15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy

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• 作者：Kan Chen^a ; ¹ ; ^{cutking@126.com" class="auth_mail" title="E-mail the corresponding author} ; Jingjing Li^a ; ¹ ; ^{sealjj@126.com" class="auth_mail" title="E-mail the corresponding author} ; Sainan Li^a ; ¹ ; ^{Lrk678@126.com" class="auth_mail" title="E-mail the corresponding author} ; Jiao Feng^a ; ^{fengjiao080801@163.com" class="auth_mail" title="E-mail the corresponding author} ; Liwei Wu^a ; ^{1085336378@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Tong Liu^a ; ^{klmn1334@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Rong Zhang^a ; ^b ; ^{Sylvia_rong@163.com" class="auth_mail" title="E-mail the corresponding author} ; Shizan Xu^a ; ^b ; ^{964949991@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Keran Cheng^a ; ^c ; ^{chengkeran@126.com" class="auth_mail" title="E-mail the corresponding author} ; Yuqing Zhou^a ; ^c ; ^{zyq937065339@163.com" class="auth_mail" title="E-mail the corresponding author} ; Shunfeng Zhou^a ; ^c ; ^{1374437780@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Fan Wang^a ; ^{fairywong04285@163.com" class="auth_mail" title="E-mail the corresponding author} ; Weiqi Dai^a ; ^{dai_yue@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yujing Xia^a ; ^{gagaxyj@126.com" class="auth_mail" title="E-mail the corresponding author} ; Jie Lu^a ; ^{kennisren@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Yingqun Zhou^a ; ^{yqzh02@163.com" class="auth_mail" title="E-mail the corresponding author} ; Chuanyong Guo^a ; ^{guochuanyong@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：15-Deoxy-Δ12 ; 14-prostaglandin J2 ; Concanavalin A ; HO-1 ; Autophagy ; Nrf2
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：80
• 期：Complete
• 页码：183-192
• 全文大小：6079 K

文摘

In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism.

Materials and methods

Balb/C mice were injected with ConA (25 mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5–10 μg) was administered 30 min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8 h after the ConA injection.

Results

Following ConA challenge, the expression of cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-α, IL-1β and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation.

Conclusion

15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS.