Ischemic tolerance phenomenon from an approach of energy metabolism

从能量代谢途径观察缺血耐受现象

• 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

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

以蒙古沙鼠为实验动物，研究了2 min亚致死缺血对脑代谢和线粒体酶丙酮酸脱氢酶（PDH）活性的影响。蛋白质合成也进行了研究。经预处理或未经预处理的动物均被诱导5分钟的致死缺血，并在指定时间内进行再灌注。预处理动物在5分钟缺血损伤前24小时给予2分钟缺血。在以CA_1区为主的皮质和海马区检测脑代谢产物ATP、PCr、乳酸和PDH活性。用放射自显影法测定蛋白质合成；注射[^<14>C]-亮氨酸后，测定两组大鼠CA_1、CA_3′、齿状体和皮质的摄取情况。在再灌注10 min时，未预处理组的皮质乳酸水平低于预处理组，而在再灌注3 d时，预处理组与未预处理组的代谢无差异。然而，预处理动物海马PDH活性的升高在缺血5min时受到抑制。再灌注7 d时，未预处理大鼠海马区ATP和PCr浓度明显降低，反映神经元死亡延迟，而皮质区ATP和PCr浓度未见明显下降。缺血1小时后，所有测量区域的蛋白质合成均明显降低。1 d后，预处理组CA_1区蛋白质合成恢复到对照的50%，未预处理组CA_1区蛋白质合成恢复到对照的20%左右。在其他方面，两组的蛋白质合成迅速恢复到对照组的60%以上。综上所述，在致死性缺血之前进行亚致死性缺血预处理对继发性缺血损伤的程度没有影响。然而，它可能对线粒体酶PDH等细胞器官的分子活性有一定影响，并影响CA_1区蛋白质的合成，这可能是诱导缺血耐受的必要条件。少

项目成果

Katayama Y et al.: "Studies of ischemic tolerence -An approach from erergy metabolism and protein synthesis-." Jpn J Stroke. 17 (in press). (1996)

Katayama Y 等人：“缺血耐受性的研究 - 来自能量代谢和蛋白质合成的方法 -”。

yasuo KATAYAMA: "Ischemic tolerance phenomenon from an approach of energy metabolism and the mitochondrial enzyme activity of pyruvate dehydrosenase in gerbils" J CBF and Metabol.Vol.15,suppl.1. S197 (1995)

yasuo KATAYAMA：“沙鼠能量代谢方法和丙酮酸脱氢酶线粒体酶活性的缺血耐受现象”J CBF 和 Metabol.Vol.15，suppl.1。

Katayama Y: "Ischemic tolerance phenomenon from an approach of energy metabolism." J.Nippon Med.Sch.61. 134-140 (1994)

Katayama Y：“来自能量代谢途径的缺血耐受现象。”

yasuo KATAYAMA: "lschemic tolerance phenomenon from an approach of energy metabolism and the mitochondrial enzyme activity of pyruvate dehydrogenase in gerbils" J CBF and Metabol.Vol.15,suppl.1.S197 (1995)

yasuo KATAYAMA：“来自能量代谢方法和沙鼠丙酮酸脱氢酶线粒体酶活性的缺血耐受现象”J CBF and Metabol.Vol.15,suppl.1.S197 (1995)

片山 泰朗: "脳代謝よりみた虚血耐性現象" 日医大誌. 61. 134-140 (1994)

Yasuo Katayama：“从脑代谢的角度观察缺血耐受现象”日医大学学报61. 134-140（1994）。