七氟醚处理对老龄小鼠脑内神经生长因子表达的影响
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摘要
目的:探讨七氟醚对老年小鼠脑内神经生长因子(NGF)表达的影响。方法:老年C57小鼠吸入七氟醚建立全身麻醉动物模型,利用ELISA检测基底前脑、额叶、颞叶及顶叶NGF的含量,real time RT-PCR检测额叶、颞叶及顶叶NGF mRNA水平,Western Blot检测额叶皮层NGF合成代谢通路中相关蛋白纤溶酶、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子-1(TIMP-1)、丝氨酸或半胱氨酸蛋白水解酶抑制蛋白1(neuroserpin)的表达量。结果:与对照组相比,七氟醚组小鼠基底前脑、额叶、颞叶及顶叶中NGF蛋白含量均显著降低(P <0. 05),但七氟醚组小鼠额叶、颞叶及顶叶中NGF mRNA水平无显著变化。进一步研究发现,七氟醚组小鼠额叶皮层NGF前体蛋白含量增加(P <0. 05),参与NGF翻译后加工的纤溶酶表达显著降低(P <0. 05),neuroserpin表达显著增加(P <0. 05),而参与NGF降解的MMP-9与TIMP-1含量无显著变化。结论:七氟醚可通过抑制NGF翻译后加工过程而降低老年小鼠脑内神经生长因子的含量。
Objective: To explore the effects of sevoflurane on the expression of nerve growth factor( NGF) in the brains of aged mice. Methods: Aged C57 mice were given sevoflurane to induce model of general anesthesia. Protein levels of NGF in the basal forebrain,the frontal cortex,the temporal cortex,and the occipital cortex were determined by ELISA. The levels of NGF mRNA in the frontal cortex,the temporal cortex,and the occipital cortex were measured by real time RT-PCR. The expressions of enzymes involved in NGF metabolism were evaluated by Western Blot,including plasmin,matrix metalloproteinase-9( MMP-9),tissue inhibitor of metalloproteinase-1( TIMP-1),and neuroserpin.Results: Compared with controls,mice treated with sevoflurane showed decreased protein levels of NGF in the basal forebrain,the frontal cortex,the temporal cortex,and the parietal cortex( P < 0. 05). In contrast,the level of NGF mRNA in the frontal cortex,the temporal cortex,and the parietal cortex remained unchanged. In addition,mice treated with sevoflurane exhibited increased levels of pro NGF and neuroserpin and decreased level of plasmin( P < 0. 05). However,compared with controls,the protein levels of MMP-9 and TIMP-1 in the brains of sevoflurane-treated mice remained unchanged. Conclusion: Sevoflurane could decrease the protein level of NGF by inhibiting its post-translational modifications in the brains of aged mice.
Objective: To explore the effects of sevoflurane on the expression of nerve growth factor( NGF) in the brains of aged mice. Methods: Aged C57 mice were given sevoflurane to induce model of general anesthesia. Protein levels of NGF in the basal forebrain,the frontal cortex,the temporal cortex,and the occipital cortex were determined by ELISA. The levels of NGF mRNA in the frontal cortex,the temporal cortex,and the occipital cortex were measured by real time RT-PCR. The expressions of enzymes involved in NGF metabolism were evaluated by Western Blot,including plasmin,matrix metalloproteinase-9( MMP-9),tissue inhibitor of metalloproteinase-1( TIMP-1),and neuroserpin.Results: Compared with controls,mice treated with sevoflurane showed decreased protein levels of NGF in the basal forebrain,the frontal cortex,the temporal cortex,and the parietal cortex( P < 0. 05). In contrast,the level of NGF mRNA in the frontal cortex,the temporal cortex,and the parietal cortex remained unchanged. In addition,mice treated with sevoflurane exhibited increased levels of pro NGF and neuroserpin and decreased level of plasmin( P < 0. 05). However,compared with controls,the protein levels of MMP-9 and TIMP-1 in the brains of sevoflurane-treated mice remained unchanged. Conclusion: Sevoflurane could decrease the protein level of NGF by inhibiting its post-translational modifications in the brains of aged mice.
引文
[1] Zhang Y,Shan GJ,Zhang YX,et al. Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults[J]. Br J Anaesth,2018,121(3):595-604. DOI:10. 1016/j. bja. 2018. 05. 059.
[2]Tian HT,Duan XH,Yang YF,et al. Effects of propofol or sevoflurane anesthesia on the perioperative inflammatory response,pulmonary function and cognitive function in patients receiving lung cancer resection[J]. Eur Rev Med Pharmacol Sci,2017,21(23):5515-5522. DOI:10. 26355/eurrev_201712_13943.
[3]Wu Z,Li X,Zhang Y,et al. Effects of sevoflurane exposure duringmid-pregnancy on learning and memory in offspring rats:Beneficial effects of maternal exercise[J]. Front Cell Neurosci,2018,12:122. DOI:10. 3389/fncel. 2018. 00122.
