Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Anesthesiology. 2011 May;114(5):1036-47. doi: 10.1097/ALN.0b013e3182104956.
Opioid preconditioning against ischemia reperfusion injury has been well studied in myocardial and neuronal tissues. The objective of this study was to determine whether remifentanil could attenuate hepatic injury and to investigate the mechanisms.
A rat model of hepatic ischemia reperfusion injury and a hepatocyte hypoxia reoxygenation (HR) injury model were used, respectively, in two series of experiments. Remifentanil was administered before ischemia or hypoxia and the experiments were repeated with previous administration of naloxone, L-arginine and N-ω-nitro-L-arginine methyl ester, a nonselective opioid receptor antagonist, a nitric oxide donor, and nitric oxide synthase (NOS) inhibitor, respectively. Serum aminotransferase, cytokines, and hepatic lipid peroxidation were measured. Histopathology examination and apoptotic cell detection were assessed. For the in vitro study, cell viability, intracellular nitric oxide, apoptosis, and NOS expression were evaluated.
Remifentanil and L-arginine pretreatment reduced concentrations of serum aminotransferases and cytokines, decreased the concentrations of hepatic malondialdehyde and myeloperoxidase activity, and increased superoxide dismutase, nitric oxide, and inducible NOS expression in vivo. Decreased histologic damage and apoptosis were also seen in these two groups. These changes were prevented by previous administration of N-ω-nitro-L-arginine methyl ester but not naloxone. There was an increase in inducible NOS protein expression but not endogenous NOS in remifentanil and L-arginine pretreated groups compared with control, naloxone, and N-ω-nitro-L-arginine methyl ester groups.
Pretreatment with remifentanil can attenuate liver injury both in vivo and in vitro. Inducible NOS but not opioid receptors partly mediate this effect by exhausting reactive oxygen species and attenuating the inflammatory response.
阿片类药物预处理可减轻心肌和神经元组织的缺血再灌注损伤，这已经得到了充分的研究。本研究的目的是确定瑞芬太尼是否可以减轻肝损伤，并探讨其机制。
分别采用大鼠肝缺血再灌注损伤模型和肝细胞缺氧复氧（HR）损伤模型进行了两项实验。在缺血或缺氧前给予瑞芬太尼，并分别给予纳洛酮、L-精氨酸和 N-ω-硝基-L-精氨酸甲酯预处理，纳洛酮是一种非选择性阿片受体拮抗剂，L-精氨酸是一氧化氮供体，N-ω-硝基-L-精氨酸甲酯是一氧化氮合酶（NOS）抑制剂。检测血清转氨酶、细胞因子和肝脂质过氧化。评估组织病理学检查和凋亡细胞检测。在体外研究中，评估细胞活力、细胞内一氧化氮、凋亡和 NOS 表达。
瑞芬太尼和 L-精氨酸预处理降低了血清转氨酶和细胞因子的浓度，降低了肝丙二醛和髓过氧化物酶活性的浓度，并增加了超氧化物歧化酶、一氧化氮和诱导型 NOS 的表达。这两组动物的组织学损伤和凋亡也减少。这些变化被 N-ω-硝基-L-精氨酸甲酯预处理所预防，但不能被纳洛酮所预防。与对照组、纳洛酮组和 N-ω-硝基-L-精氨酸甲酯组相比，瑞芬太尼和 L-精氨酸预处理组的诱导型 NOS 蛋白表达增加，但内源性 NOS 表达没有增加。
瑞芬太尼预处理可以减轻体内和体外的肝损伤。诱导型 NOS 但不是阿片受体部分通过耗尽活性氧和减轻炎症反应来介导这种作用。
