摘要
目的:观察孟根乌苏(水银)-18味丸对大鼠肾汞蓄积及肾早期损伤指标的影响。方法:将Wistar雄性大鼠,根据体质量随机分为正常对照组,孟根乌苏(水银)-18味丸低剂量组[0.29 g·(kg·d)^(-1)]、中剂量组[1.47 g·(kg·d)^(-1)]、高剂量组[(2.9 g·(kg·d)^(-1)],孟根乌苏(水银)炮制品低剂量组[0.033 g·(kg·d)^(-1)],硫化汞组[17.39 mg·(kg·d)^(-1)]、氯化汞组[4.06 mg·(kg·d)-1],氯化亚汞组[7.06 mg·(kg·d)^(-1)],共8组,每组10只。各组大鼠适应1周后,灌胃给药15 d后分别计算肾脏指数,检测大鼠血清尿素、肌酐,肾组织形态学变化,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)测肾汞蓄积量;并于实验第7天和第15天,收集24 h尿液,用尿液分析仪检测尿蛋白和pH值,酶联免疫吸附法(Elisa)检测尿液β-N-乙酰氨基葡萄糖苷酶(n-acetyl-β-glucosaminidase,NAG)、尿视黄醇结合蛋白(retinol binding protein,RBP)、β2-微球蛋白(β2-microglobulin,β2-MG)、肾损伤因子-1(kidney injury factor,KIM-1)含量。结果:大鼠连续给药15 d后,与正常对照组和孟根乌苏炮制品低剂量组比较,氯化汞组、氯化亚汞组大鼠肾脏指数显著升高(P<0.01);各组大鼠血清肌酐和尿素含量无显著差异(P>0.05)。肾脏病理检查结果表明,孟根乌苏-18味丸低剂量组,即临床常用剂量组大鼠肾脏出现了一定的病理损伤,表现为肾小球轻度肥大,肾小管上皮中度肿胀变性;孟根乌苏-18味丸中剂量组和高剂量组肾脏也出现了一定损伤,硫化汞、氯化汞、氯化亚汞组大鼠肾病理变化更显著。与正常对照组和孟根乌苏炮制品低剂量组比较,氯化汞组和氯化亚汞组大鼠肾汞蓄积量显著升高(P<0.01);给药7d和15 d后,孟根乌苏-18味丸各剂量组尿蛋白和尿液NAG、β2-MG、RBP和KIM-1含量无显著差异(P>0.05);给药7 d后,氯化汞组尿蛋白有升高趋势,尿液β2-MG含量显著升高(P<0.01),给药15 d时,尿蛋白有升高趋势,尿液β2-MG、KIM-1含量显著升高(P<0.01,P<0.05);给药7 d和15 d后,氯化亚汞组尿蛋白有升高趋势,尿液RBP、β2-MG、KIM-1含量显著升高(均为P<0.05)。结论:大鼠连续给药15 d后,孟根乌苏-18味丸肾汞蓄积量和尿液NAG、β2-MG、RBP、KIM-1含量无显著变化。
Objective：To observe the effects of Mengen Wusu （mercury）-18 flavor pill on the accumulation of mercury in the kid- ney and the index of early renal injury. Methods ： Male Wistar rats were randomly divided into 8 groups ： normal control group, low dose of mercury-18 group [ 0.29 g· （kg · d） -1、, middle dose of of mercury-I 8 group [ 1. 47 kg · d -1 ）, high dose of mercury- 18 group [ （2.9 g ·（kg ·d） -1）] and low dose of processed mercury-18 group （0.033 g ·（kg ·d） -1] ,mercury sulfide group [17.39 mg· （kg·d）-1],mercuric chloride group [4.06 mg· （kg· d） -lj and mercuric chloride group [7.06 mg · （kg·d） -l ] ,with 10 rats in each group. After 1 week,the rats were given intragastric administration for 15 days. The renal index was calculated. The serum urea, ereatinine and renal morphological changes were examined and the accumulation of mercury in the kid- ney was measured with （ICP-OES） and inductively coupled plasma mass spectrometry （ICP-MS）. On the 7th and 15th day of the experiment,24 hours urine was collected and analyzed with a urine analyzer （NAG） and retinol binding protein （NAG） was measured by enzyme linked immunosorbent assay （ ELISA）. The urine protein and pH were also measured. The retinol binding protein （RBP） , β2-microglobulin （β2-MG） and Kidney injury factor （ KIM-1 ） were detected by immunohistochemistry. Results： Compared with the normal control group and the low dose group, the renal index of rats in the mercury chloride group and the mer- cury chloride group increased significantly （ P 〈 0.01 ） after 15 days of continuous administration. There was no significant differ- ence in the serum creatinine and urea between the two groups （ P 〉 0. 05 ）. Kidney pathological examination showed that the patho- logical changes of renal tissue were observed in the low dose group of Mengen Wusu-18 Pill, with mildly hypertrophy of glomerulus and moderately swollen degeneration of renal tubular epithelium. There was also some damage in the middle dose group and the high dose group, and the renal pathological changes were more obvious in the group of mercury sulphide, mercuric chloride and mercury mercuric chloride. Compared with the normal control group and the low dose group, the mercury accumulation in the mer- cury chloride group and mercury chloride group significantly increased （P 〈 0.01 ）. After 7 and 15 days, There were no significant differences in urinary protein and urine NAG, β2-MG, RBP and KIM-1 between the two groups （P 〉 0.05 ）. After 7 days of admin- istration, the Urine β2-MG level significantly increased （P 〈 0.01 ）. Urine β2-MG and KIM-1 levels significantly increased at 15 days after administration （ P 〈 0.01 ,P 〈 0.01 ） （ P 〈 0.05 ）. Urine levels of RBP, β2-MG and KIM-1 significantly increased after 7 and 15 days of administration. Conclusion ：There were no significant changes in the accumulation of mercury and the contents of NAG, β2-MG, RBP and KIM-1 in the urine of rats after 15 days of continuous administration of Mangen Wusu-18-flavor pill.
出处
《中医学报》
CAS
2017年第1期71-77,共7页
Acta Chinese Medicine
基金
国家"十二五"科技支撑计划项目(2012BAI27B05)
