大黄总蒽醌对大鼠肾脏水通道蛋白2和水通道蛋白4表达的影响  

Effects of total anthraquinone in rheum on aquaporin 2, 4 expression in rat kidney

作　　者：鲍军强[1] 李锋[1] 张文生[1] 王汉民[2] 刘青[1] 韩骅[3] 梁亮[3] 杜永平[1] 

机构地区：[1]第四军医大学西京医院中医科,西安710032 [2]第四军医大学西京医院肾脏内科,西安710032 [3]第四军医大学遗传与发育教研室

出　　处：《中华肾脏病杂志》2008年第8期581-585,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30572385）

摘　　要：目的研究大黄总蒽醌对大鼠肾脏水通道蛋白（AQP）2、AQP4表达的影响及探讨大黄利尿机制。方法32只SD大鼠随机分为正常对照组，大黄总蒽醌低、中、高剂量组，每组8只，分别给予不同剂量大黄总蒽醌灌胃，每天1次，共灌5d。第4天测定大鼠24h尿量，尿液Na^＋水平及尿渗透浓度。5d后处死大鼠，腹主动脉取血，进行血液生化指标检测；并留取肾脏，用免疫组化、Western印迹和RT—PCR法检测肾脏AQP2、AQP4蛋白及mRNA表达变化。结果与正常对照组比较，大黄总蒽醌中、高剂量组大鼠24h尿量显著增加[（16．21±1．96）ml、（18．16±1．80）ml比（13．85±1．25）ml，P均〈0．05]，低剂量组大鼠尿量变化不明显；中、高剂量组大鼠肾脏AQP2蛋白及mRNA表达均显著下降（P均〈0．01），高剂量组大鼠肾脏AQP4蛋白及mRNA表达显著下降（P〈0．01）；中剂量组大鼠AQP4蛋白表达下降（P〈0．01），但mRNA表达无显著降低；低剂量组大鼠AQP2、AQP4蛋白及mRNA表达无显著变化。结论大黄总蒽醌能降低大鼠肾脏AQP2、AQP4蛋白及mRNA表达水平，这可能是大黄产生利尿的机制之一。Objective To investigate the effects of total anthraquinone in rheum on aquaporin 2 and aquaporin 4 expression in rat kidney and explore its diuresis mechanism. Methods Thirty-two SD rats were randomly divided into control group, low dose group, medium dose group and high dose group. Total anthraquinone in rheum was administered to rats at different doses. Urinary volume of 24 h, Na^＋ concentration and osmolality were detected. Rats were sacrificed 5 days later. Blood samples were taken from the abdominal aorta to detect blood biochemical indicators. Kidneys of rats were removed to detect AQP2, AQP4 expression through immunohistochemistry, Western blot, and RT-PCR. Results Compared with control group, there were significantly increased 24 h urine output of rats in medium and high dose group[（16.21± 1.96）, （18.16±1.8） ml vs（ 13.85±1.25）ml, P〈0.05]. 24 h urine output in low-dose group did not change significantly. AQP2 protein and mRNA expression were significantly decreased in rats＇ kidneys of medium and high dose group （P〈0.01）, The AQP4 protein and mRNA expression was significantly down-regulated in high dose group （P〈0.01）. In medium does group, the AQP4 protein expression was down-regulated （P〈0.01）, without significant decrease in the mRNA expression. Protein and mRNA expression of AQP2 and AQP4 did not significantly change in low dose group. Conclusion Total anthraquinone in rheum can reduce the expression level of AQP2 and AQP4 in rat kidney, which is probably one mechanism of diuresis caused by rheum.

关 键 词：大黄 蒽醌苷 肾脏 利尿 水通道蛋白2 水通道蛋白4 

分 类 号：R285.5[医药卫生—中药学]