褪黑素和氨基胍对锰致大鼠肝脏毒性的影响  

Effects of Melatonin and Aminoguanidin on Liver Induced by Manganese in Rat

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,辽宁沈阳110001

出　　处：《工业卫生与职业病》2008年第6期352-355,共4页Industrial Health and Occupational Diseases

基　　金：国家自然科学基金(30771834)

摘　　要：目的研究褪黑素(MLT)和氨基胍(AG)对锰致大鼠肝毒性的影响,重点观察肝脏诱导型一氧化氮合酶(iNOS)活性和一氧化氮(NO)、丙二醛(MDA)含量的改变。方法大鼠按体重随机分成4组,每组10只,第1组为对照组,第2组为单纯染锰组,第3、4组分别为MLT和AG干预组。第1和2组腹腔注射生理盐水,第3、4组分别腹腔注射MLT 5 mg/kg和AG 40 mg/kg;2 h后,第1组皮下注射生理盐水,第2、3、4组分别皮下注射MnCl2溶液200μmol/kg,注射容量5 ml/kg。每周5次,共4周。4周后,测定血清乳酸脱氢酶(LDH)、丙氨酸氨基转移酶(GPT)以及肝脏一氧化氮合酶(NOS)活性和NO、MDA含量。结果与对照组比较,单纯染锰组大鼠血清LDH和GPT的活性以及肝脏NO、MDA含量和iNOS活性明显升高,且差异有统计学意义(P<0.01);MLT干预组与单纯染锰组比较,血清LDH和GPT的活性以及肝脏NO、MDA含量和iNOS活性明显下降,且差异有统计学意义(P<0.01);AG干预组与单纯染锰组比较,血清LDH和GPT的活性以及肝脏NO含量和iNOS活性有所下降。结论锰致肝损伤与肝细胞内iNOS活性升高和产生过多的NO和MDA有关,而且MLT和AG对锰的肝毒性有一定地保护作用。Objective To observe effects of melatonin（MLT） and aminoguanidin（AG） on liver induced by Mn through measuring NO, MDA levels and iNOS activity. Methods 40 SD rats were randomly divided into four groups by weight. The first group was the control group which was intraperitoneally（i, p. ）injected with 0.9% NaCl only. The second group was i. p. injected with 0.9% NaCl. The third and fourth groups were respectively i. p. injected with MLT 5 mg/kg and AG 40 mg/kg. After two hour, the first group was given subcutaneous（s, c. ） injection of 0. 9% NaCl. The second to fourth groups were given s. c. injection of 200 umol/kg MnCl2. 4 weeks after administration, the rats were anatomized and their liver tissue samples and blood serum were collected. The LDH and GPT activities in blood serum, the activity of iNOS and the levels of NO and MDA in liver were determined. Results 4 weeks after administration, the results showed that compared with the control group the LDH and GPT activities in blood serum, the activity of iNOS, the levels of NO and MDA in liver of the MnCl2- exposed rats increased significantly. Compared with the MnCl2-exposed rats the LDH and GPT activities in blood serum, the activity of iNOS and the levels of NO and MDA in liver decreased significantly in the MLT and AG group. Conclusions Manganese-induced hepatotoxicity is related to the increase of NO and MDA levels and iNOS activity. To some extent, MLT and AG could prevent manganese-induced hepatotoxieity.

关 键 词：锰 肝毒性 褪黑素 氨基胍 

分 类 号：R994.6[医药卫生—毒理学]