关键词: 脑缺血, 再灌注损伤, 热休克蛋白质70

Abstract: Objective To investigate the effects of Lidocaine on the expressions of HSP70 mRNA and HSP70 protein in cerebral cortex during transient focal cerebral ischemia-reperfusion in rats, and to discuss the possible mechanisms of its neuroprotection. Methods Sixty male Wistar rats weighing 250-300 g were randomly divided into 3 equal groups: sham operation group undergoing sham operation; ischemia/reperfusion (I/R) group undergoing thread embolism of the left middle cerebral artery occlusion (MCAO) to cause focal ischemia for 2 h and then undergoing reperfusion; and lidocaine group undergoing intravenous injection of Lidocaine in doses of 10 mg·kg^-1 10 min before MCAO. At 3, 6, 24, and 72h after reperfusion the rats were decapitated, the expressions of HSP70 mRNA and HSP70 protein in ischemic versus nonischemic cortex were examined using in situ hybridization and immunohistochemistry. At the 24 h after reperfusion, scores of neurological deficit were estimated and changes of histomorphology in ischemic cortex were observed under the light microscope by using HE staining. Results The expressions of HSP70 mRNA and HSP70 protein in ischemic cortexes in the I/R group 3 to 72 h after reperfusion increased significantly, and the peak value of their expression was 161.5±4.8 and 160.9±4.8, respectively, significantly higher than those in the sham operation group (all P<0.01). The expression of HSP70 mRNA appeared early and had a wide distribution in ischemic cerebral hemisphere. Whereas, the expression of HSP70 focused in ischemic cortex. The score of neurological deficit in rats in I/R group was 2.28±0.47, significantly higher than that in the sham operation group (P<0.01). Congestion and edema in ischemic cortex, degeneration and necrosis of neuron were observed in histomorphology in I/R group. Intravenous injection of Lidocaine enhanced significantly the expressions of HSP70 mRNA and HSP70 protein in ischemic cortex 3 to 72 h after reperfusion. The peak values of HSP70 mRNA and HSP70 protein expression in the Lidocaine group were 178.6±5.6 and 176.2±4.7, respectively, significantly higher than those in the I/R group (all P<0.01). The scores of neurological deficit and the damage of histomorphology in the lidocaine group were significantly lower than those in I/R group (all P<0.05). Conclusion Lidocaine can enhance the expressions of HSP70 mRNA and HSP70 protein during focal cerebral ischemia-reperfusion. This may be one of the mechanisms of its neuroprotection.

Key words: brain ischemia, reperfusion injury, heat-shock proteins 70