Mezenter iskemi reperfüzyon hasarı üzerine silimarinin etkisi
The effect of silymarin on intestinal ischemia-reperfusion injury
Yazar: MÜMİN DEMİR
Danışman: PROF. DR. CAFER POLAT
Ondokuz Mayıs Üniversitesi / Tıp Fakültesi / Genel Cerrahi Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2011
Konu: Genel Cerrahi = General Surgery
Dizin: Bağırsaklar = Intestines ; Mezenter = Mesentery ; Mezenterik arterler = Mesenteric arteries ; Mezenterik vasküler tıkanma = Mesenteric vascular occlusion ; Reperfüzyon = Reperfusion ; Reperfüzyon lezyonu = Reperfusion injury ; Silimarin = Silymarin ; Silybum marianum = Silybum marianum ; İskemi = Ischemia

Özet:
AMAÇ: Akut mesenter iskemi acil girişim gerektiren karın hastalıklarının %1-2 sini oluşturmaktadır. Silimarin'in böbrek, karaciğer ve kalp dokusunda iskemi -reperfüzyon hasarını azalttığı rapor edilmiştir. İntestinal sistemde, akut mesenter iskemi hastalığında ve ince barsak transplantasyonu sürecinde iskemi reperfüzyon hasarı yaşanmaktadır. Bu çalışmanın amacı ratlarda silimarinin mezenter iskemi-reperfüzyon hasarı üzerine etkilerini araştırmaktır.MATARYEL VE METOT: Çalışmamızda 5 grupta 10 ar adet yetişkin Wistar Albino rat kullanıldı. Birinci grupta(sham grubu) deneklere sadece laparatomi yapıldı. İkinci grupdaki deneklere (kontrol grubu) süperior mezenterik arter klemplendi. 60 dk iskemi yapıldı ve sonrasında 24 saatlik reperfüzyon sağlandı. Üçüncü grupta 1 saat iskemi, sonrası reperfüzyon sağlandı. Yedi gün, günde bir kez 100 mg /kg oral silimarin verildi. Dördüncü grupta, 7 gün süreyle aynı dozda silimarin verildikden sonra 1 saat mezenter iskemi yapıldı ve 24 saat reperfüzyon sağlandı. Beşinci grupta iskemiden 7 gün önce ve 7 gün sonra aynı dozda silimarin verildi. Tüm deneklerden kan alındı ve iskemi-reperfüzyon hasarı göstergesi olarak oksidatif stres belirteçleri (Hsp 70, süperoksit dismutaz (SOD), malondialdehit (MDA), protein karbonil) ve proinflamatuvar sitokin TNF-? düzeyleri çalışıldı. Terminal ileumdan patolojik inceleme için doku örnekleri alındı.BULGULAR: Serum Hsp 70 düzeyleri kontrol grubuna kıyasla silimarin verilen gruplarda yüksek bulundu (p< 0.05). Kontrol grubuna kıyasla SOD düzeyleri silimarin verilen gruplarda düşük bulundu (p<0.05), ancak Grup V de çok düşük ölçüldü (P< 0.002). Malondialdehit (MDA) ve protein oksidasyon (protein karbonilleri) düzeyleri gruplar arası istatistiksel karşılaştırmada anlamlı bir ilişki bulunamadı. TNF-? düzeyleri kontrol grubuna göre Grup IV de düşük belirlendi (p< 0.05).Sham grubu hariç, kontrol grubunun patolojik lezyon skoru diğer gruplara kıyasla yüksek bulundu. Silimarin verilen gruplarda terminal ileum patolojik lezyon skoru düşük gözlendi, en düşük lezyon kontrole kıyasla Grup V de tesbit edildi (p< 0.01).SONUÇ: Bulgularımız silimarinin, mezenter iskemi-reperfüzyon hasarında, anti enflamatuvar ve kısmen antioksidan etkisinin olduğunu göstermektedir. İskemiden önce ve sonra verildiğinde etkisinin daha iyi olduğu söylenebilir.

Abstract:
Background: Although the mechanism is unknown, Silymarin is shown to have protective effect against kidney, liver, and heart ischemia and reperfusion injury. In this study, the effect of silymarin on intestinal ischemia-reperfusion injury is evaluated.Material and Method: 50 Wistar Albino rats, were divided in to five egual groups. Group I: Sham group, only laparotomy was performed. Group II: Control group, superior mesenteric artery was clamped for 60 minutes and then reperfused for 24 hours. Group III: Superior mesenteric artery was clamped for 60 minutes and then reperfused. Rats were fed with oral 100 mg /kg silymarin for 7 days and were sacrified at 8th day. Group IV: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were sacrified after 24 hour reperfusion. Group V: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were fed with oral 100 mg /kg silymarin for 7 days after ischemia and sacrified at 8th day.Blood were withdrawn during sacrification to study the bood levels of anti-oxidant parameters such as Hsp 70, superoxidet dismutase (SOD), malondealdehyde (MDA), protein carbonyl and proinflammatory cytokines (TNF-?). Terminal ileum was removed for pathological evaluation.Results: Blood Hsp 70 levels were higher in the silymarin given groups than the control group (p< 0.05). SOD levels were lower in the silymarin given groups than the control group (p< 0.05). SOD levels were lowest in Group V (p< 0.002). There was no statisctical difference in malondealdehyde (MDA) and protein oxidation (protein carbonyl) levels among the groups. There was statistically significant difference in TNF-? levels between control group and Grup IV (p< 0.05).Pathological evaluation showed control group had significant morphological changes than the other groups else sham group. Morphological changes were lower in rats received silymarin. This change was prominent in Group V (p< 0.01).Result: Silymarin have anti-inflammatory and anti-oxidant effect on mesenteric ischemia reperfusion damage. This effect is prominent when given before and after ischemia.ABSTRACTBackground: Although the mechanism is unknown, Silymarin is shown to have protective effect against kidney, liver, and heart ischemia and reperfusion injury. In this study, the effect of silymarin on intestinal ischemia-reperfusion injury is evaluated.Material and Method: 50 Wistar Albino rats, were divided in to five egual groups. Group I: Sham group, only laparotomy was performed. Group II: Control group, superior mesenteric artery was clamped for 60 minutes and then reperfused for 24 hours. Group III: Superior mesenteric artery was clamped for 60 minutes and then reperfused. Rats were fed with oral 100 mg /kg silymarin for 7 days and were sacrified at 8th day. Group IV: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were sacrified after 24 hour reperfusion. Group V: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were fed with oral 100 mg /kg silymarin for 7 days after ischemia and sacrified at 8th day.Blood were withdrawn during sacrification to study the bood levels of anti-oxidant parameters such as Hsp 70, superoxidet dismutase (SOD), malondealdehyde (MDA), protein carbonyl and proinflammatory cytokines (TNF-?). Terminal ileum was removed for pathological evaluation.Results: Blood Hsp 70 levels were higher in the silymarin given groups than the control group (p< 0.05). SOD levels were lower in the silymarin given groups than the control group (p< 0.05). SOD levels were lowest in Group V (p< 0.002). There was no statisctical difference in malondealdehyde (MDA) and protein oxidation (protein carbonyl) levels among the groups. There was statistically significant difference in TNF-? levels between control group and Grup IV (p< 0.05).Pathological evaluation showed control group had significant morphological changes than the other groups else sham group. Morphological changes were lower in rats received silymarin. This change was prominent in Group V (p< 0.01).Result: Silymarin have anti-inflammatory and anti-oxidant effect on mesenteric ischemia reperfusion damage. This effect is prominent when given before and after ischemia.ABSTRACTBackground: Although the mechanism is unknown, Silymarin is shown to have protective effect against kidney, liver, and heart ischemia and reperfusion injury. In this study, the effect of silymarin on intestinal ischemia-reperfusion injury is evaluated.Material and Method: 50 Wistar Albino rats, were divided in to five egual groups. Group I: Sham group, only laparotomy was performed. Group II: Control group, superior mesenteric artery was clamped for 60 minutes and then reperfused for 24 hours. Group III: Superior mesenteric artery was clamped for 60 minutes and then reperfused. Rats were fed with oral 100 mg /kg silymarin for 7 days and were sacrified at 8th day. Group IV: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were sacrified after 24 hour reperfusion. Group V: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were fed with oral 100 mg /kg silymarin for 7 days after ischemia and sacrified at 8th day.Blood were withdrawn during sacrification to study the bood levels of anti-oxidant parameters such as Hsp 70, superoxidet dismutase (SOD), malondealdehyde (MDA), protein carbonyl and proinflammatory cytokines (TNF-?). Terminal ileum was removed for pathological evaluation.Results: Blood Hsp 70 levels were higher in the silymarin given groups than the control group (p< 0.05). SOD levels were lower in the silymarin given groups than the control group (p< 0.05). SOD levels were lowest in Group V (p< 0.002). There was no statisctical difference in malondealdehyde (MDA) and protein oxidation (protein carbonyl) levels among the groups. There was statistically significant difference in TNF-? levels between control group and Grup IV (p< 0.05).Pathological evaluation showed control group had significant morphological changes than the other groups else sham group. Morphological changes were lower in rats received silymarin. This change was prominent in Group V (p< 0.01).Result: Silymarin have anti-inflammatory and anti-oxidant effect on mesenteric ischemia reperfusion damage. This effect is prominent when given before and after ischemia.ABSTRACTBackground: Although the mechanism is unknown, Silymarin is shown to have protective effect against kidney, liver, and heart ischemia and reperfusion injury. In this study, the effect of silymarin on intestinal ischemia-reperfusion injury is evaluated.Material and Method: 50 Wistar Albino rats, were divided in to five egual groups. Group I: Sham group, only laparotomy was performed. Group II: Control group, superior mesenteric artery was clamped for 60 minutes and then reperfused for 24 hours. Group III: Superior mesenteric artery was clamped for 60 minutes and then reperfused. Rats were fed with oral 100 mg /kg silymarin for 7 days and were sacrified at 8th day. Group IV: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were sacrified after 24 hour reperfusion. Group V: Rats were fed with oral 100 mg /kg silymarin for 7 days and then superior mesenteric artery was clamped for 60 minutes. Rats were fed with oral 100 mg /kg silymarin for 7 days after ischemia and sacrified at 8th day.Blood were withdrawn during sacrification to study the bood levels of anti-oxidant parameters such as Hsp 70, superoxidet dismutase (SOD), malondealdehyde (MDA), protein carbonyl and proinflammatory cytokines (TNF-?). Terminal ileum was removed for pathological evaluation.Results: Blood Hsp 70 levels were higher in the silymarin given groups than the control group (p< 0.05). SOD levels were lower in the silymarin given groups than the control group (p< 0.05). SOD levels were lowest in Group V (p< 0.002). There was no statisctical difference in malondealdehyde (MDA) and protein oxidation (protein carbonyl) levels among the groups. There was statistically significant difference in TNF-? levels between control group and Grup IV (p< 0.05).Pathological evaluation showed control group had significant morphological changes than the other groups else sham group. Morphological changes were lower in rats received silymarin. This change was prominent in Group V (p< 0.01).Result: Silymarin have anti-inflammatory and anti-oxidant effect on mesenteric ischemia reperfusion damage. This effect is prominent when given before and after ischemia.