Investigating TNF-alpha Effects in Ischemic Rat Skin Flaps

Project no. 32872 · Status: Kapanmış (Yayın bekleniyor) · 2025

Summary

<p><strong style="color: black;">AIM:</strong><span style="color: black;">&nbsp;This&nbsp;study&nbsp;aimed&nbsp;to&nbsp;evaluate&nbsp;the&nbsp;effects&nbsp;of&nbsp;ischemia–reperfusion&nbsp;(I/R)&nbsp;injury&nbsp;on&nbsp;TNF-alfa–mediated&nbsp;inflammatory&nbsp;response&nbsp;and&nbsp;angiogenesis&nbsp;in&nbsp;an&nbsp;ischemic&nbsp;rat&nbsp;skin&nbsp;flap&nbsp;model,&nbsp;and&nbsp;to&nbsp;investigate&nbsp;the&nbsp;role&nbsp;of&nbsp;the&nbsp;TNF-alfa&nbsp;inhibitor&nbsp;adalimumab&nbsp;in&nbsp;this&nbsp;process.</span></p><p><strong style="color: black;">MATERIALS&nbsp;AND&nbsp;METHODS:</strong><span style="color: black;">&nbsp;Rats&nbsp;were&nbsp;divided&nbsp;into&nbsp;control&nbsp;and&nbsp;adalimumab-treated&nbsp;groups&nbsp;according&nbsp;to&nbsp;ischemia&nbsp;durations&nbsp;of&nbsp;one&nbsp;hour&nbsp;and&nbsp;four&nbsp;hours.&nbsp;Following&nbsp;reperfusion,&nbsp;flap&nbsp;tissue&nbsp;samples&nbsp;were&nbsp;examined&nbsp;histopathologically.&nbsp;Immunohistochemical&nbsp;staining&nbsp;for&nbsp;TNF-alfa&nbsp;was&nbsp;performed&nbsp;to&nbsp;assess&nbsp;inflammatory&nbsp;response,&nbsp;and&nbsp;VEGF&nbsp;staining&nbsp;was&nbsp;used&nbsp;to&nbsp;evaluate&nbsp;angiogenic&nbsp;activity.&nbsp;The&nbsp;obtained&nbsp;scores&nbsp;were&nbsp;statistically&nbsp;analyzed.</span></p><p><strong style="color: black;">RESULTS:</strong><span style="color: black;">&nbsp;Prolonged&nbsp;ischemia&nbsp;resulted&nbsp;in&nbsp;significantly&nbsp;increased&nbsp;TNF-alfa&nbsp;expression&nbsp;and&nbsp;more&nbsp;severe&nbsp;histopathological&nbsp;tissue&nbsp;damage.&nbsp;The&nbsp;four-hour&nbsp;ischemia&nbsp;control&nbsp;group&nbsp;demonstrated&nbsp;the&nbsp;highest&nbsp;TNF-alfa&nbsp;levels,&nbsp;accompanied&nbsp;by&nbsp;extensive&nbsp;necrosis&nbsp;and&nbsp;marked&nbsp;inflammatory&nbsp;cell&nbsp;infiltration.&nbsp;In&nbsp;adalimumab-treated&nbsp;groups,&nbsp;a&nbsp;reduction&nbsp;in&nbsp;TNF-alfa&nbsp;expression&nbsp;and&nbsp;partial&nbsp;histopathological&nbsp;improvement&nbsp;were&nbsp;observed.&nbsp;This&nbsp;effect&nbsp;was&nbsp;statistically&nbsp;significant&nbsp;in&nbsp;the&nbsp;one-hour&nbsp;ischemia&nbsp;group,&nbsp;whereas&nbsp;in&nbsp;the&nbsp;four-hour&nbsp;ischemia&nbsp;group,&nbsp;inflammatory&nbsp;response&nbsp;could&nbsp;not&nbsp;be&nbsp;completely&nbsp;suppressed.&nbsp;VEGF&nbsp;expression&nbsp;was&nbsp;increased&nbsp;in&nbsp;the&nbsp;early&nbsp;ischemia&nbsp;adalimumab&nbsp;group,&nbsp;while&nbsp;it&nbsp;was&nbsp;decreased&nbsp;and&nbsp;irregular&nbsp;in&nbsp;the&nbsp;prolonged&nbsp;ischemia&nbsp;control&nbsp;group.</span></p><p><strong style="color: black;">CONCLUSION:</strong><span style="color: black;">&nbsp;The&nbsp;findings&nbsp;indicate&nbsp;that&nbsp;ischemia&nbsp;duration&nbsp;is&nbsp;a&nbsp;dominant&nbsp;factor&nbsp;determining&nbsp;TNF-alfa&nbsp;levels&nbsp;and&nbsp;the&nbsp;severity&nbsp;of&nbsp;tissue&nbsp;injury&nbsp;in&nbsp;ischemic&nbsp;skin&nbsp;flaps.&nbsp;Adalimumab&nbsp;may&nbsp;contribute&nbsp;to&nbsp;the&nbsp;preservation&nbsp;of&nbsp;tissue&nbsp;integrity&nbsp;by&nbsp;limiting&nbsp;inflammatory&nbsp;response&nbsp;and&nbsp;supporting&nbsp;angiogenesis,&nbsp;particularly&nbsp;under&nbsp;early&nbsp;ischemic&nbsp;conditions.&nbsp;However,&nbsp;under&nbsp;severe&nbsp;ischemia,&nbsp;TNF-alfa&nbsp;blockade&nbsp;alone&nbsp;may&nbsp;be&nbsp;insufficient,&nbsp;and&nbsp;alternative&nbsp;dosing&nbsp;strategies&nbsp;or&nbsp;combination&nbsp;therapies&nbsp;should&nbsp;be&nbsp;further&nbsp;investigated.</span></p>

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