Yonezawa Kei, Tolba René H, Wetter Axel, Yamamoto Yuzo, Yamaoka Yoshio, Minor Thomas
Department of Surgery, Division of Surgical Research, University of Bonn, Bonn, Germany.
J Surg Res. 2005 May 1;125(1):16-22. doi: 10.1016/j.jss.2004.11.016.
Carnitine is applied to ameliorate ischemia-reperfusion (I/R) injury of several organs. However, application to hepatic I/R injury is not frequently reported. The aim of this study was to elucidate the effect of exogenous carnitine administration to ameliorate the warm hepatic I/R injury.
Male Wistar rats were divided into two groups, a carnitine group (Car);100 mg/kg of l-carnitine administration and a control group (C); vehicle administration. Thirty minutes after administration, the left hepatic lobes were given 60-min ischemia and then reperfused. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), tumor necrosis factor (TNF)-alpha, and lipoperoxides (LPO) were measured. Hepatic adenosine triphosphate (ATP) concentration was also measured. The hepatic blood flow was estimated using a Laser Doppler. The presence of apoptosis in the livers was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.
In group Car, the blood flow of the left hepatic lobes was better recovered during the reperfusion period than in group C (P < 0.0001). Plasma levels of ALT, AST, GLDH, and TNF-alpha at 1 h after reperfusion were not significantly different between the groups. Although there were no statistical significances, ALT, AST, and TNF-alpha levels in group Car at 24 h after reperfusion tended to be higher than in group C. Plasma LPO levels were not different between the two groups. Also hepatic ATP concentration was not different between the two groups. TUNEL positive liver cells were visible only in group Car at 24 h after reperfusion, but not in the controls.
Although carnitine administration improved the hepatic blood flow during the reperfusion period, we could not demonstrate a protective effect to the hepatic warm I/R injury.
肉碱被用于改善多个器官的缺血再灌注（I/R）损伤。然而，其应用于肝脏I/R损伤的报道并不常见。本研究的目的是阐明外源性给予肉碱对改善肝脏热缺血再灌注损伤的作用。
雄性Wistar大鼠分为两组，肉碱组（Car）；给予100mg/kg的左旋肉碱，对照组（C）；给予溶剂。给药30分钟后，对左肝叶进行60分钟的缺血，然后再灌注。测定血浆丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、谷氨酸脱氢酶（GLDH）、肿瘤坏死因子（TNF）-α和脂质过氧化物（LPO）。还测定了肝脏三磷酸腺苷（ATP）浓度。使用激光多普勒仪估计肝脏血流量。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色评估肝脏中细胞凋亡的存在。
在Car组中，再灌注期间左肝叶的血流比C组恢复得更好（P<0.0001）。再灌注1小时后，两组间血浆ALT、AST、GLDH和TNF-α水平无显著差异。虽然无统计学意义，但再灌注24小时后Car组的ALT、AST和TNF-α水平倾向于高于C组。两组间血浆LPO水平无差异。两组间肝脏ATP浓度也无差异。再灌注24小时后，仅在Car组可见TUNEL阳性肝细胞，而对照组未见。
虽然给予肉碱改善了再灌注期间的肝脏血流，但我们未能证明其对肝脏热缺血再灌注损伤有保护作用。
