Gundogdu Zafer, Demirel Ismail, Bayar Mustafa Kemal, Ozkan Zeynep, Bayindir Serpil, Kocyigit Fatma, Hanbeyoglu Onur, Kahraman Mustafa
Middle East J Anaesthesiol. 2016 Oct;23(6):655-663.
Hepatic ischemia-reperfusion (I/R) injury is commonly observed in severe sepsis, hemorrhagic shock, liver transplantation, hepatic resection, and major trauma. Ketamine suppresses the production of cytokines, such as IL-6 and TNF-α, via NF-κB inhibition. We investigated the anti-inflammatory effects of ketamine in liver I/R injury.
Female Wistar-Albino rats (n = 18), weighing 150-200g, were divided into three groups (n = 6 each). Group I underwent reperfusion for 4h following 30 min of ischemia. Group II received 2.5 mg/kg ketamine IM following 30 min of ischemia and 4h of reperfusion and Group III received 10 mg/kg ketamine IM following 30 min of ischemia and 4h of reperfusion. Blood samples were obtained before and after ischemia and reperfusion. MDA, AST, ALT, TNF-α, IL-1β, IL-6, and NO levels were determined. Liver tissue samples were evaluated histologically.
Increased TNF-α, IL-1β, and IL-6 levels were observed in all groups post-ischemia versus pre-ischemia (p <0.05). The TNF-α, IL-1β, and IL-6 levels in Group III increased less than they did in Groups I and II (p <0.05). Higher MDA, NO, AST, and ALT levels were found during the ischemia and reperfusion periods compared with during the pre-ischemia period in all groups (p <0.05). The MDA, NO, AST, and ALT levels of rats that received ketamine increased less than did those of Group I (p <0.05). Significantly less injury was observed in the histopathological analysis of livers of rats administered ketamine (p <0.05).
Ketamine showed a dose-dependent anti-inflammatory effect in I/R injury in the liver when administered after ischemia.
肝缺血再灌注（I/R）损伤常见于严重脓毒症、失血性休克、肝移植、肝切除及重大创伤。氯胺酮通过抑制核因子κB（NF-κB）来抑制细胞因子如白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的产生。我们研究了氯胺酮在肝I/R损伤中的抗炎作用。
体重150 - 200g的雌性Wistar - Albino大鼠（n = 18）分为三组（每组n = 6）。第一组在缺血30分钟后进行4小时的再灌注。第二组在缺血30分钟和再灌注4小时后肌肉注射2.5mg/kg氯胺酮，第三组在缺血30分钟和再灌注4小时后肌肉注射10mg/kg氯胺酮。在缺血和再灌注前后采集血样。测定丙二醛（MDA）、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、TNF-α、白细胞介素-1β（IL-1β）、IL-6和一氧化氮（NO）水平。对肝组织样本进行组织学评估。
与缺血前相比，所有组缺血后TNF-α、IL-1β和IL-6水平均升高（p <0.05）。第三组的TNF-α、IL-1β和IL-6水平升高幅度小于第一组和第二组（p <0.05）。与缺血前相比，所有组在缺血和再灌注期间MDA、NO、AST和ALT水平更高（p <0.05）。接受氯胺酮的大鼠的MDA、NO、AST和ALT水平升高幅度小于第一组（p <0.05）。在给予氯胺酮的大鼠肝脏组织病理学分析中观察到的损伤明显更少（p <0.05）。
缺血后给予氯胺酮在肝I/R损伤中显示出剂量依赖性抗炎作用。
