CAJ | 학술논문

目的探讨激动大麻素受体2对小鼠肝缺血再灌注损伤的预防效果.方法健康雄性C57BL/6J小鼠48只,体重20 ～ 30 g,采用随机数字表法分为4组(n=12):假手术组(S组)、肝缺血再灌注组(I/R组)、大麻素受体2激动剂组(J组)和大麻素受体2激动剂+大麻素受体2拮抗剂组(JS组).采用阻断肝动脉和门静脉30 min,再灌注45 min的方法制备肝缺血再灌注损伤模型.于缺血前60 min,J组腹腔注射大麻素受体2激动剂JWH133 20 mg/kg,JS组腹腔注射JWH 133 20 mg/kg和大麻素受体2拮抗剂SR144528 30 mg/kg.于再灌注45 min时,取肝组织,采用ELISA法检测肝组织TNF-α以及巨噬细胞炎症因子1α(MIP-1α)和MIP-2的含量,采用RT-PCR法检测肝组织TNF-α、MIP-1α、MIP-2和细胞间粘附分子-1(ICAM-1)的mRNA表达,并观察肝组织病理学结果.结果与S组比较,I/R组、J组和JS组肝组织TNF-α、MIP-1α和MIP-2含量升高,TNF-α、MIP-1α、MIP-2和ICAM-1的mRNA表达上调(P＜ 0.05);与I/R组比较,J组肝组织TNF-α、MIP-1α和MIP-2含量降低,TNF-α、MIP-1α、MIP-2和ICAM-1的mRNA表达下调(P＜0.05),JS组上述指标差异无统计学意义(P＞0.05);与J组比较,JS组肝组织TNF-α、MIP-1α和MIP-2含量升高,TNF-α、MIP-1α、MIP-2和ICAM-1的mRNA表达上调(P＜0.05).J组肝组织较I/R组和JS组减轻.结论激动大麻素受体2可对小鼠肝缺血再灌注损伤产生预防效果,机制与抑制肝组织炎性反应有关.
목적 탐토격동대마소수체2대소서간결혈재관주손상적예방효과.방법 건강웅성C57BL/6J소서48지,체중20 ～ 30 g,채용수궤수자표법분위4조(n=12):가수술조(S조)、간결혈재관주조(I/R조)、대마소수체2격동제조(J조)화대마소수체2격동제+대마소수체2길항제조(JS조).채용조단간동맥화문정맥30 min,재관주45 min적방법제비간결혈재관주손상모형.우결혈전60 min,J조복강주사대마소수체2격동제JWH133 20 mg/kg,JS조복강주사JWH 133 20 mg/kg화대마소수체2길항제SR144528 30 mg/kg.우재관주45 min시,취간조직,채용ELISA법검측간조직TNF-α이급거서세포염증인자1α(MIP-1α)화MIP-2적함량,채용RT-PCR법검측간조직TNF-α、MIP-1α、MIP-2화세포간점부분자-1(ICAM-1)적mRNA표체,병관찰간조직병이학결과.결과 여S조비교,I/R조、J조화JS조간조직TNF-α、MIP-1α화MIP-2함량승고,TNF-α、MIP-1α、MIP-2화ICAM-1적mRNA표체상조(P＜ 0.05);여I/R조비교,J조간조직TNF-α、MIP-1α화MIP-2함량강저,TNF-α、MIP-1α、MIP-2화ICAM-1적mRNA표체하조(P＜0.05),JS조상술지표차이무통계학의의(P＞0.05);여J조비교,JS조간조직TNF-α、MIP-1α화MIP-2함량승고,TNF-α、MIP-1α、MIP-2화ICAM-1적mRNA표체상조(P＜0.05).J조간조직교I/R조화JS조감경.결론 격동대마소수체2가대소서간결혈재관주손상산생예방효과,궤제여억제간조직염성반응유관.
Objective To investitate the efficacy of cannabinoid-2 receptor (CB2R) activation in preventing liver ischemia-reperfusion (I/R) injury in mice.Methods Forty-eight male C57BL/6J mice,weighing 20-30 g,were divided into 4 groups (n =12 each):sham operation group (group S),group I/R,CB2R agonist JWH133 group (group J),and CB2R agonist JWH133 + CB2R antagonist SR144528 group (group JS).Liver I/ R was produced by blocking the hepatic artery and portal vein for 30 min followed by 45 min of reperfusion in anesthetized mice.At 60 min before ischemia,JWH133 20 mg/kg was injected intraperitoneally in group J,and JWH133 20 mg/kg and SR144528 30 mg/kg were injected intraperitoneally in group JS.The liver was removed at 45 min of reperfusion for determination of tumor necrosis factor-α (TNF-α),macrophage inflammatory protein-1α (MIP-1α) and MIP-2 contents (using ELISA),and expression of TNF-α,MIP-1α,MIP-2 and intercellular adhesion molecule-1 (ICAM-1) mRNA (by RT-PCR) in the liver tissues and for microscopic examination of the pathological changes.Results Compared with group S,the contents of TNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in J and JS groups.Compared with group I/R,the contents of TNF-α,MIP-1α and MIP-2 were significantly decreased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was down-regulated in J group,and no significant change was found in the parameters mentioned above in JS group.Compared with group J,the contents ofTNF-α,MIP-1α and MIP-2 were significantly increased,and the expression of TNF-α,MIP-1α,MIP-2 and ICAM-1 mRNA was up-regulated in JS group.The pathological changes of liver tissues were significantly attenuated in group J as compared with I/R and JS groups.Conclusion CB2R activation is effective in preventing liver I/R injury in mice and the mechanism is related to inhibitioni of inflammatory responses in liver tissues.