritoneumin in Alprostadil-treated groups were significantly lower than those in model group. Conclusions Alprostadil are beneficial to the prevention and treatment of peritoneal fibrosis in experimental model rats.

关 键 词：腹膜纤维化 前列地尔 转化生长因子-Β TOLL样受体4 

分 类 号：R692.5[医药卫生—泌尿科学]