摘要
目的探讨右美托咪定(DEX)通过磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对肝叶切除术后神经认知功能障碍(PNCD)大鼠海马神经元自噬的影响。方法50只大鼠分为对照组、模型组、DEX低、中、高剂量组,每组各10只,模型组七氟醚吸入麻醉下行部分肝叶切除术,DEX低、中、高剂量组分别预先腹腔注射25、50、100μg/kg的DEX,30 min后给予3%七氟醚吸入麻醉,行部分肝叶切除术,对照组仅腹腔注射生理盐水。比较各组术后神经功能缺损程度评分(NSS)及神经认知功能,测定各组海马神经元自噬小体数目及PI3K、Akt、mTOR、自噬标记蛋白(Beclin-1)、微管相关蛋白轻链3(LC3)mRNA及蛋白、pAkt蛋白表达情况。结果DEX各剂量组NSS评分术后3 d、7 d均低于模型组,术后9~11 d逃避潜伏期均短于模型组,其中DEX低剂量组>中剂量组>高剂量组,但仍高于或长于对照组(P<0.05);DEX各剂量组目标象限游泳距离占比均高于模型组,其中DEX低剂量组<中剂量组<高剂量组,但仍低于对照组(P<0.05)。DEX各剂量组自噬小体数目均少于模型组,其中DEX低剂量组>中剂量组>高剂量组,但仍多于对照组(P<0.05)。DEX各剂量组PI3K、mTOR mRNA和蛋白相对表达量、pAkt/Akt均高于模型组,其中DEX低剂量组<中剂量组<高剂量组,但仍低于对照组(P<0.05);DEX各剂量组Beclin-1 mRNA和蛋白、LC3 mRNA相对表达量、LC3-II/LC3-I均低于模型组,其中DEX低剂量组>中剂量组>高剂量组,但仍高于对照组(P<0.05)。结论DEX可能通过激活PI3K/Akt/mTOR信号通路减轻PNCD大鼠神经功能损伤,抑制海马神经元自噬。
Objective To investigate the effect of dexmedetomidine(DEX)on autophagy of hippocampal neurons in rats with post-operative neurocognitive dysfunction(PNCD)after hepatectomy by phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian rapamycin target protein(mTOR)signaling pathway.Methods 50 rats were divided into control group,model group,DEX low,medium and high dose groups.The model group underwent partial hepatectomy under sevoflurane inhalation anesthesia.The DEX low,medium and high dose group were were injected intraperitoneally in advance with 25,50 and 100μg/kg DEX,and 3%sevoflurane inhalation anesthesia was given 30 minutes later,and underwent partial hepatectomy.The control group was only intraperitoneally injected with physiological saline.The neurological severity score(NSS)and neurocognitive function after operation were compared.The number of autophagic bodies and the mRNA and protein expressions of PI3K,Akt,mTOR,autophagic marker protein Beclin-1,microtubule-associated protein light chain 3(LC3),and the expression of pAkt protein in hippocampus of each group were detected.Results The NSS score of DEX each dose group was lower than that of model group at 3 and 7 days after operation,and the escape latency of 9-11 days after operation was shorter than that of model group,among which,DEX low dose group>medium dose group>high dose group,but still higher than or longer than that of control group(P<0.05).The proportion of swimming distance in target quadrant of DEX each dose group was higher than that of model group,among which,DEX low dose group<medium dose group<high dose group,but still lower than that of control group(P<0.05).The number of autophagy bodies of DEX each dose group was less than that in model group,among which,DEX low dose group>medium dose group>high dose group,but still more than that of control group(P<0.05).The relative expressions of PI3K,mTOR mRNA and protein,pAkt/Akt of DEX each dose group were higher than those of model group,among which,DEX low dose group<medium dose
作者
程亮亮
田毅
谭义文
王丹
CHENG Liangliang;TIAN Yi;TAN Yiwen;WANG Dan(Department of Anesthesiology, Haikou Hospital, Xiangya Medical College, Central South University, Haikou 570208, China)
出处
《西部医学》
2021年第6期793-798,803,共7页
Medical Journal of West China
基金
海南省自然科学基金(2016-YNJ-010-010)。
关键词
术后神经认知功能障碍
右美托咪定
神经功能
海马神经元
自噬
Post-operative neurocognitive dysfunction
Dexmedetomidine
Neurological function
Hippocampal neurons
Autophagy
