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目的探讨亚急性1,2-二氯乙烷(1,2-DCE)染毒对小鼠肝微粒体中CYP2E1表达的影响及其在1,2-DCE中毒性肝损伤中的作用。方法 (1)将32只昆明种雌性小鼠随机分为对照组及1,2-DCE低、中和高剂量染毒组,染毒剂量分别为0.225、0.45和0.9 g/m3。采用静式吸入方式对小鼠染毒10 d,末次染毒的次日,处死小鼠,迅速取血和肝组织。对肝组织进行病理学观察,并检测血中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性及肝微粒体中CYP2E1蛋白表达和活性。(2)将60只昆明种雌性小鼠随机分为空白对照组、玉米油对照组、二烯丙基硫化物(DAS)对照组、单纯染毒组及低和高剂量DAS干预组(150和300 mg/kg)。将DAS溶于玉米油中,于1,2-DCE染毒前4 h通过灌胃给予DAS。1,2-DCE染毒时间及检测指标同上。结果 (1)中、高剂量染毒组小鼠肝组织出现不同程度病理性损伤;高剂量染毒组小鼠血清中ALT活性显著高于对照组(P<0.05);中、高剂量染毒组小鼠肝微粒体中CYP2E1蛋白表达和活性与对照组相比均显著升高(P<0.05)。(2)高剂量DAS干预组小鼠肝细胞病理损伤明显改善,其小鼠血清中ALT活性也显著低于单纯染毒组(P<0.05);低、高剂量DAS干预组小鼠肝微粒体中CYP2E1蛋白表达和酶活性均显著低于单纯染毒组(P<0.05)。结论 1,2-DCE染毒可明显诱导肝微粒体中CYP2E1蛋白的表达,并导致肝组织损伤,DAS通过抑制CYP2E1蛋白的表达可以减轻1,2-DCE引起的肝损伤。
Objective To investigate the effect of 1,2-DCE on the expression of CYP2E1 in mouse liver microsomes and its role in 1,2-DCE toxic liver injury. Methods (1) Thirty-two female Kunming mice were randomly divided into control group and low-, medium- and high-dose 1,2-DCE exposure groups. The doses were 0.225, 0.45 and 0.9 g / m3, respectively. The animals were exposed to static inhalation for 10 days. On the next day after the last exposure, mice were sacrificed and the blood and liver tissues were rapidly taken out. The pathological changes of hepatic tissue were observed and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the activity of CYP2E1 protein in liver microsome were detected. (2) 60 Kunming female mice were randomly divided into blank control group, corn oil control group, diallyl sulfide (DAS) control group, simple exposure group and low and high DAS intervention group (150 and 300 mg / kg). DAS was dissolved in corn oil and given to DAS by gavage 4 h prior to 1,2-DCE exposure. 1,2-DCE exposure time and detection indicators Ibid. Results (1) The liver tissues of middle and high dose groups had pathological lesions in different degrees. ALT activity in serum of high dose group was significantly higher than that in control group (P <0.05) The CYP2E1 protein expression and activity in liver microsomes of mice were significantly higher than those of the control group (P <0.05). (2) The pathological changes of hepatocytes in mice treated with high-dose DAS were significantly improved, and the ALT activity in serum of mice treated with high-dose DAS was significantly lower than that of mice exposed to DAS alone (P <0.05) CYP2E1 protein expression and enzyme activity were significantly lower than the simple exposure group (P <0.05). Conclusions 1,2-DCE can induce the expression of CYP2E1 protein in liver microsomes and lead to liver injury. DAS can reduce 1,2-DCE-induced hepatic injury by inhibiting the expression of CYP2E1 protein.