盐酸右美托咪定对H_2O_2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 H_2O_2-induced oxidative stress and inflammatory response in Kupffer cells

目的:观察α_2肾上腺能受体激动剂盐酸右美托咪定能否抑制过氧化氢(H_2O_2)诱导的库普弗细胞(Kupffer cells,KCs)氧化应激和炎性反应。方法:分离和培养KCs,分别用盐酸右美托咪定或育亨宾处理24 h后,以H_2O_2作用30 min建立细胞氧化损伤模型,应用MTF比色法检测H_2O_2诱导的损伤细胞的存活率;用相应的试剂盒测定各组细胞上清液中乳酸脱氢酶(lactate dehydrogenase,LDH)、丙二醛(malonaldehyde,MDA)和肿瘤坏死因子-α(TNF-α)释放量。结果:盐酸右美托咪定显著抑制H_2O_2诱导的KCs的损伤,提高细胞的存活率,抑制上清液中LDH,MDA,TNF-α释放,这种作用可以被α_2受体拮抗剂育亨宾完全拮抗,而育亨宾本身对细胞的氧化损伤和炎性反应没有影响。结论:盐酸右美托咪定可以减轻H_2O_2诱导的KCs的氧化应激和炎性反应,其可能是通过α_2肾上腺能受体发挥作用。

Objective：To evaluate whether dexmedetomidine hydrochloride,an α_2-adrenergic receptor agonist,can prevent H_2O_2-induced oxidative stress and inflammatory response in Kupffer cells.Methods：H_2O_2-induced oxidative damage model of Kupffer cell was established.Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h.MTT colorimetry was used to demonstrate the survival rate of Kupffer cells.The levels of lactate dehydrogenase（LDH）,malonaldehyde（MDA） and TNF-a in the culture medium were assessed by corresponding kits.Results：Dexmedetomidine hydrochloride protected Kupffer cells from H_2O_2-induced oxidative damage,showing an increase in the cell survival rate while a decrease in LDH,MDA and TNF-a release in the culture supernatant.Yohimbine,an α_2-adrenergic receptor antagonist,completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells.Yohimbine itself had no effect on H_2O_2-induced oxidative damage and inflammatory response.Conclusion：Dexmedetomidine hydrochloride can prevent H_2O_2-induced oxidative stress and inflammatory response in Kupffer cells through activation of α_2-adrenergic receptors.