Deneysel akut iskemik inme modelinde terapotik hipoterminin iskemi-reperfüzyon hasarı üzerine etkisi
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Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Kırıkkale Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: İnme, önemli bir sağlık sorunudur ve gelişmiş ülkelerde ölümün üçüncü, sakatlığın ise birinci nedenidir. Akut iskemik inme (Aİİ) tedavisinde amaç kan akımının yeniden sağlanmasıdır. Ancak, kan akımının yeniden sağladığında, beyin dokusunda biriken serbest oksijen radikalleri (SOR) ve inflamatuar sitokinlere bağlı olarak sekonder hasar, bir başka deyişle iskemi/reperfüzyon (I/R) hasarı ortaya çıkar. Target Temperature Management (TTM), I/R hasarı sonucu beyin dokusunda oluşabilecek hasarın azaltılması/düzeltilmesinde kullanılacak tedavi yöntemlerinden biridir. Ancak, hangi ısı derecesinin I/R hasarını önlemede daha etkili olduğuna dair ortak bir bilimsel görüş bulunmamaktadır. Bu çalışmanın amacı, Aİİ'yi takiben I/R hasarı oluşturulan ratlarda hangi ısı derecesinin (normotermi, mild ve moderate hipotermi) nöroprotektif etkisinin daha iyi olduğunu biyokimyasal ve histopatolojik veriler ışığında araştırmaktır. Gereç ve Yöntem: Çalışmaya 28 adet albino-wistar cinsi erkek rat dahil edildi. Ratlar rastgele dört gruba her grupta 7 rat olacak şekilde ayrıldı. Grup-HH: Aİİ'yi takiben I/R hasarı oluşturulan ratlarda hafif hipotermi (32-36oC) uygulanması, Grup-OH: Aİİ'yi takiben I/R hasarı oluşturulan ratlarda orta hipotermi (28-32oC) uygulanması, Grup-NT: Aİİ'yi takiben I/R hasarı oluşturulan ratlarda normotermi (36-38oC) uygulanması ve Grup-K: Kontrol grubu olarak adlandırıldı. Deney bitiminde tüm ratlar sakrifiye edilerek kan ve beyin doku örnekleri alındı. Kan örneklerinden S100B (S100 calcium binding protein-B), NSE (Nöron spesifik enolaz), UCH-L1 (Ubiquitin karboksi-terminal hidrolaz-L1) ve GFAP (Glial fibriler asidik protein) düzeyi çalışıldı. Beyin dokusundaki histopatolojik değişimler (inflamasyon, hemoraji, gliozis ve fibrozis) mikroskobik olarak incelenerek "0=normal, +=hafif, ++=orta ve +++=şiddetli" olarak sınıflandırıldı. Biyokimyasal sonuçların karşılaştırılmasında onewayANOVA ve Independent sample t-testi, Histopatolojik sonuçların karşılaştırılmasında ise Mann-Whitney U-testi ve ki-kare testi kullanıldı. p<0.05 değeri istatistiksel olarak anlamlı kabul edildi. Bulgular: Kontrol grubu gözardı edildiğinde, TTM grupları arasında en düşük NSE düzeyi NT grubunda iken, bunu HH takip ediyordu. NSE düzeyi bakımından gruplar arasında farklılık saptanmadı (p=0.275). İkili karşılaştırmalarda ise yalnızca Grup NT ile Kontrol arasında anlamlı farklılık saptanırken (p=0.040), diğer gruplar arasında farklılık yoktu. vii Gruplar arasında en düşük UCH-L1 düzeyi HH grubunda iken, bunu OH takip ediyordu. UCH-L1 düzeyi bakımından gruplar arasında anlamlı farklılık saptandı (p<0.001). İkili karşılaştırmalarda HH ile Kontrol (p<0.001), OH ile Kontrol (p<0.001) ve NT ile Kontrol (p<0.001) grubu arasında anlamlı farklılık saptanırken, diğer gruplar arasında farklılık yoktu. Gruplar arasında en düşük S100B düzeyi HH grubunda iken, bunu OH takip ediyordu. S100B düzeyi bakımından gruplar arasında anlamlı farklılık saptandı (p=0.034). İkili karşılaştırmalarda ise Grup-HH ile OH (p=0.038) ve HH ile Kontrol (p=0.016) grubu arasında anlamlı farklılık saptanırken, diğer gruplar arasında farklılık yoktu. Gruplar arasında en düşük GFAP düzeyi HH grubunda iken, bunu NT takip ediyordu. Gruplar arasında GFAP düzeyi bakımından anlamlı farklılık saptanmadı (p=0.479). İkili karşılaştırmalarda da gruplar arasında farklılık yoktu. Histopatolojik sonuçlar incelendiğinde gliozis, hemoraji ve fibrozis düzeyi bakımından gruplar arasında farklılık saptanmadı. Kontrol grubu gözardı edildiğinde, TTM grupları arasında, inflamasyon şiddet skorunun en düşük olan grup HH idi. İnflamasyon düzeyi bakımından HH ile Kontrol (p=0.003), HH ile OH (p=0.010) ve OH ile Kontrol (p=0.009) arasında anlamlı farklılık saptandı. Sonuç: Deneysel çalışmamızda en iyi biyokimyasal ve histopatolojik sonuçlar grup HH'de elde edilmiştir. Bu durum, Aİİ sonrası I/R hasarını önlemde ve nöronal dokuları korumada en ideal sıcaklık derecesinin HH olduğu şeklinde yorumlanmıştır. Sonuçlarımızı destekleyecek ileri çalışmalara ihtiyaç vardır. Anahtar kelimeler: Akut iskemik inme, İskemi/Reperfüzyon hasarı, Terapötik hipotermi, NSE, UCH-L1, S100B, GFAP
