Human urinary kallidinogenase protects against cerebral ischemia reperfusion injury in mice / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of human urinary kallidinogenase (HUK) on cerebral ischemia reperfusion injury in mice.Methods One hundred and ten male ICR mice were randomly divided into sham operation,control and HUK groups.A cerebral ischemia-reperfusion model was induced by transient middle cerebral artery occlusion.The infarct volume was detected by triphenyltetrazolium chloride staining.Bcl-2,Bax,and caspase-3 expression levels in the ischemic cortex were detected by Western blot.Bcl-2 and Bax positive cells in the hippocampal CA1 area on the ischemic side were detected using Immunohistochemical staining.Apoptotic cells in the ischemic cortex were detected by TUNEL staining.Results No infarction and neurological deficits were found in the sham operation group.At 24 h after ischemia-reperfusion,the infarction voltne (P ＜0.01) and neurological deficit score (P =0.02) in the HUK group were significantly lower than those in the control group;at 72 h after ischemia-reperfusion,the infarction volume (P ＜ 0.01) and neurologic deficit score (P =0.03) in the HUK group were also significantly lower than those in the control group.Westem blot analysis showed that the expression level of Bcl-2 in the ischemic cortex in the HUK group was significantly higher than that in the control group (P ＜ 0.001),and the expression levels of caspase-3 (P ＜ 0.001) and Bax (P ＜ 0.001) in the cerebral cortex in the HUK group were significantly lower than those in the control group.No apoptotic cells were found in the sham operation group.The number of apoptotic cells in hippocampal CA1 area (P ＜ 0.01) and the number of Bax positive cells (P ＜0.01) in the HUK group were significantly less than those in the control group,while the number of Bcl-2 positive cells was significantly more in the control group (P ＜ 0.01).Conclusions HUK has a certain protective effect on ischemia-reperfusion injury in mice,its mechanism may be associated with the upregulation of Bcl-2 protein expression and downregulation of caspase-3 and Bax protein expression,thus inhibiting cell apoptosis.