COX-2/sEH dual inhibitor PTUPB alleviates non-alcoholic fatty liver disease in mice by inhibiting endoplasmic reticulum stress

doi:10.13418/j.issn.1001-165x.2020.05.014

Chinese Journal of Clinical Anatomy ›› 2020, Vol. 38 ›› Issue (5) : 562-567. DOI: 10.13418/j.issn.1001-165x.2020.05.014

ZHANG Jun¹, ZHANG Chen-yu², SUN Chen-chen², TIAN Qing¹, YANG Hui-hui², LIU Yu-biao², YANG Jin-tong², ZHOU Yong², LIU Shao-kun³

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Abstract

Objective　To investigate the protective role and mechanism of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) dual inhibitor PTUPB in non-alcoholic fatty liver disease (NALFD) in mice. Methods Thirty-two male C57BL/6 mice were randomly divided into the following groups: a control group, a PTUPB group, a HFD group, and a HFD + PTUPB group. Mice in the PTUPB group and the HFD + PTUPB group were subcutaneously injected with COX-2/sEH dual inhibitor PTUPB (5 mg/kg/d). Mice in the control group and the HFD group were subcutaneously injected with PEG400. After 12 weeks, the weight change of mice was observed. HE, Oil red O, and Masson staining were used to observe liver tissue pathology morphologic changes, lipid accumulation, and collagen deposition, respectively. The protein expression of IRE-1α and XBP-1s in the liver of NAFLD mice was detected by Western blot. The expression of genes related to endoplasmic reticulum stress (Perk，Ire-1α，Xbp-1s and Aft-6) in AML-12 treated with palmitic acid (PA) was detected by Real-time PCR. Results Compared with the HFD group, the body weight and weight change rate of mice in the HFD + PTUPB group significantly reduced. The liver pathological damage, lipid accumulation, and collagen deposition significantly ameliorated, and the protein expressions of IRE-1α and XBP-1s significantly down-regulated in the HFD + PTUPB group. In vitro, PTUPB pretreatment could reduce the expression levels of genes related to endoplasmic reticulum stress in AML-12 cells PA-induced. Conclusions Dual inhibition of COX-2 and sEH attenuates HFD-induced NALFD by suppressing endoplasmic reticulum stress in mice.

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PTUPB; / / Non-alcoholic fatty liver disease; / / Endoplasmic reticulum stress

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ZHANG Jun, ZHANG Chen-yu, SUN Chen-chen, TIAN Qing, YANG Hui-hui, LIU Yu-biao, YANG Jin-tong, ZHOU Yong, LIU Shao-kun. COX-2/sEH dual inhibitor PTUPB alleviates non-alcoholic fatty liver disease in mice by inhibiting endoplasmic reticulum stress[J]. Chinese Journal of Clinical Anatomy. 2020, 38(5): 562-567 https://doi.org/10.13418/j.issn.1001-165x.2020.05.014

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