Efficacy of berberine in preventing brain injury induced by hepatic ischemia-reperfusion in mice:the relationship with GSK-3β activity / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the efficacy of berberine in preventing brain injury induced by hepatic ischemia-reperfusion ( I∕R) and the relationship with glycogen synthase kinase 3 beta ( GSK-3β) activity in mice. Methods Forty-eight healthy clean-grade male C57BL∕6 mice, weighing 20-25 g, were randomized into 3 groups (n=16 each) using a random number table method: sham operation group (S group), hepatic I∕R group (I∕R group) and berberine group (B group). The model of 70％ liver I∕R injury was established by clamping the portal vein and hepatic artery supplying left and middle lobes of the liver in mice anesthetized with 2％ pentobarbital sodium 40 mg∕kg. In B group, berberine 50 mg∕kg was adminis-tered through a gastric tube once a day for 7 consecutive days starting from 7 days before operation. The e-qual volume of normal saline was given instead in S group and I∕R group. The mice were sacrificed at 6 h af-ter reperfusion, brains were removed and hippocampal tissues were harvested for microscopic examination of pathological changes ( with a light microscope) and for determination of cell apoptosis ( by TUNEL) , super-oxide dismutase ( SOD ) activity ( by xanthine oxidase method ) , malondialdehyde ( MDA ) content ( by thiobarbituric acid colorimetric method) , expression of phosphorylated GSK-3β ( p-GSK-3β) and GSK-3β(by Western blot), and opening of mitochondrial permeability transition pore (mPTP). The apoptosis in-dex and p-GSK-3β∕GSK-3β ratio were calculated. Results Compared with S group, the apoptosis index and MDA content were significantly increased, SOD activity and p-GSK-3β∕GSK-3β ratio were decreased, and mPTP opening was increased in I∕R and B groups ( P<0. 05) . Compared with group I∕R, the apoptosis index and MDA content were significantly decreased, SOD activity and p-GSK-3β∕GSK-3β ratio were in-creased, mPTP opening was decreased (P<0. 05), and the pathological changes of hippocampal tissues were significantly attenuated in B group. Conclusion Berberine can prevent the brain injury induced by he-patic I∕R, and the mechanism may be related to inhibiting GSK-3βactivity and thus inhibiting mPTP open-ing in mice.