Mechanism and effect of metformin on inflammatory cytokines in rats with cerebral ischemia-reperfusion injury

Objective To investigate the effect and mechanism of metformin on inflammatory cytokines after cerebral ischemia-reperfusion injury in rats. Methods A rat model of middle cerebral artery occlusion (MCAO) was established by suture method. The neurological function was evaluated by modified neurological function score (mNSS). The apoptosis was detected by TUNEL method. The levels of interleukin-6 (IL-6), interleukin-8(IL-8) and tumor necrosis factor alpha (TNF-α) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of hypoxia inducible factor-1α(HIF-1α), BAX and BCL-2 protein in brain tissue was detected by Western Blot. Results Compared with the control group, the neurological function scores and the tissue cell apoptosis of the rats with cerebral ischemia injury was both significantly increased (all P<0.01). Compared with the model group, metformin could alleviate the rats' neurological damage after cerebral ischemia-reperfusion, and the expression of IL-6, IL-8 and TNF-α in serum were significantly decreased (all P<0.01). The expression of HIF-1α and BAX proteins were significantly down-regulated and the BCL-2 protein was up-regulated by metformin in rat brain tissue so as to regulate the expression of apoptosis-related proteins and reduce the apoptosis of brain tissue cells. Conclusions Metformin can reduce the expression of inflammatory cytokines and inhibit the apoptosis, which may play a protective role for cerebral ischemia-reperfusion injury. The mechanism may be related to the regulation of apoptosis-related protein expression, inhibition of HIF-1α expression, and inhibition of the release of related inflammatory factors TNF-α, IL-6 and IL-8. Key words: Metformin; Cerebral ischemia reperfusion; Hypoxia inducible factor-1α; Inflammatory cytokines