CAJ | 학술논문

目的评价不同剂量磷酸肌酸钠预先给药对大鼠肝缺血再灌注损伤的影响.方法健康雄性SD大鼠30只,体重200～250 g,采用随机数字表法分为5组(n=6):假手术组(S组)、缺血再灌注组(I/R组)、不同剂量磷酸肌酸钠预先给药组(P1～3组).采用阻断肝左中动脉及其门静脉90 min恢复灌注的方法制备大鼠肝缺血再灌注模型.P1-3组于缺血前60 min时分别尾静脉注射磷酸肌酸钠50、150和4S0mg/kg.S组和I/R组给予等容量生理盐水.于再灌注4h时采集腹主动脉血样,测定血浆ALT、AST、TNF-α和IL-1β水平.取肝组织,采用ELISA法检测MPO活性,免疫组化法检测细胞间粘附分子(ICAM-1)的表达水平,TUNEL法检测肝细胞凋亡数,电镜下观察病理学结果.结果与S组比较,I/R组和P1～3组肝组织MPO、血浆ALT、AST活性及TNF-α、IL-1β浓度、肝细胞凋亡数升高(P＜0.05)；与I/R组比较,P1～3组上述指标降低(P＜0.05)；P1～3组上述指标依次降低(P＜0.05).结论磷酸肌酸钠预先给药可呈剂量依赖性地减轻大鼠肝缺血再灌注损伤,其机制与抑制炎性反应有关.
목적 평개불동제량린산기산납예선급약대대서간결혈재관주손상적영향.방법 건강웅성SD대서30지,체중200～250 g,채용수궤수자표법분위5조(n=6):가수술조(S조)、결혈재관주조(I/R조)、불동제량린산기산납예선급약조(P1～3조).채용조단간좌중동맥급기문정맥90 min회복관주적방법제비대서간결혈재관주모형.P1-3조우결혈전60 min시분별미정맥주사린산기산납50、150화4S0mg/kg.S조화I/R조급여등용량생리염수.우재관주4h시채집복주동맥혈양,측정혈장ALT、AST、TNF-α화IL-1β수평.취간조직,채용ELISA법검측MPO활성,면역조화법검측세포간점부분자(ICAM-1)적표체수평,TUNEL법검측간세포조망수,전경하관찰병이학결과.결과 여S조비교,I/R조화P1～3조간조직MPO、혈장ALT、AST활성급TNF-α、IL-1β농도、간세포조망수승고(P＜0.05)；여I/R조비교,P1～3조상술지표강저(P＜0.05)；P1～3조상술지표의차강저(P＜0.05).결론 린산기산납예선급약가정제량의뢰성지감경대서간결혈재관주손상,기궤제여억제염성반응유관.
Objective To evaluate the effects of pretreatment with different doses of phosphocreatine on hepatic ischemia-repeffusion (I/R) injury in rats.Methods.Thirty male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 5 groups (n =6 each):sham operation group (group S),hepatic I/R group (group I/R),and pretreatment with different doses of phosphocreatine groups (groups P1-3).Hepatic I/R was induced by 90 min occlusion of the hepatic artery and portal vein entering the middle and left lobes of the liver followed by 4 h reperfusion in anesthetized rats.Phosphocreatine 50,150 and 450 mg/kg were injected via the tail vein at 60 min before ischemia in groups P1-3,respectively.In groups S and I/R,the equal volume of normal saline was given instead.Blood samples were taken from the abdominal aorta at 4 h of reperfusion for determination of plasma alanine aminotransferase (ALT),aspartate aminotransferase (AST),TNF-α and IL-1β concentrations.The rats were then sacrificed and the livers were removed for determination of myeloperoxidase (MPO) activity (by ELISA),intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),and cell apoptosis (by TUNEL) and for microscopic examination (by electron microscopy).Results The MPO activity in liver tissues,plasma ALT and AST activities,TNF-α and IL-1β concentrations and the number of apoptotic cells were significantly higher in groups I/R and P1-3 than in group S,while lower in groups P1-3 than in group I/R (P ＜ 0.05).The parameters mentioned above were decreasedin turn in groups P1-3 (P ＜ 0.05).Conclusion Phosphocreatine pretreatment can attenuate the hepatic I/R injury in rats in a dose-dependent manner and inhibition of the inflammatory responses is involved in the mechanism.