尼莫地平对锰致大鼠肝脏NO和NOS改变的影响  

Effect of nimodipine on changes of NO and NOS in rat liver caused by manganese

作　　者：徐斌[1] 徐兆发[1] 邓宇[1] 关坤[1] 王飞[1] 冯雪英[1] 

机构地区：[1]中国医科大学公共卫生学院环境卫生教研室,辽宁沈阳110001

出　　处：《中国工业医学杂志》2008年第3期174-175,共2页Chinese Journal of Industrial Medicine

基　　金：国家自然科学基金(编号:30771834)

摘　　要：目的 研究尼莫地平对锰致大鼠肝毒性的影响，重点观察肝脏NO含量和iNOS活性的改变。方法 大鼠按体重随机分成5组，第1组为对照组，第2～4组为单纯染锰组，第5组为尼莫地平干预组。第1～4组腹腔注射生理盐水，第5组腹腔注射2．39μmol／L尼莫地平。2h后，第1组皮下注射生理盐水，第2～4组分别皮下注射MnCl2溶液50、100、200μmol／L，第5组皮下注射MnCl2200μzmol／L，注射容量5ml／kg。每周5次，共4周。各组处理4周后，测定血清乳酸脱氢酶（LDH）、丙氨酸氨基转移酶（ALT）以及肝组织中NO含量和iNOS的活性。结果 随着染锰剂量的增加，大鼠血清LDH和ALT的活性以及肝脏NO含量和iNOS活性逐渐升高。高剂量染锰组上述各指标均明显高于对照组和中、低剂量染锰组，且差异有统计学意义（P〈0．01）。尼莫地平干预组与高剂量染锰组比较，LDH和ALT活性以及肝脏NO含量和iNOS活性均明显下降，差异有统计学意义（P〈0．01）。结论 锰可致肝细胞内iNOS活性升高并产生大量的NO，钙离子拮抗剂尼莫地平可有效拮抗锰的肝毒性。Objective The aim of this study was to determine whether nimodipine （Nim） can prevent the toxic effect of Mn on liver by measuring NO level and iNOS activity. Methods SD rats were randomly divided into five groups by weight. The first group was the control which was only injected with 0.9% NaCl; second to fourth groups were intraperitoneally injected with MnCl2 ; and the fifth group was i.p. given Nim 2. 39 μLmol/L. Two hours later, the control group was still given 0. 9% NaCI, subcutaneously; the second to fourth groups were subcutaneously injected with 50, 100 and 200 μLmol/L MnCl2, the fifth group was given subcutaneous injection of 200 μLmol/L MnCl2. Four weeks later after administrated mentioned above, the rats were anatomized and taking the liver and serum samples for measuring the activities of LDH and GPT in serum, the iNOS activity and NO level in liver were also determined at the same time. Results The results showed that with the increase of manganese dose, the activities of LDH and GPT in serum, the iNOS activity and the NO level in liver of manganese exposed rats also increased significantly dose-dependently （P〈0. 01）. Compared with the rats given highest dosage of manganese all the changes mentioned above in Nim group were significantly decreased （P 〈0. 01 ）. Conclusion Manganese has hepatotoxicity, which could produce large amount of NO by activating iNOS; and nimodipine to a certain extent might reduce these adverse effect of manganese.

关 键 词：锰 肝毒性 尼莫地平 

分 类 号：O614.711[理学—无机化学]