王彦平;张保朝;温昌明;闻公灵;路海娟;

• 1:南阳市中心医院

摘要(Abstract)：

目的研究红景天苷(Sal)对脑外伤大鼠海马神经元损伤及c-Jun氨基末端激酶3/半胱氨酸天冬氨酸蛋白酶3(JNK3/caspase-3)信号通路的影响。方法取6周龄雄性SD大鼠,参照改良Feeney法制备脑外伤大鼠模型,随机分为模型组、Sal低剂量组[50 mg/(kg·d)灌胃]、Sal中剂量组[100 mg/(kg·d)灌胃]、Sal高剂量组[200 mg/(kg·d)灌胃],每组8只;另设假手术组、正常对照组,每组8只。正常对照组、模型组、假手术组均予以等量生理盐水灌胃,均持续12周。12周末处死,检测各组SD大鼠脑海马组织神经细胞形态变化及凋亡情况、氧化应激指标,包括超氧化物歧化物(SOD)、丙二醛(MAD),免疫印迹(WB)检测海马组织中p-JNK3/JNK3、cleaved-caspase-3蛋白表达水平。结果正常对照组与假手术组大鼠海马神经细胞形态正常,排列整齐,层次丰富,包膜完整。模型组大鼠海马区神经细胞萎缩,排列稀疏,层次减少。Sal低、中、高剂量组大鼠海马区神经细胞形态较模型组依次明显改善。与正常对照组、假手术组比较,模型组大鼠海马神经细胞凋亡、MDA含量、p-JNK3/JNK3、caspase-3蛋白水平显著增加(P<0.05),SOD活性降低(P<0.05);与模型组比较,Sal低、中、高剂量组神经细胞凋亡率、MDA含量、p-JNK3/JNK3、cleaved-caspase-3蛋白水平依次降低(P<0.05),SOD活性依次升高(P<0.05)。结论红景天苷可减轻脑外伤大鼠海马神经元氧化应激损伤,抑制其细胞凋亡,可能与抑制JNK3/caspase-3信号通路有关。

关键词(KeyWords)： 脑外伤;红景天苷;海马;神经元损伤;c-Jun氨基末端激酶3/半胱氨酸天冬氨酸蛋白酶3信号通路;大鼠

Abstract:

Keywords:

基金项目(Foundation): 河南省卫计委科研项目(编号:182102310658)

作者(Authors): 王彦平;张保朝;温昌明;闻公灵;路海娟;

