一過性脳虚血後の蛋白，RNA合成の変化

CHANGES OF PROTEIN AND RNA SYNTHESIS FOLLOWING ACUTE HINDBRAIN ISCHEMIA

　抄録　脳の蛋白合成およびRNA合成は虚血時のエネルギー代謝の障害に伴い変化すると考えられる。今回，gerbilの後脳虚血モデルを用い蛋白およびRNA合成についてオートラジオグラフィーにより検討した。蛋白合成は指標としてトレーサ—に¹⁴C-valineを用いた。15分間の脳底動脈一時虚血後には，視床内側部，橋および中脳灰白質，下丘，小脳で著明な蛋白合成の低下を認めた。salvage pathwayによるRNA合成はトレーサーに¹⁴C-uridineを，de novo synthesisによるRNA合成はトレーサーに¹⁴C-NaHCO₃と¹⁴C-carbamoylphosphateを用いた。¹⁴C-uridineをトレーサーとするオートラジオグラムでは虚血群で，視床，橋および中脳灰白質でsham controlの1.6-2.4倍にRNA合成が亢進した。¹⁴C-carba-moylphosphateをトレーサーとするオートラジオグラムでは虚血時にも変化を認めなかった。¹⁴C-NaHCO₃をトレーサーとするオートラジオグラムでは蛋白合成と同様虚血部位で合成が著明に低下した。以上より蛋白は虚血部位で著明に合成が障害されるが，salvage pathwayによるRNA合成は虚血後亢進することが示された。一方de novo synthesisによるRNA合成は，NaHCO3, glutamate, ATPよりcarbamoyl—phosphateを合成する段階で障害されるが，成熟砂ネズミではsalvage pathwayによるRNA合成がその大半を占めるためRNA合成全体に与える影響は比較的少なく，RNA合成は全体としては虚血後に増加するものと考えられた。

Protein and RNA synthesis of the brain is affected by focal transient ischemia. Protein syn-thesis is depressed by the depletion of energy metabolism during ischemia, and its recovery following recirculation is slower than restoration of energy metabolism. On the other hand, RNA synthesis is more tolerable to ischemia than pro-tein synthesis. Present study has designed to evaluate changes of protein and RNA synthesis of the brain after ischemia. We used a hindbrain ischemia model of gerbils, and quantitative au-toradiography was applied for estimation of regional protein and RNA synthesis. The model was made by occluding the basilar artery for 15 minutes and recirculating afterwards. ¹⁴C-valine was used as a tracer for protein synthesis. In the ischemic group, proteion synthesis was inhibited extremely in the medial thalamus, inferior colli-culus, gray matter of the pons and midbrain, and cerebellum, RNA synthesis by salvage pathway was evaluated using tracer doses of ¹⁴C-uridine. It increased 1.6-2.4 folds of sham controls in the thalamus, and gray matter of the pons and midbrain. De novo synthesis of RNA was eva-luated using ¹⁴C-carbamoylphosphate and ¹⁴C-NaHCO₃. ¹⁴C-NaHCO₃ antoradiogram showed in-hibition of tracer incorporation into RNA and protein fraction in the ischemic lesions. ¹⁴C-carbamoylphosphate autoradiogram showed no significant change. These results indicate that protein synthesis is inhibited after ischemia but response of RNA synthesis to ischemia is not uniform. De novo synthesis of RNA is inhibited following ischemia, but RNA synthesis by salvage pathway increases in the ischemic lesion. As the most of the RNA synthesis of adult gerbil brain is dependent on the salvage pathway, net RNA synthesis following focal ischemia is considered to increase. This discrepancy of protein and RNA synthesis is unique, and factors other than energy metabolism may play a role for RNA synthesis and its regulation.