Introduction and aim: Stroke is a major health problem and is the third leading cause of death and the first cause of disability in developed countries. The aim of treatment for acute ischemic stroke (AIS) is to restore blood flow. However, when blood flow is restored, secondary damage occurs due to free oxygen radicals (FOR) and inflammatory cytokines accumulated in the brain tissue, in other words, Ischemia/Reperfusion (I/R) injury. Target Temperature Management (TTM) is one of the treatment methods to be used in reducing/correcting the damage that may occur in the brain tissue as a result of I/R injury. However, there is no common scientific opinion on which temperature is more effective in preventing I/R injury. The aim of this study is to investigate which temperature (normothermia, mild and moderate hypothermia) has the best neuroprotective effect in rats with I/R injury following AIS in the light of biochemical and histopathological data. Materials and Methods: Twenty-eight albino-wistar male rats were included in the study. The rats were randomly divided into four groups with 7 rats in each group. Group-MiH: Mild hypothermia (32-36oC) was applied to rats that had I/R injury following AIS, Group-MoH: Moderate hypothermia (28-32oC) was applied to rats that had I/R injury following AIS, Group-NT: Normothermia (36-38oC) was applied to rats that had I/R injury following AIS, and Group-K: Control group. At the end of the experiment, all rats were sacrificed and blood and brain tissue samples were taken. S100B (S100 calcium binding protein-B), NSE (Neuron specific enolase), UCH-L1 (Ubiquitin carboxy-terminal hydrolase-L1) and GFAP (Glial fibrillary acidic protein) levels were studied from the blood samples. Histopathological changes in brain tissue (inflammation, hemorrhage, gliosis and fibrosis) were examined microscopically and classified as "0=normal, +=mild, ++=moderate and +++=severe". Oneway-ANOVA and Independent sample t-test were used to compare biochemical results, and Mann-Whitney U-test and chi-square test were used to compare histopathological results. A p<0.05 value was considered statistically significant. Results: When the control group is ignored, the TTM groups the lowest NSE level among the groups was in the NT group, followed by MiH. No difference was found between the groups in terms of NSE level (p=0.275). In binary comparisons, a significant difference was found only between Group NT and Control (p=0.040), while there was no difference between the ix other groups. The lowest UCH-L1 level among the groups was in the MiH group, followed by MoH. A significant difference was found between the groups in terms of UCH-L1 level (p<0.001). In binary comparisons, a significant difference was found between the MiH and Control (p<0.001), MoH and Control (p<0.001) and NT and Control (p<0.001) groups, while there was no difference between the other groups. The lowest S100B level among the groups was in the MiH group, followed by MoH. A significant difference was found between the groups in terms of S100B level (p=0.034). In binary comparisons, there was a significant difference between Group-MiH and MoH (p=0.038) and MiH and Control (p=0.016), while there was no difference between the other groups. The lowest GFAP level among the groups was in the MiH group, followed by NT. There was no significant difference between the groups in terms of GFAP levels (p=0.479). There was no difference between the groups in binay comparisons. When histopathological results were examined, no difference was found between the groups in terms of gliosis, hemorrhage and fibrosis levels. When the control group is ignored, the TTM groups the lowest inflammation severity score was MiH. There was a significant difference between MiH and Control (p=0.003), MiH and MoH (p=0.010) and MoH and Control (p=0.009) in terms of inflammation levels. Conclusion: In our experimental study, the best biochemical and histopathological results were obtained in group MiH. This situation was interpreted as the most ideal temperature degree in preventing I/R injury and protecting neuronal tissues after AIS. Further studies are needed to support our results. Keywords: Acute ischemic stroke, Ischemia/Reperfusion injury, Therapeutic hypothermia, S100B,UCH-L1,NSE,GFAP
