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Clin Res Hepatol Gastroenterol. 2019 Apr;43(2):161-170. doi: 10.1016/j.clinre.2017.04.009. Epub 2019 Feb 1.

Pre-treatment with FK506 reduces hepatic ischemia-reperfusion injury in rats.

Author information

1
Department of Hepatobiliary Surgery, Weifang Traditional Chinese Hospital, 261001 Shandong, China.
2
Department of hepatobiliary surgery, Tianjin First Center hospital, No. 24, Fukang road, Nankai district, 300192 Tianjin, China. Electronic address: zhangyamin@medmail.com.cn.
3
Department of hepatobiliary surgery, Tianjin First Center hospital, No. 24, Fukang road, Nankai district, 300192 Tianjin, China.

Abstract

AIM:

The study is aimed to investigate the protective effects and possible mechanism of tacrolimus (FK506) pre-treatment in hepatic ischemia-reperfusion injury in rats.

METHODS:

The rats were randomly assigned into four groups, which were S, IR, L and H group, and then all groups were subjected to 60min of 70% partial warm liver ischemia, except S group. Rats in the L and H group were pre-treated with two different doses FK506 at 60min before ischemia. The rats of the IR group received an identical volume of normal saline. All animals were sacrificed after 6h of reperfusion. Transaminases were measured by biochemistry analyzer. Elisa kit was used to detect TNF-α, IL-6 and IL-1β levels in serum. Liver specimens were stained with hematoxylin and eosin (HE) to assess the pathologic changes. The expressions of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), nuclear factor of activated T cells (NFAT3) were measured by real-time quantitative PCR and western blotting and the Bcl-2 and the Bax protein were tested by western blotting.

RESULTS:

In rats pre-treated with FK506, the levels of transaminases, TNF-α and IL-1β were reduced significantly and also liver damage was dramatically mitigated compared to those without FK506 pre-treatment. Moreover, the expression of HO-1 at the level of both transcription and translation increased clearly and the activation of the HIF-1α was found in FK506 pre-treated livers. Moreover, NFAT3 protein transportation to the nucleus was reduced and Bax protein expression was decreased, but the expression of Bcl-2 protein was markedly increased after FK506 pre-treatment.

CONCLUSION:

FK506 pre-treatment could lessen hepatic ischemia-reperfusion injury through up-regulating the expression of HIF-1α and HO-1, and inhibiting nuclear translocation of NFAT3 in liver tissues.

KEYWORDS:

FK506; Hepatic ischemia-reperfusion injury; Hypoxia-inducible factor-1α; Liver protection; NFAT3

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