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


CONCLUSIONS
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.
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
Z Y
ZY
Liu
Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, China.
W
W
Wang
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China. Electronic address: jinbin9449@126.com.
B
B
Jin
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
G Z
GZ
Li
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
G
G
Du
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
Z L
ZL
Zhang
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
L T
LT
Han
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
G Z
GZ
Huang
Department of General Surgery of Qilu Hospital, School of Medicine, Shandong University, Jinan, China.
Z Y
ZY
Tang
D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D015971:Gene Expression Regulation, Enzymologic; D016031:Liver Transplantation; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014019:Tissue Donors
D019098:Telomerase