文章摘要
佟海英 范盎然 于雪 白亮凤 张月 乌吉斯古冷 李婧 呼日乐巴根.蒙药孟根乌苏-18 味丸、孟根乌苏炮制品的肝肾毒性作用研究[J].,2016,16(1):25-33
蒙药孟根乌苏-18 味丸、孟根乌苏炮制品的肝肾毒性作用研究
Study on Hepatoxicity and Nephrotoxicity of Mongolian Meng-Gen-Wu-Su(Mercury)-18-Composition Pill, Mongolian Meng-Gen-Wu-Su (Mercury)Processed Products and Mercuric Sulfide, Mercuric Chloride, MercurousChloride
  
DOI:
中文关键词: 孟根乌苏(水银)-18 味丸  孟根乌苏(水银)炮制品  汞化合物  肝肾毒性
英文关键词: Meng-Gen-Wu-Su-18-CompositionPill  Meng-Gen-Wu-SuProcessedProducts  Mercuric compounds  hepatorenal toxicity
基金项目:国家" 十二五" 科技支撑计划项目(2012BAI27B05)
作者单位
佟海英 范盎然 于雪 白亮凤 张月 乌吉斯古冷 李婧 呼日乐巴根 北京中医药大学民族医药学研究所北京中医药大学基础医学院内蒙古医科大学蒙医药学院 
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中文摘要:
      目的:对比研究孟根乌苏(水银)-18 味丸、孟根乌苏(水银)炮制品与硫化汞、氯化汞、氯化亚汞的肝肾毒性作用。方法:将 Wistar 雄性大鼠,根据体重随机分为正常对照组、孟根乌苏-18 味丸低、高剂量组(0.29,2.9 g·kg-1·d-1)、孟根乌苏-18 味丸简化方 组(0.26 g·kg-1·d-1)、孟根乌苏炮制品低、高剂量组(0.033,0.33 g·kg-1·d-1)、硫化汞组(17.39 mg·kg-1·d-1)、氯化汞组(4.06 mg·kg-1· d-1)、氯化亚汞组(35.3 mg·kg-1·d-1),共9 组,每组6 只。各组大鼠适应7 天后,灌胃给药7 天后分别检测肝肾功能,肝肾组织形态 学变化,并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,原位末端标记 (TUNEL)法测肾细胞凋亡,免疫组化法测肾Ⅲ型胶原蛋白表达,实时荧光定量PCR(Real-Time-PCR)法检测肾脏MT-1、MT-2 基 因表达的变化。结果:在实验过程中,氯化亚汞组4只大鼠死亡,因此未对实验数据进行统计。大鼠连续7 天给药后,药物对各组 大鼠肝、肾功能并无影响。肝脏和肾脏病理检查结果表明,孟根乌苏-18 味丸和孟根乌苏炮制品低剂量组肝细胞肿胀变性程度较 轻,肾小球轻度肥大,肾小管上皮轻度肿胀变性,孟根乌苏-18 味丸和孟根乌苏炮制品高剂量组以及硫化汞组大鼠肝脏、肾脏均出 现了一定的病理变化,而氯化汞、氯化亚汞组大鼠肝肾病理变化更显著。与正常对照组和孟根乌苏炮制品低剂量组相比,氯化汞 组大鼠肾汞蓄积量显著升高(P<0.01);硫化汞、氯化汞组大鼠肾细胞凋亡率和Ⅲ型胶原蛋白表达显著升高(P<0.01);与正常对照 组比较,氯化汞组大鼠肾组织中MT-1 和MT-2 mRNA 表达显著升高(P<0.01,P<0.05);氯化汞组大鼠肾组织中MT-1 表达显著高 于孟根乌苏炮制品低剂量组(P<0.01)。结论:临床常用量的孟根乌苏-18 味丸和孟根乌苏炮制品肝肾毒性要远低于氯化亚汞、氯 化汞。
英文摘要:
      Objective:To compare the hepatoxicity and nephrotoxicity of Meng-Gen-Wu-Su (Mercury)-18-Composition Pill, Meng-Gen-Wu-Su (Mercury) processed products and Mercuric Sulfide, Mercuric Chloride, Mercurous Chloride.Methods:Fifty-four male Wistar rats were randomly divided into nine groups according to the weight (6 rats in each group):Normal control group, low dose and high dose group (0.29 g, 2.9 g·kg-1·d-1) of Meng-Gen-Wu-Su (Mercury)-18-Composition Pill, simplified prescription of Meng-Gen- Wu-Su (Mercury)-18-Composition Pill group (0.26 g·kg-1·d-1), low dose and high dose group (0.033 g, 0.33 g·kg-1·d-1) of Meng-Gen- Wu-Su (Mercury) Processed Products, Mercuric Sulfide group(17.39 mg·kg-1·d-1), Mercuric Chloride group(4.06 mg·kg-1·d-1) and Mercurous Chloride group(35.3 mg·kg-1·d-1). After one week adaption, oral gavage was given to each group of rats for seven days. Hepatorenal function, liver and renal tissue morphological changes were detected. Mercury accumulation in kidney was determined by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Inductively Coupled Plasma Source Mass Spectrometer(ICP-MS); Apoptosis of Renal cell was determined by Terminal-Deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL); Renal Ⅲ type collagen protein expression was determined by Immunohistochemical method (HIC) and Kidney MT-1, MT-2 gene expression changes were determined by Real-Time Fluorescence Quantitative PCR(Real-Time-PCR).Results:As four rats in Mercurous Chloride group died during the experiment, there was no corresponding experimental data analysis. After seven days oral gavage, no effect on hepatorenal function was observed. Hepatic and renal pathologic examination results showed that hepatocytes of low dose groups of Meng-Gen-Wu-Su-18-Composition Pill and Meng-Gen-Wu-Su Processed Products swelled to a low degree, mild hypertrophy appeared in glomerular, and renal tubule epithelia swelled to a low degree. In high dose groups of Meng-Gen-Wu-Su Processed Products and Meng-Gen-Wu-Su-18-Composition Pill and mercuric sulfide group, liver and kidney appeared some pathological changes, but such changes were more significant in Mercuric Chloride and Mercurous Chloride groups. Compared with normal control group and low dose group of Meng-Gen-Wu-Su Processed Products, the mercury kidney volume in Mercuric Chloride group was increased significantly(P<0. 01); The renal cell apoptosis rate and Ⅲ type collagen protein expression was increased significantly in the group of Mercuric Sulfide and Mercuric Chloride(P<0.01); Compared with normal control group, MT-1and MT-2 mRNA gene expression rose significantly in the group of Mercuric Chloride(P<0.05 or P<0.01); Compared with low dose group of Meng-Gen-Wu-Su (Mercury) processed products, MT-1 mRNA gene expression rose significantly in the group of Mercuric Chloride (P<0.01).Conclusion:The hepatic and renal toxicity of Mongolian Meng-Gen-Wu-Su (Mercury)-18-Composition Pill or Meng-Gen-Wu-Su (Mercury) processed products in rats are far less than that of Mercuric Chloride or Mercurous Chloride after seven days oral gavages.
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