| Objective: To determine the therapeutic efficacy of recombinant adenovirus containing HIL-6 and HGF(Ad-HGF-HIL-6) on acute-on-chronic liver failure(ACLF) in rats using that of recombinant adenovirus HIL-6 or HGF(Ad-HIL-6 or Ad-HGF) for comparison.Methods: Ad-HGF-HIL-6, Ad-HIL-6 and Ad-HGF were constructed. The ACLF rats were randomly divided into: uninfected(model) group, Ad0(control vector without the gene of interest) group, Ad-HGF group, Ad-HIL-6 group, Ad-HGF-HIL-6 group. Adenoviruses were administered by caudal vein injection subsequently. Meanwhile, the rats of the control and model groups received physiological saline of an equal volume by tail intravenous injection. The sera and liver tissues were collected for biochemical, pathological and molecular biological examinations at 24 h after adenoviruses were administered.Results: Compared with Ad0 group, plasma prothrombin time(PT), the serum levels of alanine aminotransferase(ALT), tumor necrosis factor-α(TNF-α), interferon-α(IFN-γ) and high mobility group box-1(HMGB1) markedly reduced in the ACLF rats treated with Ad-HGF, Ad-HIL-6 and Ad-HGF-HIL-6 respectively, similarly, reduced hepatic damages and apoptotic activity, as well as reduced Bax at protein levels, and increased expression of Ki67 and Bcl-2 at protein levels were observed. A greater effect in reducing serum levels of TNF-α of ACLF rats was observed from the administration of Ad-HGF-HIL-6 compared to Ad-HIL-6, among other indexes, treatment with Ad-HGF-HIL-6 showed the most significant therapeutic efficacy without obvious side effects.Conclusion: The therapeutic efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 alone on ACLF rats with no significant side effects. This research shows that Ad-HGF-HIL-6 has potential clinical application prospect and is expected to be a new gene-based drug for the treatment of ACLF. |
PDF Full Text Request