右美托咪定预处理对脓毒症相关性脑病大鼠中枢及外周炎性反应的保护作用

Protective effects of dexmedetomidine preconditioning on central and peripheral inflammatory responses in rats with sepsis-related encephalopathy

目的观察右美托咪啶预处理对脓毒症相关性脑病大鼠中枢及外周炎性反应的保护作用。方法SPF级雌性SD大鼠40只,体质量250-300 g,按随机数字法分4组(n=10):对照组(NC组)、LPS组、DEX干预组(DEX组)以及二甲基亚砜组(DMSO组)。NC组腹腔注射生理盐水1 ml,LPS组腹腔注射10 mg/kg LPS(稀释到1 ml);DEX组在LPS组基础上,注射LPS前30 min腹腔注射100μg/kg右美托咪啶(2%DMSO稀释到1 ml);DMSO组单纯腹腔注射2%DMSO 1 ml,腹腔注射给药6 h后,10%水合氯醛0.4 ml/100 g麻醉成功后抽腹主动脉血和取海马组织。Western blot检测海马组织核转录因子κB(nuclear factor-κB,NF-κB)、IκB、IL-1、TNF-α、iNOS、COX-2表达;ELISA检测外周血TNF-α、IL-1、IL-6、IL-10的浓度;RT-qPCR检测海马组织NF-κB mRNA表达。结果与NC组比较,LPS组外周血清TNF-α、IL-1、IL-6和IL-10表达显著上升(P<0.05);与LPS组比较,DEX组TNF-α、IL-1、IL-6和IL-10表达显著下降(P<0.05)。与NC组比较,LPS组海马组织的TNF-α、IL-1、iNOS、COX-2及NF-κB mRNA表达显著上升(P<0.05),IκB表达显著下降(P<0.05);与LPS组比较,DEX组TNF-α、IL-1、iNOS、COX-2及NF-κB mRNA表达显著下降(P<0.05),IκB表达显著上升(P<0.05)。结论右美托咪啶预处理可改善LPS注射大鼠中枢及外周炎性改变,可能是通过NF-κB/IκB通路调节。

Objective To observe the effect of dexmetomidine pretreatment on central and peripheral inflammation in rats with sepsis-related encephalopathy.Methods Forty female Sprague-Dawley rats of SPF,weighing 250-300 g,were randomly divided into four groups(n=10):control group(NC group),LPS group,DEX group and dimethylsulphoxide group(DMSO group).The rats were intraperitoneally injected with 1 ml of saline in NC group,and LPS(10 mg/kg,diluted to 1 ml)in LPS group.On the basis of LPS group,the rats were intraperitoneally injected with dexmedetomidine(100μg/kg,diluted to 1 ml)30 min before LPS injection in DEX group.In DMSO group,1 ml of 2%DMSO was injected intraperitoneally for 6 h after intraperitoneal injection of 10%chloral hydrate 0.4 ml/100 g,and then the abdominal aortic blood and hippocampus were collected.Western blot was used to detect the expression of NF-κB,IκB,TNF-α,IL-1,iNOS,and COX-2 in hippocampus,ELISA was used to detect the levels of TNF-α,IL-1,IL-6 and IL-10 in peripheral blood.and RT-qPCR was used to detect NF-kappa B expression in hippocampus.Results Compared with NC group,the levels of TNF-α,IL-1,IL-6 and IL-10 in peripheral blood were significantly increased in LPS group(P<0.05).Compared with LPS group,the levels of TNF-α,IL-1,IL-6 and IL-10 were significantly decreased in peripheral blood in DEX group(P<0.05).Compared with NC group,the mRNA expression of TNF-α,IL-1,iNOS,COX-2 and NF-κB was significantly increased in hippocampus in LPS group(P<0.05),while IκB was significantly decreased in LPS group(P<0.05).Compared with LPS group,the mRNA expression of TNF-α,IL-1,iNOS,COX-2 and NF-κB was significantly decreased in DEX group(P<0.05),while IκB expression was significantly increased in DEX group(P<0.05).Conclusion Dexmedetomidine preconditioning can improve the central and peripheral inflammatory changes in septic rats,and may be regulated by the NF-κB/IκB pathway.