Liang Tingting, Zhang Quan, Sun Weixia, Xin Ying, Zhang Zhiguo, Tan Yi, Zhou Shanshan, Zhang Chi, Cai Lu, Lu Xuemian, Cheng Mingliang
Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China; The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China; Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA.
Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China; Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA.
Toxicol Lett. 2015 Mar 4;233(2):114-24. doi: 10.1016/j.toxlet.2015.01.010. Epub 2015 Jan 21.
Whether zinc is able to improve diabetes-induced liver injury remains unknown. Transgenic type 1 diabetic (OVE26) mice develop hyperglycemia at 3 weeks old; therefore therapeutic effect of zinc on diabetes-induced liver injury was investigated in OVE26 mice. Three-month old OVE26 and age-matched wild-type mice were treated by gavage with saline or zinc at 5mg/kg body-weight every other day for 3 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level with liver histopathological and biochemical changes. OVE26 mice at 6 months old showed significant increases in serum ALT level and hepatic oxidative damage, endoplasmic reticulum stress and associated cell death, mild inflammation, and fibrosis. However, all these hepatic morphological and functional changes were significantly prevented in 3-month zinc-treated OVE26 mice. Mechanistically, zinc treatment significantly increased hepatic metallothionein, a protein with known antioxidant activity, in both wild-type and OVE26 mice. These results suggest that there were significantly functional, structural and biochemical abnormalities in the liver of OVE26 diabetic mice at 6 months old; however, all these changes could be prevented with zinc treatment, which was associated with the upregulation of hepatic metallothionein expression.
锌是否能够改善糖尿病诱发的肝损伤尚不清楚。转基因1型糖尿病（OVE26）小鼠在3周龄时出现高血糖；因此，在OVE26小鼠中研究了锌对糖尿病诱发肝损伤的治疗效果。3月龄的OVE26小鼠和年龄匹配的野生型小鼠每隔一天通过灌胃给予生理盐水或5mg/kg体重的锌，持续3个月。通过血清丙氨酸转氨酶（ALT）水平以及肝脏组织病理学和生化变化来检测肝损伤。6月龄的OVE26小鼠血清ALT水平显著升高，肝脏出现氧化损伤、内质网应激及相关细胞死亡、轻度炎症和纤维化。然而，在接受3个月锌治疗的OVE26小鼠中，所有这些肝脏形态和功能变化均得到显著预防。从机制上讲，锌治疗显著增加了野生型和OVE26小鼠肝脏中的金属硫蛋白，这是一种具有已知抗氧化活性的蛋白质。这些结果表明，6月龄的OVE26糖尿病小鼠肝脏存在显著的功能、结构和生化异常；然而，锌治疗可以预防所有这些变化，这与肝脏金属硫蛋白表达上调有关。