[4]熊璐,徐文庆,王子高.七氟醚处理对老龄小鼠基底前脑胆碱能系统和认知功能的影响[J].神经解剖学杂志,2016,32(6):757-762. DOI:10. 16557/j. cnki. 1000-7547. 2016. 06.0014.
[5]Bradshaw RA,Mobley W,Rush RA. Nerve growth factor and related substances:A brief history and an introduction to the international NGF meeting series[J]. Int J Mol Sci,2017,18(6):pii:E1143. DOI:10. 3390/ijms18061143.
[6]Indo Y. NGF-dependent neurons and neurobiology of emotions and feelings:Lessons from congenital insensitivity to pain with anhidrosis[J]. Neurosci Biobehav Rev,2018,87:1-16. DOI:10.1016/j. neubiorev. 2018. 01. 013.
[7]Liu TT,Wang H,Wang FJ,et al. Expression of nerve growth factor and brain-derived neurotrophic factor in astrocytomas[J]. Oncol Lett,2018,15(1):533-537. DOI:10. 3892/ol. 2017. 7333.
[8]Iulita MF,Bistue MB,Pentz R,et al. Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer’s disease[J]. Neurobiol Dis,2017,108:307-323. DOI:10. 1016/j. nbd. 2017. 08. 019.
[9] Latina V,Caioli S,Zona C,et al. Impaired NGF/TrkA signaling causes early AD-linked presynaptic dysfunction in cholinergic primary neurons[J]. Front Cell Neurosci,2017,11:68. DOI:10.3389/fncel. 2017. 00068.
[10]Lauzon MA,Faucheux,N. A small peptide derived from BMP-9can increase the effect of bFGF and NGF on SH-SY5Y cells differentiation[J]. Mol Cell Neurosci,2018,88:83-92. DOI:10.1016/j. mcn. 2018. 01. 003.
[11]Chen Y,Pan C,Xuan A,et al. Treatment efficacy of NGF nanoparticles combining neural stem cell transplantation on Alzheimer’s disease model rats[J]. Med Sci Monit,2015,21:3608-3615.DOI:10. 1016/j. mcn. 2018. 01. 003.
[12]Iulita MF,Cuello AC. The NGF metabolic pathway in the CNS and its dysregulation in Down syndrome and Alzheimer’s disease[J].Curr Alzheimer Res,2016,13(1):53-67. DOI:10. 2174/1567205012666150921100030.
[13]Capsoni S,Ruberti F,Di Daniel E,et al. Muscular dystrophy in adult and aged anti-NGF transgenic mice resembles an inclusion body myopathy[J]. J Neurosci Res,2000,59(4):553-560. DOI:10. 1002/(SICI)1097-4547(20000215)59:4 <553::AIDJNR11> 3. 0. CO; 2-4.
[14]Capsoni S,Ugolini G,Comparini A,et al. Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice[J].Proc Natl Acad Sci USA,2000,97(12):6826-6831. DOI:10.1016/S0197-4580(00)82608-1.
[15]Aarao TLS,de Sousa JR,Falcao ASC,et al. Nerve growth factor and pathogenesis of leprosy:Review and update[J]. Front Immunol,2018,9:939. DOI:10. 3389/fimmu. 2018. 00939.
[16]Iulita MF,Cuello AC. The NGF metabolic pathway in the CNS and its dysregulation in Down syndrome and Alzheimer’s disease[J].Curr Alzheimer Res,2016,13(1):53-67. DOI:10. 2174/1567205012666150921100030.
[17] Karayagmurlu A,Ogutlu H,Esin IS,et al. The role of nerve growth factor(NGF)and glial cell line-derived neurotrophic factor(GDNF)in tic disorders[J]. Pak J Med Sci,2018,34(4):844-848. DOI:10. 12669/pjms. 344. 15555.
[18]Fu HD,Wang S,Ge B,et al. Nerve growth factor and substance P may be involved in moist exposed burn ointment-mediated chronic refractory wound healing[J]. Exp Ther Med,2018,16(3):1987-1993. DOI:10. 3892/etm. 2018. 6390.
[19] Leloup N,Chataigner LMP,Janssen BJC. Structural insights into SorCS2-nerve growth factor complex formation[J]. Nat Commun,2018,9(1):2979. DOI:10. 1038/s41467-018-05405-z.
[20]Park JC,Chang IB,Ahn JH,et al. Nerve growth factor stimulates glioblastoma proliferation through Notch1 receptor signaling[J]. J Korean Neurosurg Soc,2018,61(4):441-449. DOI:10. 3340/jkns. 2017. 0219.
[2]Tian HT,Duan XH,Yang YF,et al. Effects of propofol or sevoflurane anesthesia on the perioperative inflammatory response,pulmonary function and cognitive function in patients receiving lung cancer resection[J]. Eur Rev Med Pharmacol Sci,2017,21(23):5515-5522. DOI:10. 26355/eurrev_201712_13943.
