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目的研究硫酸镍+重铬酸钾联合染毒对小鼠肝脏损伤的影响及金属硫蛋白(MT)的拮抗作用。方法将50只健康SPF级昆明小鼠按体重随机分为5组,分别为溶剂对照组(生理盐水)、镍铬(1.0 mg/kg硫酸镍+0.5 mg/kg重铬酸钾)联合染毒组和低、中、高剂量MT保护(1.0 mg/kg硫酸镍+0.5 mg/kg重铬酸+5.0、10.0、20.0 mg/kg MT)组,每组10只,雌雄各半。采取灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次,连续染毒21 d。检测小鼠丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)活力及肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)、谷胱甘肽(GSH)含量。结果与溶剂对照组比较,镍铬联合染毒组小鼠血清AST、ALT、GGT的活力均增高,差异均有统计学意义(P<0.05)。各剂量MT保护组小鼠血清AST、ALT、GGT的活力均低于镍铬联合染毒组,差异均有统计学意义(P<0.05);且随着MT染毒剂量的升高,MT保护组小鼠血清AST、ALT、GGT的活性均呈下降趋势。与溶剂对照组比较,镍铬联合染毒组小鼠肝组织SOD、GSH-Px活力和GSH含量均下降,而MDA含量升高,差异均有统计学意义(P<0.05)。与镍铬联合染毒组比较,各剂量MT保护组小鼠肝组织SOD、GSH-Px活力和GSH含量均升高,而MDA含量均降低,差异均有统计学意义(P<0.05),且随着MT染毒剂量的升高,MT保护组小鼠肝组织SOD、GSH-Px活力和GSH含量均呈上升趋势,而MDA含量呈下降趋势。结论 MT对镍铬联合染毒所致小鼠肝脏损伤有较好的拮抗作用,其作用机制可能与MT抗氧化作用有关。
Objective To study the effects of combined treatment of nickel sulfate and potassium dichromate on hepatic injury in mice and the antagonism of metallothionein (MT). Methods Fifty healthy Kunming SPF Kunming mice were randomly divided into five groups according to body weight: solvent control group (saline), nickel chromium (1.0 mg / kg nickel sulfate + 0.5 mg / kg potassium dichromate) Group and low, medium and high dose MT protection (1.0 mg / kg nickel sulfate +0.5 mg / kg dichromic acid +5.0,10.0,20.0 mg / kg MT) group, 10 in each group, male and female. Take gavage way of exposure, exposure capacity of 10 ml / kg, 1 times a day, continuous exposure to 21 d. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) and the activity of superoxide dismutase (SOD) The activity of GSH-Px and the contents of malondialdehyde (MDA) and glutathione (GSH) were determined. Results Compared with the solvent control group, the activities of AST, ALT and GGT in the Ni-Cr combined group were significantly increased (P <0.05). The activities of AST, ALT and GGT in serum of mice in each dose of MT protection group were lower than that of the combination of nickel and chromium, the differences were statistically significant (P <0.05). With the increase of MT dose, MT protection Serum AST, ALT, GGT activity of mice showed a downward trend. Compared with the solvent control group, the activity of SOD, GSH-Px and the content of GSH in the liver of the Ni-Cr combined treatment group decreased, but the content of MDA increased, the difference was statistically significant (P <0.05). Compared with the Ni-Cr combined exposure group, the activities of SOD, GSH-Px and GSH in the liver of the mice in each dose of MT group increased, while the contents of MDA in the liver were decreased (P <0.05) With the increase of MT exposure, the activities of SOD, GSH-Px and GSH in the liver of MT group increased and the content of MDA decreased. Conclusion MT has a good antagonistic effect on liver injury induced by Ni-Cr combined exposure in mice, and its mechanism may be related to the anti-oxidative effect of MT.