Publication: Nikotinin Sıçan Pankreatit_x000D_
Modelindeki Hafifletici Etkisinde_x000D_
Vagusun Rolünün Araştırılması
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Date
2021-04-01
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Abstract
Nikotinin birçok farklı dokuda anti-inflamatuvar etkilere sahip olduğu ve bu etkileri kolinerjik anti-inflamatuvar yolağı aktive_x000D_
ederek gerçekleştirdiği gösterilmiştir. Çalışmada akut pankreatit modelinde nikotin tedavisinin etkilerini ve bu etkilerin_x000D_
kolinerjik yolla ilişkisini araştırmak amaçlanmıştır. Wistar albino sıçanların pankreas-safra ortak kanalı bağlanırken (PSKB),bir_x000D_
gruba da yalancı-cerrahi (YC) uygulandı. PSKB sıçanlara vagal aferent denervasyon (perivagal kapsaisin; 10mg/ml) veya_x000D_
trunkal vagotomi uygulandı ya da vagusları sağlam bırakıldı. PSKB grupları cerrahi sonrası ikiye ayrılarak 4 gün boyunca_x000D_
intraperitoneal nikotin (1 mg/kg/gün) ya da serum fizyolojik verildi. Dördüncü günde dekapitasyonu takiben, serumda tümör_x000D_
nekroz faktör (TNF)-∝ ve interlökin (IL)-10 ölçümü, akciğer, karaciğer ve pankreas dokularında miyeloperoksidaz aktivitesi_x000D_
(MPO), malondialdehit (MDA), glutatyon (GSH) ölçümleri ve histolojik inceleme yapıldı. TNF-∝ düzeyi PSKB grubunda YC_x000D_
grubuna göre belirgin şekilde daha yüksekken, nikotin tedavisi alanlarda belirgin şekilde daha düşüktü. IL-10 düzeyi ise SF_x000D_
tedavisi almış PSKB grubunda YC grubuna göre daha düşüktü ve nikotin tedavisi ile arttığı gözlendi.YC grubuna göre PSKB_x000D_
grubunun pankreas, karaciğer ve akciğer dokularında mikroskopik hasar, MDA, MPO düzeyleri artarken GSH düzeyleri azaldı._x000D_
Nikotin tedavisi ile karaciğer ve pankreas dokularındaki hasar, MDA, MPO düzeyleri azaldı ve GSH miktarları korundu. Vagal_x000D_
aferent denervasyon ya da trunkal vagotomi yapılması nikotinin bu koruyucu etkilerini değiştirmedi. Sonuçlar, nikotinin_x000D_
pankreatit hasarına karşı koruyucu etkilerini vagal yoldan bağımsız olarak, doğrudan immün hücreler üzerindeki ∝7nAChR_x000D_
aktivasyonu ile nötrofil infiltrasyonunu ve pro-inflamatuvar sitokinleri inhibe ederek gerçekleştirdiğini ortaya koymaktadır._x000D_
_x000D_
Anahtar Kelimeler: pankreatit, nikotin, vagus, inflamasyon, pankreatik kanal bağlama
The anti-inflammatory effects of nicotine on various organs and the involvement of the cholinergic anti-inflammatory_x000D_ pathway activation in these effects were previously shown. The purpose of the study is to evaluate the effects of nicotine_x000D_ treatment on the acute pancreatitis model and to investigate the association of the cholinergic pathway with these effects._x000D_ In Wistar albino rats, the common pancreatic-biliary duct was ligated (PBDL) or sham-operation was performed. In PBDL_x000D_ rats, vagal afferent denervation (perivagal application of capsaicin; 10mg/ml) or truncal vagotomy was applied or the vagi_x000D_ were left intact. Postoperatively, PBDL groups were treated intraperitoneally with either nicotine (1 mg/kg/day) or saline_x000D_ for 4 days. Following decapitation on the 4th day, serum tumor necrosis factor (TNF)-∝ and interleukin (IL)-10 levels and_x000D_ myeloperoxidase activity (MPO), malondialdehyde (MDA) and glutathione (GSH) levels in the pancreas, liver and lung tissues_x000D_ were measured, and histopathological analyses were made. While the TNF-∝ level was significantly higher in the PBDL_x000D_ group than in the sham-operated group, it was significantly lower in the subjects which have taken nicotine treatment. IL-10_x000D_ level was lower in the PBDL group treated with saline than in the sham-operated group and an increase was observed with_x000D_ nicotine treatment.Compared to sham-operated group, microscopic damage scores, MDA, MPO levels in the pancreas, liver_x000D_ and lung tissues of the PBDL group were elevated, while GSH levels were reduced. Nicotine treatment depressed MDA and_x000D_ MPO levels, preserved GSH contents and reduced histological damage in the pancreas and liver. Vagal afferent denervation or_x000D_ truncal vagotomy did not alter these protective effects of nicotine. The results suggest that the protective effects of nicotine on_x000D_ pancreatic inflammation could occur independently of the vagal pathways, but directly by the activation of ∝7-nAChR on the_x000D_ immune cells and by inhibiting neutrophil infiltration and pro-inflammatory cytokine release._x000D_ _x000D_ Keywords: pancreatitis, nicotine, vagus, inflammation, pancreatic duct ligation
The anti-inflammatory effects of nicotine on various organs and the involvement of the cholinergic anti-inflammatory_x000D_ pathway activation in these effects were previously shown. The purpose of the study is to evaluate the effects of nicotine_x000D_ treatment on the acute pancreatitis model and to investigate the association of the cholinergic pathway with these effects._x000D_ In Wistar albino rats, the common pancreatic-biliary duct was ligated (PBDL) or sham-operation was performed. In PBDL_x000D_ rats, vagal afferent denervation (perivagal application of capsaicin; 10mg/ml) or truncal vagotomy was applied or the vagi_x000D_ were left intact. Postoperatively, PBDL groups were treated intraperitoneally with either nicotine (1 mg/kg/day) or saline_x000D_ for 4 days. Following decapitation on the 4th day, serum tumor necrosis factor (TNF)-∝ and interleukin (IL)-10 levels and_x000D_ myeloperoxidase activity (MPO), malondialdehyde (MDA) and glutathione (GSH) levels in the pancreas, liver and lung tissues_x000D_ were measured, and histopathological analyses were made. While the TNF-∝ level was significantly higher in the PBDL_x000D_ group than in the sham-operated group, it was significantly lower in the subjects which have taken nicotine treatment. IL-10_x000D_ level was lower in the PBDL group treated with saline than in the sham-operated group and an increase was observed with_x000D_ nicotine treatment.Compared to sham-operated group, microscopic damage scores, MDA, MPO levels in the pancreas, liver_x000D_ and lung tissues of the PBDL group were elevated, while GSH levels were reduced. Nicotine treatment depressed MDA and_x000D_ MPO levels, preserved GSH contents and reduced histological damage in the pancreas and liver. Vagal afferent denervation or_x000D_ truncal vagotomy did not alter these protective effects of nicotine. The results suggest that the protective effects of nicotine on_x000D_ pancreatic inflammation could occur independently of the vagal pathways, but directly by the activation of ∝7-nAChR on the_x000D_ immune cells and by inhibiting neutrophil infiltration and pro-inflammatory cytokine release._x000D_ _x000D_ Keywords: pancreatitis, nicotine, vagus, inflammation, pancreatic duct ligation