Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats.
OBJECTIVE
To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).


METHODS
The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes.


RESULTS
Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter group.


CONCLUSIONS
This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Dan-Dan
DD
Gao
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Jia
J
Fu
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Bo
B
Qin
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Wen-Xiang
WX
Huang
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Chun
C
Yang
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Bei
B
Jia
D065290:Acute-On-Chronic Liver Failure / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D005688:Galactosamine; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D015398:Signal Transduction; D013997:Time Factors
C422455:ALB protein, human; D051017:Apoptosis Regulatory Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D012709:Serum Albumin; D017228:Hepatocyte Growth Factor; D005688:Galactosamine; D005620:Freund's Adjuvant; D000075462:Serum Albumin, Human
Acute-on-chronic liver failure; Hepatocyte growth factor; Hyper-interleukin-6; Inflammatory cytokines; Recombinant adenovirus