Effects and related mechanism of overexpression of human thioredoxin on the inflammatory response in mice with viral myocarditis
10.3760/cma.j.issn.0253-3758.2018.06.007
- VernacularTitle: 人硫氧还蛋白基因表达对病毒性心肌炎小鼠心肌炎症反应的影响及其机制
- Author:
Yubo GUO
1
;
Lingwang ZHOU
;
Fulai CHEN
;
Ning ZOU
Author Information
1. Second Medical School of Harbin Medical University, Harbin 150081, China
- Publication Type:Journal Article
- Keywords:
Myocarditis;
Thioredoxins;
Inflammation
- From:
Chinese Journal of Cardiology
2018;46(6):444-449
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effects of recombinant adenovirus with human thioredoxin (hTRX) on the inflammatory response in mice with viral myocarditis and explore the related mechanism.
Methods:Sixty Balb/c male mice were randomly divided into control group, myocarditis group, and hTRX group according to the random number table (n=20 each group). The myocarditis group and hTRX group were injected with 100 TCID50 Coxackie virus B3 (0.1 ml) in the abdomen and control group were injected with saline. Two days before the viral injection, the hTRX group were injected with recombinant adenovirus vector coding the human thioredoxin gene by pericardial puncture and the control group and myocarditis group were injected with recombinant adenovirus vector without coding gene by pericardial puncture, all these mice were killed and hearts were removed 7 days later. The morphology of myocardial tissue in each group was detected by HE staining and the ultrastructure changes by electron microscope. The protein expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and NF-κB were detected by ELISA and Western blot. Immunohistochemical staining was performed to observe the protein expression levels of thioredoxin.
Results:Necrosis of myocardial cells and a small amount of cell infiltration were found in the myocarditis group and necrosis and cell infiltration were significantly reduced in the hTRX group and no myocardial lesion was found in control group on HE stained sections. Electron microscope examination evidenced cell swelling and dissolved myofilament, vacuoles degeneration in mitochondria in the myocarditis group. These changes were significantly reduced in the hTRX group. There was no myocardial lesion in control group. The protein expression of TNF-α, IL-1β and NF-κB were significantly upregulated in myocarditis group than in control group (all P<0.01). The protein expression of TNF-α, IL-1β and NF-κB were significantly downregulated in hTRX group than in myocarditis group (all P<0.01). Immunohistochemical staining showed that protein expression of hTRX was higher in hTRX group than in myocarditis group (P<0.01).
Conclusion:Recombinant adenovirus hTRX can attenuate cardiac injury in mice with acute myocarditis via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-1β and NF-κB.
