ATP柠檬酸裂解酶在急性胰腺炎胰腺损伤中的作用与机制  

Role of ATP citrate lyase in pancreatic injury during acute pancreatitis and its action mechanism

作　　者：闫昕 丁庆祝 洪育蒲 YAN Xin;DING Qingzhu;HONG Yupu(Department of Hepatopancreatobiliary Surgery,the First Affiliated Hospital,Fujian Medical University,Fuzhou 350005,China;Department of Hepatopancreatobiliary Surgery,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou 350212,China;Fujian Abdominal Surgery Research Institute,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院肝胆胰外科,福建福州350005 [2]福建医科大学附属第一医院滨海院区国家区域医疗中心肝胆胰外科,福建福州350212 [3]福建省腹部外科研究所,福建福州350005

出　　处：《中国普通外科杂志》2024年第12期2030-2037,共8页China Journal of General Surgery

基　　金：福建省卫健委中青年骨干人才培养基金资助项目(2020GAA046);福建省科技厅科技创新联合基金资助项目(2021Y9111)。

摘　　要：背景与目的:ATP柠檬酸裂解酶(Acly)在多种组织中广泛表达,被证实在许多炎症性疾病中发挥着重要作用,但是Acly在急性胰腺炎(AP)胰腺损伤中的作用目前尚不清楚。因此,本研究通过建立小鼠AP模型,观察Acly对AP小鼠胰腺损伤的影响,初步探讨其作用机制。方法:将雄性12只C57BL6/J品系Acly^(cKO)(胰腺Acly基因条件性敲除)小鼠与12只Acly^(wt)(胰腺存在Acly基因)小鼠随机分为AP组(腹腔注射100μg/kg雨蛙素,6次/d,间隔1 h,连续4 d)与对照组(相同方式注射生理盐水),每组Acly^(cKO)小鼠与Acly^(wt)小鼠各6只。在造模完成后24 h收集胰腺组织标本,观察胰腺病理学改变,检测胰腺组织巨噬细胞标志物CD68与中性粒细胞标志物髓过氧化物酶(MPO)表达,以及核因子NF-κB p65、Toll样受体4(TLR4)与促炎因子TNF-α、IL-1β的表达。结果:与对照组比较,AP组小鼠胰腺出现明显胰腺病理改变,且Acly^(cKO)小鼠胰腺病理损伤较Acly~(wt)小鼠更严重,胰腺组织炎症与坏死评分较Acly^(wt)小鼠明显升高(均P<0.05)。AP组中,Acly^(cKO)小鼠胰腺组织CD68、MPO表达均较Acly^(wt)小鼠增强(均P<0.05);Acly^(cKO)小鼠胰腺组织NF-κB p65核阳性比例及TLR4、TNF-α、IL-1β表达均较Acly^(wt)小鼠升高(均P<0.05)。结论:Acly有抗AP胰腺损伤的作用,其机制可能与抑制NF-κB信号通路的活化,从而削弱炎症反应有关。Background and Aims:ATP citrate lyase(Acly)is widely expressed in various tissues and has been shown to play a crucial role in many inflammatory diseases.However,the role of Acly in acute pancreatitis(AP)-induced pancreatic injury remains unclear.This study was conducted to investigate the effect of Acly on pancreatic injury in a mouse AP model and to preliminarily explore its underlying mmeecchhaanniissmm..Methods:Twelve male C57BL6/J Aclycko mice(conditional pancreatic Acly knockout)and twelve Acly^(wt)mice(with intact pancreatic Acly expression)were randomly divided into AP groups(administered caerulein at 100μg/kg intraperitoneally,6 times/d,with 1-hour intervals,for 4 consecutive days)and control groups(administered saline in the same manner),with six Acly^(cKO) mice and six Acly^(wt) mice in each group.Pancreatic tissue samples were collected 24 hours after modeling to observe pathological changes in the pancreas and to measure the expression of the macrophage marker CD68,the neutrophil marker myeloperoxidase(MPO),as well as nuclear factor NF-kB p65,Toll-like receptor 4(TLR4),and pro-inflammatory factors TNF-αand IL-1β.Results:Compared with the control group,the AP group exhibited significant pathological changes in the pancreas.The pathological damage in Aclyeko mice was more severe than in that in Acly^(wt) mice,with significantly higher inflammation and necrosis of pancreatic tissue scores in Aclyeko mice(all P<0.05).In the AP group,the pancreatic expressions of CD68 and MPO were significantly higher in Acly^(cKO) mice than those in Acly^(wt)mice(both P<0.05).Additionally,Acly^(cKO) mice showed increased nuclear positivity for NF-kB p65 and elevated expression ofTLR4,TNF-α,and IL-1βcompared with Acly^(wt)mice(all P<0.05).Conclusion:Acly exerts a protective effect against AP-induced pancreatic injury,possibly by inhibiting the activation of the NF-kB signaling pathway,thereby mitigating the inflammatory response.

关 键 词：胰腺炎 ATP柠檬酸裂解酶 炎症 NF-ΚB 

分 类 号：R657.5[医药卫生—外科学]