Berberine preconditioning protects against hepatic cold ischemia reperfusion injury through the modulation of PI3K/Akt/mTOR signaling pathway
10.3760/cma.j.issn.0254-1785.2015.01.009
- VernacularTitle:小檗碱预处理激活PI3K/Akt/mTOR信号通路减轻大鼠肝脏冷缺血再灌注损伤
- Author:
Mingwei SHENG
;
Yuan ZHOU
;
Wenli YU
;
Yiqi WENG
;
Hongyin DU
- Publication Type:Journal Article
- Keywords:
Berberine;
Repurfusion injury;
Apoptosis;
Mammalian target of rapamycin
- From:
Chinese Journal of Organ Transplantation
2015;36(1):34-39
- CountryChina
- Language:Chinese
-
Abstract:
Objective To confirm the protective effect of berberine (BBR) on cold ischemia reperfusion (I/R)-induced liver injury and to show whether the hepatic protection conferred by BBR involves the activation of phosphatidylinositol 3 kinase (PI3K) / protein kinase B (Akt)/mammalian target of rapamycin(mTOR) signal pathway.Method Adult male Sprague-Dawley rats were assigned randomly to four groups:BBR group (BBR was intragastrically administered at a dose of 100 mg·kg-1 · d-1 2 weeks before hepatic cold I/R treatment),dimethyl sulfoxide (DMSO) group (BBR was replaced by DMSO,and others were the same as BBR group),I/R group (BBR was replaced by normal saline,and others were the same as BBR group) and sham group (normal saline was administered 2 weeks before opening and closing abdomen treatment).Then the rats were sacrificed at 3,6,and 24 h after reperfusion.The liver function,oxidative stress level,apoptosis rate,and the expression of PI3K/Akt/mTOR related pathway proteins were assayed.Result As compared with sham group,the I/R-induced liver tissue displayed severe lobular distortion with widespread necrosis,high level of oxidative stress and apoptosis rate.As compared with I/R group,BBR dramatically attenuated the histopathologic damage,restored the liver function and decreased the oxidative stress level.Simultaneously,BBR significantly ameliorated the apoptosis by decreasing the apoptosis rate,increasing the Bcl-2/Bax ratio and inhibiting caspase-3 activity in rats subjected to hepatic I/R.The expression of p-Akt was effectively upregulated with the inhibited expression of p-mTOR.Conclusion Our result provides robust in vivo evidence that BBR can prevent I/R-induced oxidative stress and apoptosis.The mechanisms involved can be attributed to the activation of P]3K/Akt/mTOR signal pathway.
