马兜铃酸I和马兜铃内酰胺I对大鼠肾小管损伤机制及其对肾脏水通道蛋白1表达的影响  

Tubular Injury Mechanism of Aristolochic Acid I and Aristololactam I in Rats and Their Effect on Renal Aquaporin 1 Expression

作　　者：张良[1,2] 李霁[2] 江振洲[2] 卞勇[1] 袁冬平[1] 龙军[1] 张陆勇[2] 

机构地区：[1]南京中医药大学药理教研室,南京210046 [2]中国药科大学新药筛选中心,南京210009

出　　处：《中药新药与临床药理》2011年第4期359-364,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金(30701106)

摘　　要：目的研究马兜铃酸I(AA-I)和马兜铃内酰胺I(AL-I)在亚急性毒性条件下对大鼠肾小管损伤的毒性机制及其对肾脏水通道蛋白1(AQP1)表达的影响。方法 AA-I及AL-I以高、中、低剂量(9.0,4.5,2.25 mg/kg)连续腹腔注射给药7 d,在给药第5天后,收集24 h尿液,对各组总尿量进行比较,并用ELISA方法检测尿液中β2-微球蛋白(β2-MG)含量。给药7 d后,取全血检测血生化,并用HE法染色观察肾脏病理组织学变化;用ELISA和免疫组织化学方法分析AA-I及AL-I在高、中、低剂量时肾脏组织AQP1的表达变化。结果 AA-I及AL-I在给药第5天即出现β2-MG排泄量增加,血生化中血浆离子浓度出现异常。AA-I及AL-I在9.0、4.5、2.25 mg/kg的剂量下均能明显抑制AQP1的表达,且存在一定的剂量依赖关系。结论 AA-I及AL-I均能导致肾脏毒性,且AL-I的肾毒性作用强于AA-I。AA-I及AL-I在肾小管损伤早期均可抑制AQP1表达,这与其早期导致大鼠尿量增加的利尿作用有关。Objective To investigate the role of aquaporin I（AQP1 ） in toxicity of aristolochic acid I（AA-I） and aris- tololactam I（AL- I） on renal tubules. Methods Rats were intraperitoneally injected with AA-I and AL- I at the dose of 2.25, 4.5 and 9.0 mg/kg once daily for 7 days. On day 5, total urine volume in all of the groups was counted, and the content of β2-microglobulin in the urine was detected with enzyme-linked immunosorbent assay（ELISA）. On day 7, blood biochemical parameters were analyzed, renal pathological changes were examined, and AQP1 expression was detected by ELISA and immunohistochemical assay. Results From day 5 of the medication, β2-microglobulin was in- creased dose-dependently, plasma K＋, Na＋ and Cl- became abnormal, and the expression of AQP1 was inhibited in dose-dependent manner. Conclusion It is indicated that both AA-I and AL-I could induce the injury of kidney, and the nephrotoxicity of AL-I is stronger than that of AA-I. The nephrotoxicity mechanism of AA-I and AL-I may be related with the inhibition of expression of AQP1, which results in the early increase of urine volume in rats.

关 键 词：马兜铃酸I 马兜铃内酰胺I Β2-微球蛋白 肾小管损伤 水通道蛋白1 

分 类 号：R285.5[医药卫生—中药学]