盐酸右美托咪定对脂多糖诱导的库普弗细胞氧化应激和炎性反应的影响

Effect of dexmedetomidine hydrochloride on lipopolysaccharide-induced oxidative stress and inflammatory response in Kupffer cells

目的:探究α2肾上腺能受体激动剂盐酸右美托咪定(Dex)对脂多糖(LPS)诱导的库普弗细胞(KCs)的保护机制。方法:分离和培养KCs,实验分为正常对照组(C组)、LPS损伤组(L组)及LPS+Dex组(L+D组)。L+D组中用Dex预处理24 h,LPS组不予药物预处理。LPS作用24 h建立细胞氧化应激损伤模型,应用MTT比色法检测LPS诱导的KCs存活率;测定细胞上清液中丙二醛(MDA)、白介素(IL)-6、IL-12和肿瘤坏死因子(TNF)-α含量;Western blotting法检测超氧化物歧化酶(SOD)和核因子2相关因子2(NRf2)的蛋白表达水平。结果:L+D组KCs存活率及SOD和NRf2表达水平均显著高于L组,KCs上清液中MDA、IL-6和TNF-α水平显著低于L组(均P<0.05)。结论:Dex可通过上调NRf2表达、减轻氧化应激反应和炎症反应而保护LPS诱导的KCs。

Objective:To explore the protective mechanisms of α2-adrenergic receptor agonist dexmedetomidine hydrochloride(Dex) on Kupffer cells(KCs) injury induced by lipopolysaccharide(LPS).Methods:The KCs were divided into Dex+LPS(L+D) group,LPS(L) group and blank control(C) group.The cells in L+D group were pre-treated with Dex for 24 h.LPS-induced KCs oxidative damage model was established by the administration of LPS for 24 h.MTT colorimetry was used to detect the survival rate of KCs.The levels of MDA,IL-6,IL-12 and TNF-α in the culture medium were assessed.The expressions of SOD and NRf2 were detected by western blotting.Results:The survival rate of KCs and the expressions of SOD and NRf2 in L+D group were higher than those in L group,while the levels of MDA,IL-6 and TNF-α in the culture supernatant were lower(P<0.05).Conclusion:Dex could protect LPS-induced KCs injury though upregulating NRf2 expression and inhibiting oxidative stress and inflammatory response.