普拉克索在减轻小鼠肝缺血再灌注损伤中应用

Pramipexole reduce liver ischemia-reperfusion injury in mice by protecting the mitochondrial function

目的探讨普拉克索(PPX)对小鼠缺血再灌注(I/R)后肝损伤的影响及机制。方法选择健康、雄性C57BL/6小鼠40只,随机分为4组:Sham+DMSO组、Sham+PPX组、I/R+DMSO组、I/R+PPX组,每组各10只。Sham组小鼠仅接受中线开腹、游离肝十二指肠韧带及关腹操作;I/R通过Pringle法诱导肝缺血再灌注模型。DMSO和PPX(1 mg/kg)均在术前30 min腹腔注射。再灌注3、6、24 h后检测血清谷丙转氨酶/谷草转氨酶(ALT/AST)水平,观察肝形态学变化;TUNEL染色了解肝细胞凋亡情况;通过试剂盒检测肝氧化应激指标MDA、HNE、SOD水平;使用Clark氧电极法检测肝线粒体功能指标RCR、ADP/O;检测肝ATP水平。结果与I/R+DMSO组比较,I/R+PPX组小鼠肝功能损伤指标ALT/AST水平显著降低(P<0.01),HE染色显示,I/R+PPX组小鼠肝细胞肿胀、排列紊乱、内皮细胞结构完整性破坏情况有明显改善(P<0.01);而从肝细胞凋亡统计情况可以看出,I/R+PPX组细胞凋亡数量减少(P<0.01);同时,I/R后的氧化应激指标水平较I/R+DMSO组显著减轻(P<0.05);I/R+PPX组肝线粒体功能水平及ATP生成水平较I/R+DMSO组显著提高(P<0.05)。结论 PPX能够保护肝线粒体功能,并进一步减轻肝的I/R损伤。

Objective To investigate the influence of pramipexole（ PPX） in liver ishemia reperfusion（ I / R）. Methods The healthy male mice were ramdonly divided into 4 groups： Sham ＋ DMSO group,Sham ＋ PPX group,I / R ＋ DMSO group,I / R ＋ PPX group. The mice in Sham groups underwent sham procedure,while the mice in I / R groups underwent liver I / R with Pringle＇s methods. DMSO and PPX（ 1 mg / kg） were intraperitoneal injected 30 minutes before operation. Liver function was detected by examining the serum ALT /AST,the morphological changes and apoptosisin in liver tissue were observed 3,6,24 hours after reperfusion,the level of MDA,HNE,SOD were examinded to assess the level of oxidative stress in the liver. RCR,ADP / O and level of ATP were detected to assess the mitochondrial function in the liver. Results Compared with I / R ＋ DMSO group,mice in I / R ＋ PPX group displayed significantly preserved liver funcion as characterized by reduced serum ALT / AST level,less histological damage and apoptosisin. Mechanistic studies revealed that the protection effect of PPX was associated with protection of hepatic mitochondrial function as manifested by oxidative stress index and the level of RCR、ADP / O、ATP. Conclusion Our results indicate that PPX might provide protection for livers against I / R-induced injury by protecting hepatic mitochondrial function.