线粒体钙单向转运体在大鼠脑缺血再灌注损伤中的作用及其机制

The role of mitochodrial calcium uniporter on cerebral ischemia reperfusion injury in rats

目的观察线粒体钙单向转运体在大鼠脑缺血/再灌注(I/R)损伤中的作用及其机制。方法将40只雄性Wistar大鼠随机分为4组:A组(假手术组)、B组(脑缺血再灌注组)、C组(脑缺血再灌注+钌红组)、D组(脑缺血再灌注+精胺组),采用线栓法建立大鼠大脑中动脉闭塞(MCAO)模型,各组在脑缺血2h后进行再灌注,再灌注24h后观察各组大鼠神经功能评分,检测各组血清脂质过氧化产物丙二醛(malondial-dehyde,MDA)的含量、血清乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)的活性,免疫组化检测皮质区Caspase-3阳性细胞数的变化。结果 B、C、D组神经功能评分升高,血清MDA的含量以及LDH活性显著高于A组,SOD活性与A组相比显著降低,caspases-3表达细胞与A组相比明显增多。C组能明显改善上述结果,而D组相反。结论抑制线粒体钙单向转运体可以明显减轻脑缺血再灌注损伤,其机制可能与减少氧自由基产生、维护线粒体功能有关。

Objective To investigate the effect of mitochondrial calcium uniporter on cerebral ischemia/reperfusion（I/R）.Methods The I/R models of rats were performed by thread embolism of middle cerebral artery for 2 h of reperfusion.40 rats were randomly divided into four groups： sham-operated group,ischemia group,ruthenium red group and spermine group.After 24 h of reperfusion,neurological score,content of malondialdehyde（MDA）,activities of lactate dehydrogenase（LDH） and superoxide dismutase（SOD） content in serum and the changes of positive cells in cortex contained Caspase-3 protein by immunohistochemistry were observed in the above groups respectively.Results The neurological score of the last three groups increased,serum MDA and LDH was higher than the group,and SOD was lower.Immunohistochemistry showed that the expression of caspases-3 cells significantly increasd compared with the sham-operated group.Ruthenium red,which was the inhibition of MCU,could significantly change the results while the opposite result were found in spermine group.Conclusions The inhibition of mitochondrial calcium uniporter can significantly protect the rat＇s brain by reducing the oxygen free radicals,maintaining mitochondrial function.