丙泊酚抑制体外循环模型大鼠神经细胞凋亡机制研究OA
Study on the Mechanism of Propofol Inhibiting Neuronal Apoptosis in the Rat Model of Cardiopulmonary Bypass
目的 探讨丙泊酚对体外循环(CPB)模型大鼠海马神经细胞凋亡的影响.方法 以插管法复制 CPB 大鼠模型.将 60 只大鼠随机分为对照组(等体积生理盐水)、模型组(等体积生理盐水)、右美托咪定组(5µg/kg)及丙泊酚低、中、高剂量组(10,20,40 mg/kg),各 10 只.采用改良神经功能评分(mNSS)法评估大鼠神经功能损伤程度;采用 Morris 水迷宫实验(MWM)评估大鼠学习记忆能力;采用苏木精-伊红(HE)和尼氏(Nissl)染色分析大鼠海马组织神经病理形态变化,并进行评分;采用末端脱氧核苷酸转移酶介导的dUTP 缺口末端标记(TUNEL)法检测大鼠海马组织细胞凋亡情况,并计算凋亡率;检测大鼠海马组织匀浆中白细胞介素(IL)6、肿瘤坏死因子-α(TNF-α)、IL-1β、丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)水平;采用 Western blot 法检测大鼠海马组织中磷酸化细胞外调节蛋白激酶(p-ERK1/2)、过氧化物酶体增殖物激活受体 γ(PPARγ)蛋白表达水平.结果 模型组大鼠海马组织排列紊乱、被大量炎性细胞浸润,且大量 Nissl 小体丢失.与模型组比较,右美托咪定及丙泊酚中、高剂量组大鼠海马组织排列逐渐整齐、炎性细胞浸润程度逐渐降低,Nissl 小体逐渐增多,逃避潜伏期显著缩短,mNSS 评分、病理评分、细胞凋亡率、IL-6、TNF-α、IL-1β、MDA 及 p-ERK1/2 水平均显著降低(P<0.05);穿台次数显著增加,SOD、GSH 及 PPARγ 水平均显著升高(P<0.05).结论 丙泊酚能通过抑制 ERK1/2/PPARγ 信号通路减轻 CPB 模型大鼠海马神经细胞的凋亡.
Objective To investigate the effect of propofol on hippocampal neuronal apoptosis in the rat model of cardiopulmonary bypass(CPB).Methods A rat model of CPB was established by intubation.A total of 60 rats were randomly divided into control group(equal volume of normal saline),model group(equal volume of normal saline),dexmedetomidine group(5 µg/kg),and low-,medium-,and high-dose propofol groups(10,20,40 mg/kg),with 10 rats in each group.Neurological impairment was assessed using the modified neurological severity score(mNSS).Learning and memory abilities were evaluated using the Morris water maze(MWM)test.Neuropathological morphological changes in the hippocampus were analyzed by hematoxylin-eosin(HE)and Nissl staining,followed by pathological scoring.Apoptosis in hippocampal tissue was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assay,and the apoptotic rate was calculated.Levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),IL-1β,malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)in hippocampal homogenates were detected.Protein expression levels of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and peroxisome proliferator-activated receptor γ(PPARγ)in hippocampal tissue were detected by Western blot.Results In the model group,the hippocampal tissue showed disorganized arrangement,extensive inflammatory cell infiltration,and significant loss of Nissl bodies.Compared with those in the model group,the dexmedetomidine group and the medium-and high-dose propofol groups exhibited progressively more orderly hippocampal tissue arrangement,reduced inflammatory cell infiltration,increased Nissl bodies,escape latency were significantly shortened,and mNSS score,pathological score,apoptosis rate,levels of IL-6,TNF-α,IL-1β,MDA,and p-ERK1/2 were significantly decreased(P<0.05).The number of platform crossings,levels of SOD,GSH,and PPARγ were significantly increased(P<0.05).Conclusion Propofol can reduce hippocampal neuronal apoptosis in rat model of CPB by inhibiting the ERK1/2/PPARγ signaling pathway.
王飞;刘硕;王存斌
天津市北辰医院,天津 300400首都医科大学附属北京潞河医院,北京 101199天津市北辰医院,天津 300400
医药卫生
丙泊酚体外循环神经细胞凋亡ERK1/2/PPARγ信号通路
propofolcardiopulmonary bypassneuronal apoptosisERK1/2/PPARγ signaling pathway
《中国药业》 2026 (8)
64-70,7
天津市卫生健康科技项目[TJWJ2022MS752].
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