Yang Yifei, Shi Ruihan, Soomro Majid H, Hu Fengjiao, Du Fang, She Ruiping
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Laboratory of Animal Pathology and Public Health, Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Front Microbiol. 2018 Mar 16;9:460. doi: 10.3389/fmicb.2018.00460. eCollection 2018.
Previous studies demonstrated that Mongolian gerbils can be infected by hepatitis E virus (HEV), which induces the hepatic injury. Here, the mitochondria in hepatocytes from HEV-infected gerbils were considerably swollen, thin cristae. After HEV infection, the activity of superoxide dismutase significantly decreased ( < 0.01), while malondialdehyde concentrations significantly increased, compared with those in the control group ( < 0.01). Adenosine triphosphatase levels decreased significantly in the hepatocyte of the inoculated groups, compared with those in control group ( < 0.05) at days 21, 28, 42 post-inoculation (dpi) as well. Furthermore, the levels of ATP synthetase ATP5A1 significantly decreased during HEV infection, compared with those in the control group ( < 0.05). According to the TdT mediated dUTP nick end labeling (TUNEL) detection, TUNEL positive hepatocytes increased in the inoculated group, compared with that in the control group ( < 0.05). Up-regulation of the mitochondrion-mediated apoptosis regulating proteins, Bax and Bcl-2, in the HEV-infected gerbils ( < 0.05) was observed. However, cytochrome c levels in mitochondria decreased, while this molecule was detected in the cytoplasm of the infected animals, in contrast to that in the control group. Apaf-1, and active caspase-9 and -3 levels were shown to be significantly higher in the inoculated group compared with those in the control group ( < 0.05). Taken together, our results demonstrated that HEV infection induces hepatocyte injuries and activity of the mitochondrial apoptotic pathway, which trigger the hepatocyte apoptosis in Mongolian gerbils.
先前的研究表明，蒙古沙鼠可被戊型肝炎病毒（HEV）感染，该病毒可导致肝损伤。在此，HEV感染沙鼠的肝细胞中线粒体明显肿胀，嵴变薄。与对照组相比，HEV感染后，超氧化物歧化酶活性显著降低（<0.01），而丙二醛浓度显著升高（<0.01）。接种组肝细胞中的三磷酸腺苷酶水平在接种后21、28、42天（dpi）时与对照组相比也显著降低（<0.05）。此外，与对照组相比，HEV感染期间ATP合成酶ATP5A1的水平显著降低（<0.05）。根据末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）检测，接种组TUNEL阳性肝细胞比对照组增加（<0.05）。观察到HEV感染沙鼠中线粒体介导的凋亡调节蛋白Bax和Bcl-2上调（<0.05）。然而，与对照组相比，感染动物细胞质中检测到该分子，而线粒体中的细胞色素c水平降低。与对照组相比，接种组中Apaf-1、活性caspase-9和-3水平显著更高（<0.05）。综上所述，我们的结果表明，HEV感染会导致肝细胞损伤和线粒体凋亡途径的激活，从而引发蒙古沙鼠的肝细胞凋亡。
