Influence Of 2DG On Neuron Apoptosis And Expression Of Caspase-9 And Caspase-12 Of Neuron In Fetal Distress Rat

Objective The present study was undertaken to evalute the relationship of caspase-9,-12, GRP78 and neuron apoptosis. We also investigated the protective role of 2-deoxyglucose , which is a inducer of GRP78. Methods (1) Establish intrauterus distress model with SD pregnant rat. (2)The pregnant rats were divided into four groups: normal group, sham operation control group, ischemia-reperfusion group and 2-deoxyglucose treatment group. (3) To observe the cerebral pathological changes, the light microscope and electron microscope method was used to detect changes in hippocampus CA1 area of rat, which experienced hypoxia-ischemia-reperfusion in uterine or were given 2-deoxglucose. Detecting the expression of caspase-9,-12 and GRP78 protein in hippocampal CA1 area, and observing the influence of 2- deoxglucose on those protein. Results (1) There were only a few damaged and apoptotic neurons in normal group and sham control groups. The brain of fetal rat, which experienced hypoxia-ischemia-reperfusion damage in uterus, occurred various degree damage and apoptosis. With the progression of reperfusion, the number of lesion cell and the apoptotic pyramidal cell in hippocampus CA1 area became much more abundant. The Lesion- index of neurons in IR Ⅴ group was significantly more(31.6±4.7), than these in ischemia-reperfusion Ⅰgroup(P<0.01). The number of pyramidal cell became plentiful gradually with the progression of reperfusion. And that in IR Ⅴ group was significantly more significantly (97.3±8.9),than anyother group.On the contrary, the number of vital neurons decreased gradually, and was significantly decreased in IR Ⅴ group(151±14). (2) GRP78, caspase-9 and caspase-12 genes expressed in all IR groups. The AIOD of GRP78 in IR Ⅱ is significantly higher (0.48±0.16), than anyother group(P<0.01).The expression of caspase-12 increased rapidly after 3 hours from the reperfusion. Subsequently, it rising slowly .Th intensity of caspase-12 was significantly increased in IR Ⅳ group(0.59±0.16). Furthermore, caspase-9 increased very little in IR Ⅱ group. Subsequently, its expression increased rapidly. Same as caspase-12, it increased significantly in IR Ⅳ group(0.68±0.01). The lesion-index and apoptotic cell neuron in 2-deoxglucose treatment group was less than that of IR group((P<0.01). IR damage increased caspase-9,-12 expression in neuron, which could be inhibited by 2-deoxglucose. Conclusions Intrauterine ischemia-reperfusion injury in perinatal period could induce neuron apoptosis, in association with expression of caspase-9,-12. 2-deoxglucose could increase expression of GRP78, and decrease neuron apoptosis in the rat's brain, which experienced ischemia-reperfusion, and this result was possibly mediated by up-regulation of GRP78 gene expression.