右美托咪定通过沉默信息调节因子1/核转录因子信号通路调控脑梗死大鼠海马组织炎症机制研究OACSTPCD
Mechanism of dexmedetomidine regulating hippocampal inflammation in rats with cerebral infarction through SIRT1/NF-κB signaling pathway
目的:探究右美托咪定(Dex)干预对脑梗死大鼠的治疗效果及潜在治疗机制.方法:将60只SPF级SD雄性大鼠随机分为对照组、假手术组、模型组、右美托咪定低剂量组、右美托咪定高剂量组,每组各12只.除对照组、假手术组外,其余各组选用Longa线栓法制备大脑中动脉栓塞(MCAO)模型,假手术组仅剥离肌肉血管.Dex治疗组分别腹腔注射盐酸右美托咪定溶液,其余各组注射等量0.9％氯化钠溶液.比较各组大鼠缺血脑组织的沉默信息调节因子1(SIRT1)、核转录因子(NK-κB)信使RNA(mRNA)和蛋白的相对表达水平及丙二醛(MDA)、超氧化物歧化酶(SOD)水平,同时检测各组大鼠海马区炎性因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平.结果:与对照组大鼠比较,Dex治疗组大鼠SIRT1 mRNA和蛋白水平降低、NF-KBmRNA和蛋白水平升高,经Dex治疗后两组大鼠的SIRT1 mRNA、蛋白水平升高,且Dex高剂量组更高;同时NF-κB mRNA、蛋白水平下降.且Dex高剂量组低于Dex低剂量组;与对照组、假手术组大鼠比较,其余各组大鼠TNF-α、IL-6、MDA水平升高,SOD水平下降,经Dex治疗后两组大鼠的炎性因子和氧化应激水平降低,且Dex高剂量组TNF-α、1L-6、MDA水平低于Dex低剂量组,同时SOD水平升高,且Dex高剂量组更高,差异具有统计学意义(均P＜0.05).结论:右美托咪定可能通过激活SIRT1/NF-kB信号通路,减轻炎性反应,缓解氧化应激,进而发挥脑保护作用.
Objective:To investigate the therapeutic effect of dexmedetomidine(Dex)intervention on cerebral infarction in rats and its potential therapeutic mechanism.Methods:A total of 60 SPF male SD rats were randomly di-vided into control group,sham operation group,model group,low-dose Dex group and high-dose Dex group,with 12 rats in each group.The middle cerebral artery occlusion(MCAO)model was prepared by Longa suture method in the other groups except the control group and the sham operation group.Only the muscle vessels were stripped in the sham operation group.The Dex treatment group was intraperitoneally injected with dexmedetomidine hydrochloride solution,and the other groups were treated with the same amount of 0.9％sodium chloride solution.The mRNA and protein expression levels of silent information regulator 1(SIRT1)and nuclear factor-κb(NK-κB)and the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in ischemic brain tissue were compared among the groups.The levels of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in the hippo-campus of rats in each group were detected,and the levels of inflammatory factors TNF-α and IL-6 in the hippocam-pus of rats in each group were detected.Results:Compared with the control group,the mRNA and protein levels of SIRT1 were decreased and the mRNA and protein levels of NF-KB were increased in the DEX-treated group.After Dex treatment,the mRNA and protein levels of SIRT1 were increased in the two groups,and the high-dose Dex group had a higher expression.At the same time,the NF-κB mRNA and protein levels decreased,and high-dose Dex group was lower than the low-dose Dex group.Compared with the control group and the sham-operation group,the levels of TNF-α,IL-6 and MDA in the other groups were increased,and the level of SOD was decreased.After Dex treatment,the inflammatory factors and oxidative stress levels in the two groups were decreased,and the levels of TNF-α,IL-6 and MDA in the high-dose Dex group were lower than those in the low-dose Dex group,and the level of SOD was increased,and the high-dose Dex group was higher(all P＜0.05).Conclusion:Dexmedetomidine may allevi-ate inflammatory response and oxidative stress by activating SIRT1/NF-kB signaling pathway to exert brain protection.
李显碧;刘尚升;肖兵;廖华;张杨
江油市人民医院麻醉科,四川江油 621700兴文县人民医院麻醉科,四川兴文 644400
临床医学
右美托咪定沉默信息调节因子1/核转录因子肿瘤坏死因子-α白细胞介素-6氧化应激机制
DexmedetomidineSilent information regulator 1/nuclear factorTNF-αIL-6Oxidative stressMechanism
《陕西医学杂志》 2024 (001)
23-27 / 5
四川省医学会科研项目(2021XHNJ36)
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