川芎嗪注射液对腹膜透析大鼠腹膜功能及相关蛋白的影响

The Experimental Research of Peritoneal Structure and Function Affected by Ligustrazine in the Course of Peritoneal Dialysis Rats

目的:研究川芎嗪注射液对腹膜透析大鼠腹膜组织结构和功能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:将56只SD大鼠分为7组,即正常对照组、低糖腹透液(peritoneal dialysis solution,PDS)组(1.5%PDS)、高糖腹透液组(4.25%PDS)、低糖腹透液+低浓度川芎嗪组(1.5%PDS+2‰川芎嗪注射液)、低糖腹透液+高浓度川芎嗪组(1.5%PDS+4‰川芎嗪注射液)、高糖腹透液+低浓度川芎嗪组(4.25%PDS+2‰川芎嗪注射液)、高糖腹透液+高浓度川芎嗪组(4.25%PDS+4‰川芎嗪注射液)。大鼠腹腔注射腹膜透析液8周后,检测腹透超滤量、腹膜对毒素的清除率以及腹透液漏出的蛋白含量;在光镜和电镜下观察腹膜结构变化;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,低糖PDS组和高糖PDS组大鼠腹膜结构和功能发生改变,腹膜的病理改变明显,超滤量减少(P<0.05),对肌酐清除能力下降(P<0.01),AQP-1蛋白表达增加(P<0.05),其中高糖PDS组ZO-1蛋白表达减少(P<0.05);低糖PDS+川芎嗪注射液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尿素氮清除率提高。与1.5%PDS组比较,1.5%PDS+2‰川芎嗪注射液组及1.5%PDS+4‰川芎嗪注射液组腹膜AQP-1蛋白表达量减少(P<0.05)。4.25%PDS+2‰川芎嗪注射液组较高糖腹透液组ZO-1表达量显著增加(P<0.05)。结论:川芎嗪注射液可能通过下调AQP-1、促进ZO-1表达,增加腹膜超滤量,提高腹膜对毒素的清除率,拮抗腹透液对腹膜组织结构和功能的损伤。

Objective：To study the effects of Ligustrazine Injection on peritoneal structure and function of peritoneal dialysis rats . To study the relationgship between Ligustrazine Injection and aquaporin-1 （ AQP-1 ） and zonula occluden-1 （ ZO-1 ） rela-tionship. Methods：56 SD rats were divided into 7 groups：normal group, 1. 5%PDS group, 4. 25%PDS group,1. 5%PDS＋2‰Li-gustrazine Injection group, 1. 5%PDS＋4‰Ligustrazine Injection group, 4. 25%PDS＋2‰Ligustrazine Injection group, 4. 25%PDS＋4‰ Ligustrazine Injection group. Rats were intraperitoneally injected with PDS after 8 weeks. The clearance rate of urea nitrogen, creatinine, glucose, between Dialysate and plasma, total protein in the PDS, and the volume dose of ultrafiltration were examined. Peritoneal membrane histology was evaluated by light microscopy and transmission electron microscopy. Immunohistochemistry was used to investigate the expression of ZO-1and AQP-1 in mesothelial cell. Results：Using of dialysate in different concentration not only caused the destruction of structure but also induced the change in function of peritoneum, including decrease of ultrafiltration and clearance efficiency, P〈0. 05. With the change of peritoneal structure, PDS had increased the expression of AQP-1 and reduced the expression of ZO-1. Danshen or chuanxiong into dialysate decreased the damage of PDS to peritoneum and improved the clearance rate of substance such as urea nitrogen, creatinine and glucose so on, P〈0. 05. And it also made educing of AQP-1 and the rising of ZO-1, P〈0. 05. Conclusion：Ligustrazine injection could reduce AQP-1, promote the expression of ZO-1, increase the peri-toneal ultrafiltration volume, improve the rate of peritoneal clearance of toxins, damage antagonist of peritoneal dialysis solution on the structure and function of peritoneal tissue.