姜黄和乙醇对染苯小鼠CYP2E1活性及血液学毒性的影响

目的 观察染苯小鼠CYP2E1活性改变及血液学毒性的影响,继之研究乙醇、姜黄对苯毒性的干预作用.方法 昆明种小鼠80只,每组20只,随机分为4组,A组为生理盐水对照组,B组为单纯染苯组(苯中毒模型),即皮下注射苯制剂2 ml/kg;C组为乙醇干预组,即在B组处理的基础上,自由饮用10%乙醇;D组为姜黄干预组,即在给苯前,腹腔注射姜黄提取液.结果 (1)B组与A组比较,外周血及骨髓红细胞微核率上升出现高峰,同时外周血白细胞(WBC)、血红蛋白(Hb)、血小板(PLT)等指标明显低(2.6±1.0)×109/L、(93±11)g/L、(593±81)×109/L],达到了苯中毒模型的标准.(2)C组与B组比较,外周血WBC、Hb、PLT等指标均低(均P<0.05);CYP2E1活性上升显著;骨髓嗜多染红细胞微核率高于B组,且差异有统计学意义(8.8±1.8)‰比(6.5±1.0)‰,P<0.01].(3)D组与B组比较,外周血WBC、Hb、PLT数值均高(均P<0.01),但未达到正常水平;CYP2E1活性低于B组(P<0.01).结论 (1)对照比较CYP2E1活性改变后,染苯小鼠血液学毒性发生了变化;(2)乙醇诱导了CYP2E1活性,从而在体内增加了苯的血液学毒性;(3)姜黄在体内降低CYP2E1活性,一定程度上减轻了苯的血液学毒性.姜黄作为一种中药在防治苯中毒、抗炎、抗氧化、护肝及护胃等方面有着广泛的生物活性.

Preliminary effects of alcohol and curcuma longa upon CYP2E1 and hematotoxicity in benzene-induced mice

Objective To observe the effects of CYP2E1 enzymatic alteration upon hematotoxicity by benzene poisoning in mice and the interference of alcohol and cureuma longa. Methods Eighty male Kunming mice(KM) were randomly divided into four groups: group A (20 mice injected subcutaneously with sodium chloride 2 ml/kg once every 2 days for 3 weeks as normal control group); group B (20 mice injected subcutaneously with 2 ml/kg benzene once every 2 days for 3 weeks as model group); group C (20 mice drinking freely 10% alcohol per day on the basis of benzene poisoning model as alcohol-treated group) and group D (20 mice given cureuma longa 3 g/kg once a day on the basis of benzene poisoning model as curcuma-treated group). Then the blood samples were collected so as to count the parameters of WBC, Hb, PLT. In addition, the liver cytochrome P450 activity and MN formation rate were measured. Results (1) Compared with group A, WBC, Hb and PLT of group B significantly decreased (2.6±1.0)×109/L, (93±11)g/L, (593±81)×109/L]. (2) Compared with group B, the parameters of group C decreased (P<0.05) while the liver cytochrome P450 activity of group C increased. It indicated that alcohol improved the activity of CYP2E1 and the MN formation rate of group C also increased (8.8±1.8)‰ vs(6.5± 1.0)‰,P < 0.1]. (3) Compared with group B, the parameters of group D improved (P<0.01). The activity of CYP2E1 of group D decreased and the difference was significant (P<0.01). In the meantime, MN formation rate decreased (P<0.01). Conclusions (1) When the liver cytochrome P450 activity were altered, the hematotoxicity of benzene poisoning in mice underwent changes. (2) Alcohol increases the hematotoxicity induced by benzene poisoning in mice. (3) Curcuma longa has preventive effect against the hematotoxity of benzene.