Introduction and aim: Stroke is a major health problem and is the third leading cause of death and the first cause of disability in developed countries. The aim of treatment for acute ischemic stroke (AIS) is to restore blood flow. However, when blood flow is restored, secondary damage occurs due to free oxygen radicals (FOR) and inflammatory cytokines accumulated in the brain tissue, in other words, Ischemia/Reperfusion (I/R) injury. Target Temperature Management (TTM) is one of the treatment methods to be used in reducing/correcting the damage that may occur in the brain tissue as a result of I/R injury. However, there is no common scientific opinion on which temperature is more effective in preventing I/R injury. The aim of this study is to investigate which temperature (normothermia, mild and moderate hypothermia) has the best neuroprotective effect in rats with I/R injury following AIS in the light of biochemical and histopathological data. Materials and Methods: Twenty-eight albino-wistar male rats were included in the study. The rats were randomly divided into four groups with 7 rats in each group. Group-MiH: Mild hypothermia (32-36oC) was applied to rats that had I/R injury following AIS, Group-MoH: Moderate hypothermia (28-32oC) was applied to rats that had I/R injury following AIS, Group-NT: Normothermia (36-38oC) was applied to rats that had I/R injury following AIS, and Group-K: Control group. At the end of the experiment, all rats were sacrificed and blood and brain tissue samples were taken. S100B (S100 calcium binding protein-B), NSE (Neuron specific enolase), UCH-L1 (Ubiquitin carboxy-terminal hydrolase-L1) and GFAP (Glial fibrillary acidic protein) levels were studied from the blood samples. Histopathological changes in brain tissue (inflammation, hemorrhage, gliosis and fibrosis) were examined microscopically and classified as "0=normal, +=mild, ++=moderate and +++=severe". Oneway-ANOVA and Independent sample t-test were used to compare biochemical results, and Mann-Whitney U-test and chi-square test were used to compare histopathological results. A p<0.05 value was considered statistically significant. Results: When the control group is ignored, the TTM groups the lowest NSE level among the groups was in the NT group, followed by MiH. No difference was found between the groups in terms of NSE level (p=0.275). In binary comparisons, a significant difference was found only between Group NT and Control (p=0.040), while there was no difference between the ix other groups. The lowest UCH-L1 level among the groups was in the MiH group, followed by MoH. A significant difference was found between the groups in terms of UCH-L1 level (p<0.001). In binary comparisons, a significant difference was found between the MiH and Control (p<0.001), MoH and Control (p<0.001) and NT and Control (p<0.001) groups, while there was no difference between the other groups. The lowest S100B level among the groups was in the MiH group, followed by MoH. A significant difference was found between the groups in terms of S100B level (p=0.034). In binary comparisons, there was a significant difference between Group-MiH and MoH (p=0.038) and MiH and Control (p=0.016), while there was no difference between the other groups. The lowest GFAP level among the groups was in the MiH group, followed by NT. There was no significant difference between the groups in terms of GFAP levels (p=0.479). There was no difference between the groups in binay comparisons. When histopathological results were examined, no difference was found between the groups in terms of gliosis, hemorrhage and fibrosis levels. When the control group is ignored, the TTM groups the lowest inflammation severity score was MiH. There was a significant difference between MiH and Control (p=0.003), MiH and MoH (p=0.010) and MoH and Control (p=0.009) in terms of inflammation levels. Conclusion: In our experimental study, the best biochemical and histopathological results were obtained in group MiH. This situation was interpreted as the most ideal temperature degree in preventing I/R injury and protecting neuronal tissues after AIS. Further studies are needed to support our results. Keywords: Acute ischemic stroke, Ischemia/Reperfusion injury, Therapeutic hypothermia, S100B,UCH-L1,NSE,GFAP
Açıklama
Tıp Fakültesi, Acil Tıp Ana Bilim Dalı
Anahtar Kelimeler
Acil Tıp, Emergency Medicine, Biyokimya
