摘要
目的:观察孟根乌苏(水银)-18味丸对大鼠肾脏毒性及探讨毒性机制。方法:Wistar雄性大鼠,根据体质量随机分成10组,每组20只,即正常对照组,孟根乌苏炮制品低、中、高剂量组(0.033、0.167、0.330g·kg-1·d-1),孟根乌苏-18味丸简化方组(0.26g·kg-1·d-1),孟根乌苏-18味丸低、中、高剂量组(0.29、1.47、2.90g·kg-1·d-1),硫化汞组(17.39mg·kg-1·d-1)、氯化汞组(4.06mg·kg-1·d-1)。大鼠分别于连续给药30d和停药15d后,计算肾脏指数,检测血清尿素(UREA)、肌酐(CREA),用电感耦合等离子体发射光谱仪(ICP-OES)和电感耦合等离子体质谱仪(ICP-MS)法测肾汞蓄积量,酶联免疫吸附法(ELISA)检测肾脏组织还原型谷胱甘肽(GSH)、一氧化氮(NO)和总超氧化物歧化酶(T-SOD)含量,分光光度法检测丙二醛(MDA)含量。结果:连续给药30d,与正常对照组比较,孟根乌苏炮制品和孟根乌苏-18味丸高剂量组,氯化汞组大鼠CREA、UREA含量显著升高(P<0.01,P<0.05);氯化汞组大鼠肾汞蓄积量显著升高(P<0.01);孟根乌苏炮制品和孟根乌苏-18味丸中剂量和高剂量组,硫化汞、氯化汞组大鼠肾脏GSH显著降低(P<0.01,P<0.05);孟根乌苏炮制品和孟根乌苏-18味丸高剂量组,氯化汞组大鼠肾脏NO显著升高(P<0.05)。停药15d,孟根乌苏炮制品和孟根乌苏-18味丸高剂量组,氯化汞组大鼠肾功能恢复正常;孟根乌苏-18味丸各剂量组大鼠肾脏病理变化有所恢复;氯化汞组大鼠肾汞蓄积量仍显著升高(P<0.01);硫化汞、氯化汞组大鼠肾脏GSH仍显著降低(P<0.01),氯化汞组大鼠肾脏NO仍显著升高(P<0.05)。结论:大鼠连续给药孟根乌苏(水银)-18味丸30d造成肾组织损伤,其机制与氧化损伤有关,停药后肾组织损伤可逐步恢复。
Objective： To observe Meng-Gen-Wu-Su-18-Composition Pill-induced nephrotoxicity and its underlying mechanism. Methods： Two hundred male Wistar rats were randomly divided into 10 groups according to the weight（20 rats per group）： the control group, low, middle and high dose groups（0.033, 0.167, 0.330g·kg-1·d-1） of processing Meng-Gen-Wu-Su, simplified prescription of Meng-Gen-Wu-Su-18-Composition Pill group（0.26g·kg-1·d-1）, low, middle and high dose groups（0.29, 1.47, 2.90g·kg-1·d-1） of Meng-Gen-Wu-Su-18-Composition Pill, mercuric sulfide group（17.39mg·kg-1·d-1） and mercuric chloride group（4.06mg·kg-1·d-1）. The renal index was calculated respectively at 30 days after continuous gavages and 15 days after drug withdrawal and the contents of urea（UREA） and creatinine（CREA） in serum were detected. Mercury accumulation in kidneywas determined by inductively coupled plasma optical emission spectroscopy（ICP-OES） and inductively coupled plasma source mass spectrometer（ICP-MS）. Enzyme-linked immunosorbent assay（ELISA） was used to detect the contents of renal reduced glutathione（GSH）, nitrogen monoxide（NO） and total superoxide dismutase（T-SOD）. The contents of Malondialdehyde（MDA） were detected by spectrophotometric method. Results： After 30 days continuous gavages, compared with the control group, the contents of UREA and CREA in serum in high dose group of Meng-Gen-Wu-Su-18-Composition Pill, processing Meng-GenWu-Su group and mercuric chloride group increased significantly（P〈0.01, P〈0.05）; The renal mercury accumulation in mercuric chloride group increased significantly（P〈0.01）; The contents of renal GSH in middle and high dose groups of processing MengGen-Wu-Su and Meng-Gen-Wu-Su-18-Composition Pill group, along with mercuric sulfide group and mercuric chloride group decreased significantly（P〈0.01, P〈0.05）. The content of renal NO in high dose group of Meng-Gen-Wu-Su, Meng-Gen-Wu-Su-18-Composition Pill group and mercuric chloride group increased significantly（P〈0.05）. After 15 days of drug withdrawal, renal function in high dose group of processing Meng-Gen-Wu-Su, Meng-Gen-Wu-Su-18-Composition Pill group and mercuric chloride group backed to normal; renal pathological changes in each group of Meng-Gen-Wu-Su-18-Composition Pill recovered to in some extent; renal mercury accumulation in mercuric chloride group still increased significantly（P〈0.01）; renal GSH contents in mercuric sulfide and mercuric chloride groups still decreased significantly（P〈0.01）; renal NO content in mercuric chloride group increased significantly（P〈0.05）. Conclusion： Thirty days of continuous gavages of Meng-Gen-Wu-Su-18-Composition Pill could cause renal tissue damages, the mechanisms of which may be oxidative damage, and such renal tissue damages could recovery gradually after drugs withdrawal.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2016年第12期5260-5265,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家"十二五"科技支撑计划项目(No.2012BAI27B05)~~
