Protection against ischemia-reperfusion injury in aged liver donor by the induction of exogenous human telomerase reverse transcriptase gene

摘要

Background Liver ischemia-reperfusion (I/R) injury is of great importance in primary graft dysfunction after transplantation, and could be more severe in transplantation using aged donor livers. In order to alleviate the I/R injury in aged donor livers, we transferred exogenous human telomerase reverse transcriptase (hTERT) gene into aged rat's livers before liver transplantation. After transplantation, the effect of the gene for aged rats on cell apoptosis caused by I/R injury was evaluated. Methods The experiment was divided into 2 parts: comparative experiment between aged rats and adult rats, and exogenous induction experiment of aged rats. In the first part, Wistar rats were divided into 2 groups; group I was composed of adult rats (5 months) and group II was composed of aged rats (16-18 months). After successful transplantation, chronic oxidative stress and lipid peroxidation-related indicators (contents of vitamin C and vitamin E; activities of superoxide dismutase, catalase, and methane decarboxylic aldehyde) and alanine aminotransferase activity were examined. In the second part, additional aged rats were divided into 3 groups: group A included the donors pretreated with exogenous hTERT gene; group B included the donors pretreated with adenovirus vector; and group C was composed of the donors pretreated with physiological saline. Various indicators were detected to analyze the effect of the gene on I/R injury of the aged rats. Results The lower vitamin C, vitamin E, SOD, and CAT contents in the aged group than those in the adult group (P <.05), and the higher MDA and ALT contents in the aged group than those in the adult group (P <.05) were observed. The apoptotic index and ALT levels in the hTERT gene-pretreated group were significantly lower than those in the adenovirus vector group and the physiological saline group (P <.05). Meanwhile, mild histological injury and increased telomerase activity were also observed in the hTERT gene-pretreated group. Conclusion Compared with the adult rats, I/R injury in the aged liver donor is more severe. The induction of exogenous hTERT gene offers protection against I/R injury in the aged liver.