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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 observe the effects of sulodexide on peritoneal structure and function in chronic peritoneal dialysis rats. Methods Thirty-six male Sprague-Dawley rats were randomly divided into 4 groups: blank control group (n = 6), model group (n = 10), low dose [10 mg / (kg · d) 10), high-dose [20 mg / (kg.d)] sulodexide (n = 10). The peritoneal balance test (PET) was performed 1 h after dialysis for 8 weeks. The contents of urea nitrogen (Durea), total protein (Dtp) in dialysate, initial peritoneal dialysate glucose concentration D0, D0, D1, Purea and Ptp were calculated and D / Purea (indicating peritoneal NO removal efficiency), D / Ptp (peritoneal dialysis fluid Total protein loss), D1 / D0 (indicating the ability of ultrafiltration). The changes of peritoneal structure were observed by HE and Masson staining. The peritoneal thickness, number of peritoneal blood vessels and inflammatory cells were calculated semi-quantitatively. The number of white blood cells in peritoneal dialysis fluid was calculated. The levels of MCP-1 and TNF-α The expression of TGF-β1 in parietal peritoneum was detected by immunohistochemistry. Results Compared with the control group, the peritoneal mesothelial cells were decreased, the mesangial matrix was thickened, the inflammatory cells were increased, the vascular hyperplasia was significantly increased (P <0.05), the peritoneal ultrafiltration volume and the D1 / D0 decreased, (P <0.05), the number of white blood cells, the level of MCP-1 and TNF-α in peritoneal dialysis fluid increased (P <0.05) and the expression of TGF-β1 in visceral peritoneum increased The changes of the structure were alleviated, the infiltration of peritoneal inflammatory cells and the decrease of vascular hyperplasia, the peritoneal function were improved, the levels of MCP-1 and TNF-α in the peritoneal dialysis fluid were decreased (P <0.05), and the expression of TGF-β1 in the visceral peritoneum was decreased. Conclusion Schuluutide may inhibit peritoneal fibrosis and improve peritoneal function by inhibiting chronic peritoneal inflammation.