Ischemic tolerance phenomenon from an approach of energy metabolism

从能量代谢途径观察缺血耐受现象

基本信息

批准号：
06454281
负责人：
KATAYAMA Yasuo
金额：
$ 0.32万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454281/
关键词：
ischemic tolerance energy matabolism pyruvate dehydrogenase (PDH)protein synthesis

项目摘要

The effect of 5 min lethal ischemia on cerebral metabolism and a mitochondrial enzyme, pyruvate dehydrogenase (PDH) activity in the animals treated with or without 2 min sublethal ischemia was studied using mongolian gerbils. Protein synthesis was also studied.The animals with or without pretreatment were induced 5 min lethal ischemia and allowed reperfusion for designated periods. The pretreated animals were given 2 min ischemia 24 hr prior to 5 min ischemic insult.Brain metabolites of ATP,PCr and lactate and PDH activity were determined in the cortex and hippocampus mainly including CA_1 region. Protein synthesis was determined by autoradiography method ; after injecting [^<14>C]-leucine the uptake was measured in CA_1, CA_3', dentate and cortex in the both groups.In 10 min reperfusion lactate levels in the non-pretreated group were lower than those of the pretreated group in cortex, otherwise, there was no difference in metabolism between the pretreated and the non-pretread animals … More in the both areas by reperfusion 3 days. However, the elevation of PDH activity in the hippocampus in the pretreated animals was suppressed in 5 min ischemia. In reperfusion 7 days, marked decrease of ATP and PCr concentrations in hippocampus in the non-pretreated animals, which reflects delayd neuronal death, was noticed, while that in cortex was not noticed.Protein synthesis in the all areas measured markedly decreased compared to each sham controls 1 hr after ischemia. After 1 day, in CA_1 region, protein synthesis in the pretreated animals recovered to 50% of the control, while that in the non-pretreated was about 20% of the control. In other areas protein synthesis quickly recovered to more than 60% of the control in the both groups.In conclusion, the pretreatment of sublethal ischmia prior to lethal ischemia does not influence the degree of the secondary ischemic insult. However it may have some effect on cellar organ molecular activity like a mitochondrial enzyme PDH,and influences protein synthesis in CA_1 region, which may be essentials to induce ischemic tolerance. Less

5分钟致死性缺血对使用蒙古gerbils研究的动物中，对脑部代谢和线粒体酶，丙酮酸脱氢酶（PDH）活性的影响。蛋白质合成也是研究的。具有或没有预处理的动物被诱导5分钟致死性缺血，并允许在指定期间再灌注。预处理的动物在5分钟缺血性损伤之前24小时给予2分钟的缺血。在主要包括CA_1区域，在皮质和海马中确定了ATP，PCR和lacate的脑代谢物，并确定PDH活性。蛋白质合成是通过放射自显影法确定的。在注射[^<14> c] - 蛋白后，在CA_1，Ca_3'，Ca_3'，齿状和皮质中测量的摄取在两组中。在10分钟的未经培养组中，在10分钟的再灌注乳酸水平中，lacta酸盐水平低于比预处理中的预定动物，否则在不适合的情况下，没有预定的三个地区的差异……而不是预定的3个。但是，在5分钟的缺血中抑制了预处理动物中海马中PDH活性的升高。在7天的再灌注中，指出了未经预测的动物中海马中ATP和PCR浓度的明显降低，这反映了神经元死亡的延迟，而在皮质中没有注意到皮质中的蛋白质合成。与每一个假手术后1小时相比，所有面积的蛋白质合成。 1天后，在CA_1区域中，预处理动物中的蛋白质合成恢复到对照的50％，而在未进行的对照中，蛋白质的合成约为对照的20％。在其他地区，蛋白质合成在两组中迅速恢复到60％以上。总之，在致死性缺血之前对余心缺血的预处理不影响继发性缺血性损伤的程度。然而，它可能会对地窖有机分子活性（例如线粒体酶PDH）产生一定的影响，并且会影响Ca_1区域中的蛋白质合成，这可能是诱导缺血性耐受性的必不可少的。较少的