参考文献(References)：

• [1] ADHIKARI K,GUPTA M K,PANT A R,et al.Clinical Patterns and Computed Tomography Findings in Patients with Cranio-Cerebral Trauma in Tertiary Hospital in Eastern Nepal[J].J Nepal Health Res Counc,2019,17(1):56-60.DOI:10.33314/jnhrc.1269.
• [2] ESNAULT P,CARDINALE M,BORET H,et al.Blunt cerebrovascular injuries in severe traumatic brain injury:incidence,risk factors,and evolution[J].J Neurosurg,2017,127(1):16-22.DOI:10.3171/2016.4.JNS152600.
• [3] LIU X,QING WANG,CUI Y,et al.In-depth transcriptomic and proteomic analyses of the hippocampus and cortex in a rat model after cerebral ischemic injury and repair by Shuxuetong (SXT) injection[J].J Ethnopharmacol,2019,249:112362-112392.DOI:10.1016/j.jep.2019.112362.
• [4] LORENZANO S,ROST N S,KHAN M,et al.Oxidative Stress Biomarkers of Brain Damage:Hyperacute Plasma F2-Isoprostane Predicts Infarct Growth in Stroke[J].Stroke,2018,49(3):630-637.DOI:10.1161/STROKEAHA.117.018440.
• [5] ZHONG Z,HAN J,ZHANG J,et al.Pharmacological activities,mechanisms of action,and safety of salidroside in the central nervous system[J].Drug Des Devel Ther,2018,12(1):1479-1489.DOI:10.2147/DDDT.S160776.
• [6] LIU S H,HSIAO Y W,CHONG E,et al.Rhodiola inhibits atrial arrhythmogenesis in a heart failure model[J].J Cardiovasc Electrophysiol,2016,27(9):1093-1101.DOI:10.1111/jce.13026.
• [7] XU Y,JIANG H,SUN C,et al.Antioxidant and hepatoprotective effects of purified Rhodiola rosea polysaccharides[J].Int J Biol Macromol,2018,117:167-178.DOI:10.1016/j.ijbiomac.2018.05.168.
• [8] CONCERTO C,INFORTUNA C,MUSCATELLO M R A,et al.Exploring the effect of adaptogenic Rhodiola Rosea extract on neuroplasticity in humans[J].Complement Ther Med,2018,41:141-146.DOI:10.1016/j.ctim.2018.09.013.
• [9] PEI B,YANG M,QI X,et al.Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway[J].Biochem Biophys Res Commun,2016,478(1):199-205.DOI:10.1016/j.bbrc.2016.07.068.
• [10] WEN X R,FU Y Y,LIU H Z,et al.Neuroprotection of Sevoflurane Against Ischemia/Reperfusion-Induced Brain Injury Through Inhibiting JNK3/Caspase-3 by Enhancing Akt Signaling Pathway[J].Mol Neurobiol,2016,53(3):1661-1671.DOI:10.1007/s12035-015-9111-8.
• [11] 汤莹莹,潘峰,贾俊可.浅低温对小鼠前脑缺血再灌注海马区神经凋亡以及BNIP3表达的影响[J].中国实用神经疾病杂志,2019,22(11):1161-1167.DOI:10.12083/SYSJ.2019.11.157.
• [12] SHATI A A.Salidroside ameliorates diabetic nephropathy in rats by activating renal AMPK/SIRT1 signaling pathway[J].J Food Biochem,2020,44(4):e13158-e13173.DOI:10.1111/jfbc.13158.
• [13] REN M,XU W,XU T.Salidroside represses proliferation,migration and invasion of human lung cancer cells through AKT and MEK/ERK signal pathway[J].Artif Cells Nanomed Biotechnol,2019,47(1):1014-1021.DOI:10.1080/21691401.2019.1584566.
• [14] 冯涛,杨霄鹏.丁苯酞对慢性脑缺血大鼠海马iNOS及MG表达的影响[J].中国实用神经疾病杂志,2018,21(11):1171-1176.DOI:10.12083/SYSJ.2018.11.288.
• [15] ZHANG X,LAI W,YING X,et al.Salidroside Reduces Inflammation and Brain Injury After Permanent Middle Cerebral Artery Occlusion in Rats by Regulating PI3K/PKB/Nrf2/NFκB Signaling Rather than Complement C3 Activity[J].Inflammation,2019,42(5):1830-1842.DOI:10.1007/s10753-019-01045-7.
• [16] LIU H,LIU S,TIAN X,et al.Bexarotene attenuates focal cerebral ischemia-reperfusion injury via the suppression of JNK/Caspase-3 signaling pathway[J].Neurochem Res,2019,44(12):2809-2820.DOI:10.1007/s11064-019-02902-5.
• [17] 孙鸿雁,刘宇.p38MAPK在脑缺血后处理大鼠海马区的表达与意义[J].中国实用神经疾病杂志,2018,21(1):7-11.DOI:10.12083/SYSJ.2018.01.002.
• [18] CHEN Y,ZHENG X,WANG Y,et al.Effect of PI3K/Akt/mTOR signaling pathway on JNK3 in Parkinsonian rats[J].Exp Ther Med,2019,17(3):1771-1775.DOI:10.3892/etm.2018.7120.
• [19] LIU C,ZHANG C W,ZHOU Y,et al.APP upregulation contributes to retinal ganglion cell degeneration via JNK3[J].Cell Death Differ,2018,25(4):663-678.DOI:10.1038/s41418-017-0005-3.
• [20] DE LEMOS L,JUNYENT F,CAMINS A,et al.Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms[J].Mol Neurobiol,2018,55(5):4437-4452.DOI:10.1007/s12035-017-0669-1.
• [21] YU X,ZHONG J,YAN L,et al.Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways[J].Int J Mol Med,2016,38(3):861-868.DOI:10.3892/ijmm.2016.2676.
• [22] ZHANG M,YAN H,LI S,et al.Rosmarinic acid protects rat hippocampal neurons from cerebral ischemia/reperfusion injury via the Akt/JNK3/caspase-3 signaling pathway[J].Brain Res,2017,1657(1):9-15.DOI:10.1016/j.brainres.2016.11.032.