Pemafibrate Pretreatment Attenuates Apoptosis and Autophagy during Hepatic Ischemia-Reperfusion Injury by Modulating JAK2/STAT3β/PPARα Pathway

Hepatic ischemia-reperfusion injury (HIRI) is a common phenomenon in liver transplantation and liver surgery. This article is aimed at clarifying the role of pemafibrate in HIRI through JAK2/STAT3β/PPARα. In the experiment, we divided Balb/c into seven groups, namely, normal control (NC), Sham, PEM (1.0 mg/kg), IRI, IRI + PEM (0.1 mg/kg), IRI + PEM (0.5 mg/kg), and IRI + PEM (1.0 mg/kg). We used biochemical assay, histopathological evaluation, immunohistochemistry, RT-PCR and qRT-PCR, ELISA analysis, and other methods to determine the level of serum AST, ALT, IL-1β, and TNF-α in the liver at three time points (2 h, 8 h, and 24 h) after reperfusion of apoptosis factor, autophagy factor, and the JAK2/STAT3/PPARα content in tissues. Our experiment results showed that the pemafibrate can effectively reduce the level of hepatic IR injury. In addition, pemafibrate has anti-inflammatory, antiapoptotic, and antiautophagy effects, which are mediated by the JAK2/STAT3β/PPARα pathway.

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Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78

Bioscience Reports ◽

10.1042/bsr20180549 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 1

Author(s):

Di Liu ◽

Xin Jin ◽

Chunqi Zhang ◽

You Shang

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Regulatory Protein ◽

Liver Homogenate ◽

Hepatic Ischemia ◽

Damage Degree ◽

Tnf Α ◽

Hepatic Ischemia Reperfusion

Purpose: This article aimed to study the role of sevoflurane pre-conditioning in hepatic ischemia–reperfusion and its potential mechanism. Methods: Rat liver ischemia–reperfusion model was constructed. Serum TNF-α, IL-1β, IL-10, and IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined. Hematoxylin–Eosin (HE) staining, Tunel, and immunohistochemistry were performed. Ischemia–reperfusion hepatocyte model was established. Cells transfection was conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR (qRT-PCR) and Western blotting analysis were used. Results: Compared with I/R group, liver damage degree, liver cell apoptosis, and glucose regulatory protein 78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-α, IL-1β, and IL-6 concentrations were also significantly increased (P<0.01). MDA and NO concentrations were dramatically lower (P<0.01) and SOD concentration was significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2α, and p-c-JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane significantly reduced apoptosis and expression of PERK, eIF2α, p-c-JNK/JNK by inhibiting the expression of Grp78 (P<0.01). Conclusion: Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78.

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