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

Abstract

Amaç: Serebral İ/R hasarında hücre ölümüne neden olan faktörlerin başında hücre içi kalsiyum konsantrasyonundaki artış gelmektedir. Depo kontrollü Ca²⁺  girişi (Store operated Ca²⁺ entry, SOCE), hücre içine Ca²⁺ girişinden sorumludur ve Orai1, STIM1 ve STIM2 proteinleri aracılığıyla gerçekleşir. 2-Aminoetoksidifenil Borat (2-APB), hücreye depo kontrollü Ca²⁺ girişini engelleyen kimyasal bir ajandır. Bu çalışmada deneysel olarak sıçanlarda oluşturulan serebral İ/R modelinde meydana gelen hasarda 2-APB’nin olası koruyucu etkisi araştırıldı.

Gereç ve Yöntemler: Çalışmada, on sekiz erkek sıçan 3 gruba ayrıldı (n=6). Sham grubunda cerrahi prosedür uygulandı ancak İ/R modeli oluşturulmadı. Sİ/R ve Sİ/R-2APB grubundaki sıçanlara akut serebral İ/R modeli oluşturuldu. Bir saatl sonra reperfüzyon sağlandı. Sİ/R-2APB grubundaki sıçanlara reperfüzyondan 10 dk önce 2-APB uygulandı. Reperfüzyondan 3 saat sonra sıçanlara ötenazi uygulanarak beyinleri çıkarıldı. Sıçan beyin dokularında meydana gelen değişiklikler histokimyasal yöntemlerle, TUNEL metoduyla ve immünohistokimyasal olarak değerlendirildi.

Bulgular: Sİ/R grubunda, sham grubuna kıyasla histolojik yapının bozulduğu, apopitozisin ve Orai1, STIM1 ve STIM2 proteinlerinin ekspresyonunun arttığı belirlendi. 2-APB  uygulanan grupta ise doku hasarının ve apopitotik 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 Ca²⁺  girişini azaltarak apopitozun ve nöronal hasarın azatılmasında etkili olabileceği ortaya konuldu.

Keywords

• 2-Aminoetoksidifenil borat,Serebral iskemi/reperfüzyon,SOCE

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

Abstract

Objective: The store-operated Ca²⁺ entry (SOCE) is responsible for Ca²⁺ entry into the cell and takes place mediated by the Orai1, STIM1, and 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 I/R model. Acute cerebral I/R model was created for rats in the SI/R and SI/R-2APB groups. Reperfusion was realized one-hour later. Ten-minutes before reperfusion, 2-APB was administered to the rats in the SI/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 SI/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.

Keywords

• 2-Aminoethoxydiphenyl borate,Cerebral ischemia / reperfusion,SOCE

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