[3]Wu Z,Li X,Zhang Y,et al. Effects of sevoflurane exposure duringmid-pregnancy on learning and memory in offspring rats:Beneficial effects of maternal exercise[J]. Front Cell Neurosci,2018,12:122. DOI:10. 3389/fncel. 2018. 00122.
[4]熊璐,徐文庆,王子高.七氟醚处理对老龄小鼠基底前脑胆碱能系统和认知功能的影响[J].神经解剖学杂志,2016,32(6):757-762. DOI:10. 16557/j. cnki. 1000-7547. 2016. 06.0014.
[5]Bradshaw RA,Mobley W,Rush RA. Nerve growth factor and related substances:A brief history and an introduction to the international NGF meeting series[J]. Int J Mol Sci,2017,18(6):pii:E1143. DOI:10. 3390/ijms18061143.
[6]Indo Y. NGF-dependent neurons and neurobiology of emotions and feelings:Lessons from congenital insensitivity to pain with anhidrosis[J]. Neurosci Biobehav Rev,2018,87:1-16. DOI:10.1016/j. neubiorev. 2018. 01. 013.
[7]Liu TT,Wang H,Wang FJ,et al. Expression of nerve growth factor and brain-derived neurotrophic factor in astrocytomas[J]. Oncol Lett,2018,15(1):533-537. DOI:10. 3892/ol. 2017. 7333.
[8]Iulita MF,Bistue MB,Pentz R,et al. Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer’s disease[J]. Neurobiol Dis,2017,108:307-323. DOI:10. 1016/j. nbd. 2017. 08. 019.
[9] Latina V,Caioli S,Zona C,et al. Impaired NGF/TrkA signaling causes early AD-linked presynaptic dysfunction in cholinergic primary neurons[J]. Front Cell Neurosci,2017,11:68. DOI:10.3389/fncel. 2017. 00068.
[10]Lauzon MA,Faucheux,N. A small peptide derived from BMP-9can increase the effect of bFGF and NGF on SH-SY5Y cells differentiation[J]. Mol Cell Neurosci,2018,88:83-92. DOI:10.1016/j. mcn. 2018. 01. 003.
[11]Chen Y,Pan C,Xuan A,et al. Treatment efficacy of NGF nanoparticles combining neural stem cell transplantation on Alzheimer’s disease model rats[J]. Med Sci Monit,2015,21:3608-3615.DOI:10. 1016/j. mcn. 2018. 01. 003.
[12]Iulita MF,Cuello AC. The NGF metabolic pathway in the CNS and its dysregulation in Down syndrome and Alzheimer’s disease[J].Curr Alzheimer Res,2016,13(1):53-67. DOI:10. 2174/1567205012666150921100030.
[13]Capsoni S,Ruberti F,Di Daniel E,et al. Muscular dystrophy in adult and aged anti-NGF transgenic mice resembles an inclusion body myopathy[J]. J Neurosci Res,2000,59(4):553-560. DOI:10. 1002/(SICI)1097-4547(20000215)59:4 <553::AIDJNR11> 3. 0. CO; 2-4.
[14]Capsoni S,Ugolini G,Comparini A,et al. Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice[J].Proc Natl Acad Sci USA,2000,97(12):6826-6831. DOI:10.1016/S0197-4580(00)82608-1.
[15]Aarao TLS,de Sousa JR,Falcao ASC,et al. Nerve growth factor and pathogenesis of leprosy:Review and update[J]. Front Immunol,2018,9:939. DOI:10. 3389/fimmu. 2018. 00939.
[16]Iulita MF,Cuello AC. The NGF metabolic pathway in the CNS and its dysregulation in Down syndrome and Alzheimer’s disease[J].Curr Alzheimer Res,2016,13(1):53-67. DOI:10. 2174/1567205012666150921100030.
[17] Karayagmurlu A,Ogutlu H,Esin IS,et al. The role of nerve growth factor(NGF)and glial cell line-derived neurotrophic factor(GDNF)in tic disorders[J]. Pak J Med Sci,2018,34(4):844-848. DOI:10. 12669/pjms. 344. 15555.
[18]Fu HD,Wang S,Ge B,et al. Nerve growth factor and substance P may be involved in moist exposed burn ointment-mediated chronic refractory wound healing[J]. Exp Ther Med,2018,16(3):1987-1993. DOI:10. 3892/etm. 2018. 6390.
[19] Leloup N,Chataigner LMP,Janssen BJC. Structural insights into SorCS2-nerve growth factor complex formation[J]. Nat Commun,2018,9(1):2979. DOI:10. 1038/s41467-018-05405-z.
[20]Park JC,Chang IB,Ahn JH,et al. Nerve growth factor stimulates glioblastoma proliferation through Notch1 receptor signaling[J]. J Korean Neurosurg Soc,2018,61(4):441-449. DOI:10. 3340/jkns. 2017. 0219.