不同腹膜纤维化大鼠模型之比较

目的:采用几种不同方法构建腹膜透析腹膜纤维化大鼠模型，为腹膜透析腹膜纤维化的防治提供可研究的动物模型。方法:34只SD雄性大鼠(200～250g)，随机分为5组，分别是空白对照组(n=7，未予任何处理)、生理盐水组(n=7，每日腹腔内直接注射0.9%生理盐水20ml)、高糖组(n=7，每日腹腔内直接注射4.25%含糖透析液即PDF 20ml)、高糖＋脂多糖(LPS)组(n=6，每日腹腔内直接注射4.25% PDF 20ml，并在第8,10,12天加入LPS 75μg)、高糖＋红霉素组(n=7,每日腹腔内直接注射4.25% PDF 20ml，并在第7,14,21,28天加入乳糖酸红霉素6.25万U)，观察5周。分别于第0，7，14，21，28，35天清晨，空腹状态时测量大鼠体重。5周后行2h腹膜平衡试验(PET)，处死大鼠，准确测量超滤量，检测腹膜功能；观察腹膜厚度、血管数及其他组织学改变；用免疫组织化学法测定腹膜组织及肠管腹腔侧组织纤维连接蛋白(FN)表达率。结果:高糖组、高糖+脂多糖组和高糖+红霉素组皆可见腹膜间皮细胞脱落，间皮下基质及肠外纵肌层明显增厚，可见大量成纤维样细胞及单核、巨噬细胞浸润，且有纤维素样物质沉积等现象，尤以高糖+红霉素组明显；与空白对照组及生理盐水组分别比较，高糖、高糖+脂多糖及高糖+红霉素组大鼠超滤量及2h透出液葡萄糖浓度/０h透析液葡萄糖浓度(D2/D0)比值均有明显减少(P<0.05)，而透析液尿素浓度/血浆尿素浓度(D/Purea)比值、大鼠腹膜组织及肠管腹腔侧组织FN表达率均有明显增加(P<0.05)；与高糖组比较，高糖+红霉素组D/Purea比值、大鼠腹膜组织及肠管腹腔侧组织FN表达率均有明显增加(P<0.05)；与高糖组比较，高糖+脂多糖组D/Purea比值及肠管腹腔侧组织FN表达率皆明显增加(P<0.05)；而在大鼠每周体重变化、透出液中白细胞计数、超滤量、D2/D0比值等方面，高糖、高糖+红霉素和高糖+脂多糖组之间的差异无统计学意义(P>0.05)。结论:采用高糖、高糖+脂多糖和高糖+红霉素刺激均能充分复制腹膜透析腹膜纤维化特征，而以高糖+红霉素效果为最佳。

Comparision of several different peritoneal fibrosis rat models

Objective To compare different types of peritoneal fibrosis models in rats. Methods Thirty-four SD rats were divided into 5 groups: control group (Group 1), normal saline group (Group 2), high glucose group (4.25% peritoneal dialysate, 4.25% PDF, Group 3), high glucose lipopolysaceharides (LPS) group (4.25% PDF LPS, Group 4), high glucose erythromycin group (4.25% PDF lactobionate erythromycin, Group 5). A 2-hour peritoneal equilibration test (PET) was performed after 5 weeks. Then animals were humanely killed. Dialysate-to-plasma urea ratio (D/Purea), glucose reabsorption (D 2 /D 0 ), net ultrafiltration (UF) volume were determined. The level of fibronectin in peritoneal tissues was measured by immunohistochemical method. Peritoneal membrane histology was evaluated by light microscopy. Results The D 2 /D 0 ratio and net ultrafiltration volume in Groups 3, 4, and 5 were significantly lower than those in Groups 1 and 2 ( P <0.05). The D/Purea ratio in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 ( P <0.05). The level of fibronectin in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 ( P <0.05). Conclusion Different types of peritoneal fibrosis models in rats has been established. The best model is high glucose erythromycin.