硫酸锌诱导金属硫蛋白2表达对脓毒症小鼠脏器损伤的保护作用

A Study on the Protective Effect of the Metallothionein-2 Expression Induced by Zinc Sulfate on the Visceral Organs of Mice with Sepsis

目的研究硫酸锌对金属硫蛋白2(MT2)表达的诱导效应及其对脓毒症小鼠脏器损伤的保护作用。方法选取健康的6~8周龄雄性C57/6小鼠36只,随机分成假手术组、脓毒症组及硫酸锌干预组,每组12只,观察3组小鼠经不同方法处理后的基本情况。使用ELISA法检测每组小鼠血清中MT2、TNF-α、白介素6(IL-6)、超氧化物歧化酶(SOD)、丙二醛(MDA)浓度,肝组织蛋白质印迹法观察MT2表达量,显微镜下观察肺、肝、小肠组织的病变情况,TUNEL法计算各器官细胞凋亡指数。结果硫酸锌干预组小鼠死亡率低于脓毒症组;MT2表达量及SOD浓度明显高于脓毒症组及假手术组,差异有统计学意义(P<0.05);脓毒症组小鼠血清炎症因子及MDA水平明显高于其他两组,差异有统计学意义(P<0.05);显微镜下观察显示:硫酸锌干预组各脏器细胞变性坏死及凋亡程度均轻于脓毒症组。结论锌离子可以诱导C57/6小鼠MT2的表达,降低血清炎症因子的水平,降低血清MDA含量、提高SOD活性,减轻各脏器组织病理性损伤,降低脓毒症小鼠死亡率。

Objective To investigate the inductive effect of zinc sulfate on the metallothionein-2（MT2） expression and the protective effect of the MT2 expression on the multiple organ damage in mice with sepsis.Methods Thirty-six healthy male C57/6mice with the age of 6 to 8 weeks were randomly divided into three groups including the sham surgery group,sepsis group and intervention group,and each group consisted of 12 mice.The basic situations of the mice in the three groups were observed after they were given different treatments.ELISA was used to detect the levels of MT2,TNF-α,IL-6,IL-10,MDA,SOD and MDA in serum.Western blotting was employed to observe the levels of MT2 in liver.HE staining was adopted to examine the morphologic changes of multiple organs.The lesions in lung,liver and intestine were detected and their apoptosis indexes were calculated by TUNEL.Results The mortality rate of the mice in the intervention group was lower than that of the sepsis group,while the expression levels of MT2 and SOD in the intervention group were significantly higher than the those in the sepsis and sham operation groups respectively（P〈0.05）.The levels of inflammatory cytokines and MDA in the sepsis group were significantly higher than those in the other two groups（P〈0.05）.Meanwhile,The levels of cell degeneration,necrosis and apoptosis in the intervention group were lower than those in the sepsis group in the microscope.Conclusion Zinc ions could induce the expression of MT2,reduce release of the inflammatory factors and the content of MDA in serum,increase the SOD activity,reduce the pathological damage of organs in mice,and increase the survival rate of mice with sepsis.