舒洛地特对腹膜透析大鼠腹膜结构和功能的作用  

Effect of sulodexide on peritoneal morphology and function of peritoneal dialysis rats

作　　者：韦永光[1] 林沁[1,2] 戢晴[1] 郑丰[1,2] 

机构地区：[1]福建医科大学福州总医院临床医学院肾内科,福州350025 [2]南京军区福州总医院肾内科,福州350025

出　　处：《第二军医大学学报》2011年第3期276-281,共6页Academic Journal of Second Military Medical University

基　　金：福建省科技厅重点资助项目(2008Y0085)~~

摘　　要：目的观察舒洛地特对慢性腹膜透析大鼠腹膜结构和功能的作用。方法 36只SD雄性大鼠随机分为4组:空白对照组(n=6)、模型组(n=10)、低剂量[10 mg/(kg.d)]舒洛地特组(n=10)、高剂量[20 mg/(kg.d)]舒洛地特组(n=10)。透析8周后行1 h腹膜平衡试验(PET);使用全自动生化分析仪测定1 h腹膜平衡试验透出液中尿素氮(Durea)、透出液中总蛋白(Dtp)、初始腹透液葡萄糖浓度(D0)、透出液葡萄糖浓度(D1)、血浆尿素氮(Purea)及血浆总蛋白(Ptp),并计算D/Purea(说明腹膜对尿素氮清除效率)、D/Ptp(评估腹膜透析液中总蛋白丢失情况)、D1/D0(表示腹透超滤的能力)。取壁层腹膜行H-E及Masson染色观察腹膜结构变化,半定量计算腹膜厚度、腹膜单位面积血管及炎症细胞数;计算腹透液中白细胞数;ELISA法检测腹透液MCP-1及TNF-α水平;免疫组化检测壁层腹膜TGF-β1表达情况。结果与对照组相比,长期腹透大鼠腹膜间皮细胞减少,间皮下基质增厚,炎症细胞增多,血管增生明显(P<0.05),腹膜超滤量和D1/D0减少,D/Purea及D/Ptp增加(P<0.05),腹透液中白细胞数、MCP-1及TNF-α水平上调(P<0.05),脏层腹膜TGF-β1表达上调;给予舒洛地特干预后腹膜结构改变减轻,腹膜组织炎症细胞浸润和血管增生减少,腹膜功能改善,腹透液MCP-1及TNF-α水平下调(P<0.05),脏层腹膜TGF-β1表达下调。结论舒洛地特可能通过抑制腹膜慢性炎症来达到抑制腹膜纤维化及改善腹膜功能的作用。Objective To investigate the effect of sulodexide on the peritoneal morphology and function of long-term peritoneal dialysis rats.Methods Adult male Sprague-Dawley rats were randomly divided into the following four groups： control group（n=6）,model group（n=10）,low-dose sulodexide group（n=10） and high-dose sulodexide group（n=10）.A 1 hour peritoneal equilibration test was performed after an eight-week peritoneal dialysis in each group.The dialysate samples were subjected to examination by hemocytometer for determination of 1 h dialysate urea（Durea）,dialysate protein（Dtp）,initial dialysate glucose（D0） and 1 h dialysate glucose（D1）,plasma urea nitrogen（Purea）and total plasma protein（Ptp）;and the D/Purea（parameter for clearance rate of urea nitrogen）,D/Ptp（parameter for total protein loss in dialysate）,and D1/D0（parameter for peritoneal ultrafiltration）were calculated.The parietal peritoneum tissues of rats were harvested and stained by Hematoxylin-eosin and Masson trichrome for observation of the peritoneal structure.The vessels and leukocytes in peritoneum tissue were counted（n/mm2） using stained sections.Leukocytes in dialysate samples were evaluated using hemocytometer.The levels of inflammatory cytokine（MCP-1,TNFα） in dialysate samples were measured by enzyme-linked immunosorbent assay（ELISA） and the expression of TGF-β1 in parietal peritoneum was detected by immunohistochemistry assay.Results Compared with the control group,rats in the model group had decreased peritoneal mesothelial cells,thickened sub-mesothelial matrix,increased inflammatory cells,and angiogenesis（P〈0.05）.The ultrafilitration volume（UF） and glucose reabsorption（D1/D0） were significantly lower and the dialysate-to-plasma urea ratio（D/Purea） and dialysate-to-plasma total protein ratio（D/Ptp） were significantly higher in model group than those in the control group（P〈0.05）.Counts of leukocytes and levels of MCP-1 and TNFα in dialysate samples were sign

关 键 词：腹膜透析 腹膜纤维化 糖胺聚糖 舒洛地特 

分 类 号：R459.51[医药卫生—治疗学]