瑞芬太尼
MAPK/ERK通路
细胞周期蛋白D1
下调和上调
肝再生
药理学
细胞生物学
再生(生物学)
化学
激酶
医学
生物
细胞凋亡
生物化学
细胞周期
异丙酚
基因
作者
Ling Zhu,Yanyu Zhou,Zhi Zhang,Suqing Yin,Dongdong Lv,Yu-Ling Wu,Bao-Shan Wang,Menghan Mao,Yingfu Jiao,Weifeng Yu,Po Gao,Liqun Yang
标识
DOI:10.1016/j.bbrc.2021.04.008
摘要
Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 μg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of β-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific β-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a β-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.
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