Tuba Demirci, Nuray Bilge, Özlem Özgül Abuç, Nuh Çağrı Karaavcı

2-Aminoetoksidifenil Borat’ın Akut Serebral İskemi-Reperfüzyon Hasarı Üzerindeki Etkisi: Deneysel Bir Çalışma

Amaç Serebral iskemi-reperfüzyon (İ/R) hasarında hücre ölümüne neden olan faktörlerin başında hücre içi kalsiyum konsantrasyonundaki artış gelmektedir. Depo kontrollüCa+2 girişi (Store operated Ca2+ entry, SOCE), hücre içine Ca+2 girişinden sorumludur ve Orai1, stromal etkileşim molekülü 1 (Stromal-interacting molecule1, STIM1) veStromal etkileşim molekülü 2 (Stromal-interacting molecule2, STIM2) proteinleri aracılığıyla gerçekleşir. 2-Aminoetoksidifenil Borat (2-APB), hücreye depo kontrollüCa+2 girişini engelleyen kimyasal bir ajandır. Bu çalışmada deneysel olarak sıçanlarda oluşturulan serebral İ/R modelinde meydana gelen hasarda 2-APB’nin olası koruyucuetkisi araştırıldı.Gereç veYöntemlerÇalışmada, on sekiz erkek sıçan 3 gruba ayrıldı (n=6). Sham grubunda cerrahi prosedür uygulandı ancak serebral İ/R modeli oluşturulmadı. Serebral İ/R ve serebralİ/R-2APB grubundaki sıçanlara İ/R modeli oluşturuldu. Bir saat sonra reperfüzyon sağlandı. Serebral İ/R-2APB grubundaki sıçanlara reperfüzyondan 10 dk önce 2-APBuygulandı. Reperfüzyondan 3 saat sonra sıçanlara ötenazi uygulanarak beyinleri çıkarıldı. Sıçan beyin dokularında meydana gelen değişiklikler histokimyasal yöntemlerle,TUNEL metoduyla ve immünohistokimyasal olarak değerlendirildi.Bulgular Serebral İ/R grubunda, sham grubuna kıyasla histolojik yapının bozulduğu, apoptozun ve Orai1, STIM1 ve STIM2 proteinlerinin ekspresyonunun arttığı belirlendi. 2-APBuygulanan grupta ise doku hasarının ve apoptotik hücrelerin azaldığı, Orai1, STIM1 ve STIM2 ifadesinin belirgin şekilde inhibe edildiği ortaya konuldu.Sonuç Sonuç olarak, serebral İ/R hasarlı dokuda 2-APB’nin hücreye SOCE aracılı Ca+2 girişini azaltarak apoptozun ve nöronal hasarın azatılmasında etkili olabileceği ortayakonuldu.

Effect of 2-Aminoethoxydiphenyl Borate on Acute Cerebral Ischemia-Reperfusion Injury: An Experimental Study

Objective In cerebral ischemia-reperfusion (I/R) injury, an increase in intracellular calcium concentration is the leading factor in cell death. The store-operated Ca2+ entry (SOCE) is responsible for Ca2+ entry into the cell and takes place mediated by the Orai1, Stromal-interacting molecule1 (STIM1), and Stromal-interacting molecule2 (STIM2) proteins. 2-Aminoethoxydiphenyl Borate (2- APB) is a chemical agent that prevents store-operated Ca2+ entry into the cell. In this study, it was investigated the possible protective effect of 2-APB on the occurred injury in the experimental cerebral I/R model in rats. Materials and Methods In the study, eighteen male rats were divided into three groups (n=6). In the Sham group, only surgical procedure was applied without cerebral I/R model. Ischemia-reperfusion model was created for rats in the cerebral I/R and cerebral I/R-2APB groups. Reperfusion was realized one-hour later. Ten-minutes before reperfusion, 2-APB was administered to the rats in the cerebral I/R-2APB group. After three hours of reperfusion, the rats were sacrificed and their brains were removed. The changes that occurred in the brain tissues were investigated by using histochemical methods, the TUNEL, and immunohistochemical staining. Results In the cerebral I/R group, it was determined that the histological structure was impaired and apoptosis and expression of Orai1, STIM1, and STIM2 proteins were increased compared to the sham group. In the 2-APB administrated group, it was revealed that the tissue damage and apoptotic cells were decreased, and Orai1, STIM1, and STIM2 expression were significantly inhibited. Conclusion As a result, it has been demonstrated that 2-APB may be effective in decreasing apoptosis and neuronal damage by reducing SOCE-mediated Ca2+ influx into the cell in cerebral I/R damaged tissue.

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