基于Notch信号转导通路洋川芎内酯Ⅰ对大鼠颅脑损伤后中枢神经再生修复作用  

Regeneration and repair effect of senkyunolideⅠon central nervous system after traumatic brain injury in rats based on Notch signal transduction pathway

作　　者：房正华[1] 马宝林[1] 宋湖平[1] 代景伟[2] 孙晓欧[3] 李海英 FANG Zheng-hua;MA Bao-lin;SONG Hu-ping;DAI Jing-wei;SUN Xiao-ou;LI Hai-ying(Department of Neurosurgery,the First Affiliated Hospital of Xiamen University,Xiamen FUJIAN 361022,China;Department of Anesthesiology,the First Affiliated Hospital of Xiamen University,Xiamen FUJIAN 361022,China;Department of Neurosurgery,the First Affiliated Hospital of Suzhou University,Suzhou JIANGSU 215000,China)

机构地区：[1]厦门大学附属第一医院神经外科,福建厦门361022 [2]厦门大学附属第一医院麻醉科,福建厦门361022 [3]苏州大学附属第一医院神经外科,江苏苏州215000

出　　处：《中国新药与临床杂志》2023年第12期812-817,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金(81771254)。

摘　　要：目的研究洋川芎内酯Ⅰ(SEⅠ)基于Notch信号转导通路对颅脑损伤大鼠中枢神经再生修复功能的影响。方法大鼠随机分为假手术组,模型组,SEⅠ低(SEⅠ-L,36 mg·kg^(-1))、中(SEⅠ-M,72 mg·kg^(-1))、高(SEⅠ-H,144 mg·kg^(-1))剂量组以及SEⅠ(144 mg·kg^(-1))+γ分泌酶抑制剂DAPT(50μg·kg^(-1))组,每组15只。采用改良Feeney自由落体法制备大鼠颅脑损伤模型,于造模成功后24 h内完成第一次给药,连续给药7 d;假手术组仅开颅不致伤。给药结束后对大鼠进行神经功能缺损评分(NSS);采用ELISA法检测外周血清脑源性神经营养因子(BDNF)与神经生长因子(NGF)含量;HE染色观察海马齿状回颗粒下区组织病理变化,q RT-PCR法检测海马组织中Notch1 mRNA的表达情况,Western blot法检测海马组织中Notch1、Hes1、Hes5蛋白表达水平。结果HE染色结果显示,假手术组大鼠海马形态正常,未见损伤;模型组存在明显结构异常,神经元坏死、排列紊乱;SEⅠ3个剂量组随药物剂量升高,神经元排列逐渐整齐有序,坏死情况改善;SEⅠ+DAPT组与SEⅠ-H组相比,神经元改善情况较差。与假手术组比较,模型组大鼠NSS,外周血清BDNF、NGF含量以及海马组织中Notch1 mRNA和Notch1、Hes1、Hes5蛋白表达均显著升高(P<0.05);与模型组比较,SEⅠ3个剂量组NSS均显著降低,BDNF、NGF含量以及Notch1 mRNA和Notch1、Hes1、Hes5蛋白表达均显著升高(P<0.05),且存在剂量依赖性(P<0.05);与SEⅠ-H组比较,SEⅠ+DAPT组NSS显著升高,BDNF、NGF含量以及Notch1 mRNA和Notch1、Hes1、Hes5蛋白表达均显著降低(P<0.05)。结论SEⅠ能够促进颅脑损伤大鼠中枢神经的再生修复,其机制可能与Notch信号转导通路有关。AIM To study the effect of senkyunolideⅠ(SEⅠ)on the regeneration and repair of the central nervous system in rats with traumatic brain injury based on the Notch signal transduction pathway.METHODS Rats were randomly divided into sham operation group,model group,SEⅠ-L(36 mg·kg^(-1))group,SEⅠ-M(72 mg·kg^(-1))group,SEⅠ-H(144 mg·kg^(-1))group,and SEⅠ(144 mg·kg^(-1))+γ-secretase inhibitor DAPT(50μg·kg^(-1))group,15 animals in each group.The rat model of traumatic brain injury was established by the modified Feeney free fall.The first administration was complete within 24 hours after successful modeling,and continuously for 7 days.The sham operation group only underwent craniotomy without causing any injury.After the administration,the neurological severity scores(NSS)of rats were evaluated,the levels of peripheral serum brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)were detected by ELISA,and the histopathological changes in the subgranular region of the dentate gyrus of hippocampus was observed by HE staining.The qRT-PCR method was used to detect the expression of Notch1 mRNA in the hippocampus tissue and Western blot method was used to detect the protein expression levels of Notch1,Hes1,and Hes5 in the hippocampus tissue.RESULTS HE staining showed that the hippocampus of rats in the sham operation group was normal and no damage was found.In the model group,there were obvious structural abnormalities,neuronal necrosis,and disordered arrangement.With the increase of drug dose,the arrangement of neurons in the three dose groups of SEⅠgradually became orderly and the necrosis was improved.Compared with the SEⅠ-H group,the improvement of neurons in the SEⅠ+DAPT group was worse.Compared with the sham operation group,the NSS,the levels of peripheral serum BDNF and NGF,and the expression of Notch1 mRNA and Notch1,Hes1,Hes5protein in the model group were significantly increased(P<0.05).Compared with the model group,the NSS decreased significantly and the levels of BDNF and NGF and

关 键 词：Notch信号转导通路 洋川芎内酯Ⅰ 颅脑损伤 中枢神经系统 神经再生 

分 类 号：R965[医药卫生—药理学] R971[医药卫生—药学]