摘要
目的:探讨右美托咪定(DEX)在大鼠脑缺血再灌注损伤(CIRI)中的作用及其机制。方法:选取雄性SD大鼠72只,随机分为假手术组、模型组、DEX组,各24只。建立CIRI大鼠模型,DEX组在脑缺血1 h时,经尾静脉注射DEX 100μg/kg;其余两组注射等量0.9%氯化钠溶液。评估各组大鼠神经功能缺损情况,测定脑含水量、超氧化物歧化酶(SOD)和丙二醛(MDA)含量。采用TTC染色法检测大鼠脑梗死体积,HE染色观察大鼠脑组织病理学变化。采用TUNEL法检测大鼠海马CA1区神经元凋亡情况。采用Western blot检测大鼠脑组织c-Jun氨基末端激酶(JNK)/核因子-κB(NF-κB)信号通路相关蛋白表达。结果:假手术组大鼠脑组织神经细胞排列整齐,细胞多呈圆形,结构清晰紧密。模型组大鼠神经细胞数量减少,细胞相隔较远且细胞核固缩,排列无序,并可见大量炎症细胞浸润。与模型组比较,DEX组大鼠神经细胞层次较为清楚,细胞数量增加,结构趋于完整,间质水肿状态减轻。与假手术组比较,模型组和DEX组脑含水量、海马CA1区神经细胞凋亡率、脑组织MDA及p-JNK、p65、NF-κB蛋白表达水平明显升高,脑组织SOD水平降低(均P<0.05)。与模型组比较,DEX组Zea Longa评分、脑含水量、脑梗死体积比、海马CA1区神经细胞凋亡率、脑组织MDA及p-JNK、p65、NF-κB蛋白表达水平降低,脑组织SOD水平升高(均P<0.05)。结论:DEX能够恢复CIRI大鼠神经功能,缩小脑梗死灶体积,减轻应激反应,其作用机制可能与JNK/NF-κB信号通路有关。
Objective:To explore the role and mechanism of dexmedetomidine(DEX)in cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:A total of 72 male SD rats were randomly divided into sham operation group,model group and DEX group,with 24 rats each.CIRI rat model was established.DEX group was injected with DEX 100μg/kg through the tail vein at 1 h after cerebral ischemia.The other two groups were injected with 0.9%sodium chloride solution.The neurofunctional impairment of rats in each group was evaluated,and the contents of brain water content,superoxide dismutase(SOD)and malondialdehyde(MDA)were measured.TTC staining was used to detect the infarct volume of rats.HE staining was used to observe the pathological changes of brain tissue.The apoptosis of hippocampal CA1 was detected by TUNEL method.The expression of c-Jun amino-terminal kinase(JNK)/nuclear factor-κB(NF-κB)signaling pathway related proteins in rat brain was detected by Western blot.Results:In the sham operation group,the nerve cells were arranged neatly,and the cells were mostly round with clear and compact structure.In the model group,the number of nerve cells decreased,the cells were far apart,the nuclei were shrunk,the arrangement was disorderly,and a large number of inflammatory cells were infiltrated.Compared with the model group,the level of nerve cells in DEX group was more clear,the number of cells increased,the structure tended to be complete,and the state of interstitial edema was reduced.Compared with the sham operation group,the brain water content,the apoptosis rate of nerve cells in the hippocampal CA1 region,the levels of MDA and p-JNK,p65 and NF-κB proteins in the brain tissue were increased,and the level of SOD in the brain tissue was decreased in the model group and the DEX group(all P<0.05).Compared with the model group,the Zea Longa score,brain water content,cerebral infarct volume ratio,neuronal apoptosis rate in hippocampal CA1 region,and the levels of MDA,p-JNK,p65 and NF-κB proteins in brain tissue were decreased,while the level of SOD was increased in the DEX group(all P<0.05).Conclusion:DEX can promote the recovery of neurofunction in CIRI rats,reduce the volume of cerebral infarction and alleviate stress response,and its mechanism may be related to the JNK/NF-κB signaling pathway.
作者
张博睿
樊龙
姚波
单冰
王建银
赵静
ZHANG Borui;FAN Long;YAO Bo;SHAN Bing;WANG Jianyin;ZHAO Jing(Department of Anesthesiology,Shaanxi Provincial People’s Hospital,Xi’an 710068,China)
出处
《陕西医学杂志》
CAS
2024年第11期1474-1477,1482,共5页
Shaanxi Medical Journal
基金
陕西省自然科学基础研究计划项目(2023-JC-QN-0951)
陕西省重点研发计划项目(2022SF-264)。
