丹参注射液减轻腹透液致大鼠腹膜结构和功能损伤

目的：研究丹参注射液对腹透液（peritoneal dialysis solution,PDS）致大鼠腹膜组织结构和功能损伤的影响及与水通道蛋白1（aquaporin-1,AQP-1）和紧密连接相关蛋白1（zonula occluden-1,ZO-1）的关系。方法：56只SD大鼠分为正常对照组、1.5%PDS组、4.25%PDS组、1.5%PDS＋1%丹参组、4.25%PDS＋1%丹参组、1.5%PDS＋2%丹参组和4.25%PDS＋2%丹参组。腹膜透析液大鼠腹腔注射8周后,检测腹膜透析超滤量、腹膜对物质的清除率和腹透液漏出蛋白含量;光镜和电镜下观察腹膜结构变化;免疫印迹法检测腹膜AQP-1蛋白表达,免疫组织化学法检测腹膜间皮细胞ZO-1和AQP-1蛋白表达。结果：与正常对照组比较,1.5%PDS组和4.25%PDS组大鼠腹膜结构和功能发生改变,包括腹膜病理的改变明显,超滤量减少（P〈0.05）,对肌酐和葡萄糖清除能力下降（P〈0.01）,AQP-1蛋白表达增加（P〈0.05）;1.5%PDS＋2%丹参组和4.25%PDS＋2%丹参组大鼠腹膜结构和功能较单纯腹透液组改善,表现为病理改变缓解,腹膜超滤量以及肌酐和葡萄糖清除率提高。与1.5%PDS组比较,1.5%PDS＋2%丹参组腹膜AQP-1蛋白表达量减少（P〈0.05）。结论：丹参注射液可能通过下调AQP-1蛋白表达拮抗腹透液对腹膜组织结构和功能的损伤。

Salvia Miltiorrhiza injection relieves peritoneal dialysis solution-induced injuries of peritoneal structure and function in rats

OBJECTIVE: To investigate the effect of Salvia Miltiorrhiza injection (SMI) on peritoneal dialysis solution (PDS) induced injuries of peritoneal structure and function in a rat model, and to observe the relationship between the failure of peritoneal dialysis and expressions of aquaporin-1 (AQP-1) and zonula occluden-1 (ZO-1) in peritoneal tissues. METHODS: Fifty-six SD rats were randomly divided into normal control group, 1.5% PDS group, 4.25% PDS group, 1.5%PDS+1% SMI group, 1.5%PDS+2% SMI group, 4.25% PDS+1% SMI group and 4.25% PDS+2% SMI group. Two-hour peritoneal dialysis test was performed in rats in different groups by intraperitoneal injection for 8-week. Then rats were killed on the 8th week, and the bloods and peritoneal tissues were gathered. The rate of ultrafiltration, clearance rates of urea nitrogen, creatinine and glucose of peritoneum and content of total protein in PDS were detected. Peritoneal membrane histology was evaluated by light microscopy and transmission electron microscopy. Expressions of ZO-1 and AQP-1 proteins in peritoneal tissues were detected by immunohistochemical method, and AQP-1 protein expression was also detected by Western blotting technique. RESULTS: Compared with normal control group, using of 1.5% PDS and 4.25% PDS caused the changes of structure and function in peritoneum, such as pathological change of peritoneum, decreasing of the rate of ultrafiltration (P<0.05), clearance rates of creatinine and glucose (P<0.01) and the expression of ZO-1 protein (P<0.05), and increasing of the expression of AQP-1 protein (P<0.05). Compared with the simple PDS groups, the pathological damage of peritoneum was lessened and the rate of ultrafiltration and clearance rates of creatinine and glucose were increased in the 1.5% PDS+2% SMI group and 1.5% PDS+2% SMI group. Expression of AQP-1 protein was decreased by 1.5% PDS+2% SMI as compared with 1.5% PDS (P<0.05).[JP] CONCLUSION: SMI can relieve the injuries of function and structure of peritoneum by down-regulating the expression of AQP-1 protein.