Pterin-6-aldehydeによる遅発性神経細胞死阻止に関する研究

蝶呤-6-醛预防神经细胞迟发性死亡的研究

• 批准号: 12770751
• 负责人: 宮田 元
• 金额: $ 1.28万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12770751/
• 关键词: 遅発性神経細胞死; 神経細胞保護; 脳虚血; 抗酸化薬; 免疫組織化学

【目的】Pterin-6-aldehyde(P6A)の遅発性神経細胞死阻止効果と抗酸化薬としての臨床応用への可能性を検討するため,砂ネズミ前脳虚血モデルを用いて組織学的に評価した.【方法】1.ハロセン吸入麻酔下に砂ネズミ(生後8週,オス)の両側総頚動脈を脳動脈瘤クリップで5分間閉塞した.術中,直腸温を37.0±0.2℃に維持したところ,連続して14匹全例が術中死亡または術直後に死亡した.このため,直腸温を30.0±0.2℃に維持し,同様に虚血負荷を加えたところ,28匹中7匹が術後2日以内に死亡し21匹が生存した.この21匹と対照群(手術のみ:5匹,生理食塩水投与群:5匹)について検討した.2.虚血負荷後,30分,3時間,6時間,12時間,24時間,48時間,72時間の時点で各群3匹ずつP6Aを腹腔内投与し,虚血負荷後7日目に経心的に潅流固定した.3.左海馬のパラフィン包埋切片のHE染色と各種免疫染色を行った:HSP32,ユビキチン,MSP23,bax,bcl-2,TUNEL,GFAP,LN-1,RCA-14.右海馬CA1錐体細胞を電顕的に観察した.5.対照群として手術のみで虚血負荷を与えない群5匹と虚血負荷30分後に生理食塩水を腹腔内投与する群5匹を用い,7日後に潅流固定した.【結果】1.対照群ではCA1に虚血性変化や神経細胞死は見られなかった.2.実験群では虚血負荷後P6Aの投与時期にかかわらずCA1に組織学的変化は認められなかった.3.実験群と対照群では免疫組織化学的に明らかな差異は認められなかった.4.実験群と対照群では電顕的にも明らかな差異は認められなかった.【考察】対照群に虚血性変化が見られなかったことは,軽度低体温で5分間の虚血負荷は遅発性神経細胞死の誘発に不十分であるか,あるいは後交通動脈の開存(個体差)により遅発性神経細胞死が免れた可能性が考えられた.現在は手術による死亡率の極めて低いラット高眼圧網膜虚血モデルを用いて,網膜の遅発性神経細胞死に対するP6Aの効果を検討中である.

[Objective] To investigate the possibility of clinical use of Pterin-6-aldehyde(P6A) as an anti-acidification agent for neurocytopathic effect, and to evaluate histologically the role of Pterin-6-aldehyde (P6A) as an anti-acidification agent in neurocytopathic effect. [Methods] 1. The blood vessels of the patients with acute respiratory failure (8 weeks after birth) were divided into two groups: one group was treated with intravenous anesthesia, the other group was treated with intravenous anesthesia. During the operation, rectal temperature was maintained at 37.0±0.2℃, and 14 patients died during the operation. The rectal temperature was maintained at 30.0±0.2℃, while the blood burden was increased. Seven out of 28 died within 2 days after operation, and 21 survived. 21 photos of the group (Surgery:5 pieces, physiological food and water injection and group: 2. After the deficiency of blood load, 30 minutes, 3 times, 6 times, 12 times, 24 times, 48 times, 72 times, each group 3 times, P6A was administered intraperitoneally. 7 days after hypoglycemic stress, the central nervous system was fixed. 3. HE staining of embedded sections of the left hippocampus and various immunostains were performed. HSP32,,MSP23,bax,bcl-2,TUNEL,GFAP,LN-1,RCA-14. The right hippocampus CA1 pyramidal cells were electrically examined. 5. The group of patients with hypoglycemic load after surgery was 5. The group of patients with hypoglycemic load after 30 minutes was 5. The group of patients with physiological diet and intraperitoneal administration was 5. The group of patients with hypoglycemic load was fixed after 7 days. [Results] 1. The expression of P6A in CA1 cells was significantly different from that in CA1 cells. 2. The expression of P6A in CA1 cells was significantly different from that in CA1 cells. 3. The expression of P6A in CA1 cells was significantly different from that in CA1 cells. 4. [Investigation] In contrast to group hypothermia, hypothermia, At present, the mortality rate during surgery is extremely low, the eye pressure is high, the retinal blood deficiency is used, and the effect of retinal neurocyte death on P6A is discussed.