外源性神经生长因子注射治疗对脑出血大鼠模型神经功能及VEGF和HMGB1表达水平的影响
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摘要
目的探讨神经生长因子(nerve growth factor,NGF)对脑出血(intracerebral hemorrhage,ICH大鼠模型神经功能及血管内皮生长因子(vascular endothelial growth factor,VEGF)和高迁移率族蛋白1(high mobility group box-1 protein,HMGB1)表达水平的影响。方法 SD大鼠(60只)构建脑出血ICH模型,并随机分为对照组、模型组和治疗组,治疗组给予颅内NGF1.0μg血肿内注射1周后检测大鼠神经功能NSS评分;HE染色法观察血肿周围脑组织病理学改变;采用TUNEL法检测神经细胞凋亡;采用Western blot法检测NGF、VEGF和HMGB1蛋白的表达水平。结果与模型组比较,治疗组大鼠NSS评分显著增高,脑组织含水量显著减少(P<0.05);治疗组凋亡细胞数显著减少(P<0.05)。治疗组大鼠脑组织NGF和VEGF蛋白水平显著升高及HMGB1蛋白水平显著降低(P<0.05)。治疗组神经细胞肿胀程度、间隙及细胞核改变均较轻,周围炎症反应和病理学改变减轻。结论外源性神经生长因子有助于改善脑出血大鼠的神经功能损伤,其机制可能通过上调VEGF和下调HMGB1来减轻脑水肿和神经细胞凋亡,从而产生神经保护作用。
Objective To study the effects of exogenous nerve growth factor(NGF)on the neurological function and the expression levels of VEGF and HMGB1 in cerebral hemorrhage(ICH)rats.Methods SD rats(60 rats)were divided into control group,model group and treatment group.The treatment group was given intracranial NGF1.0μg hematoma for 1 week.The neurological NSS scores of rats were detected.The pathological changes of brain tissue around the hematoma were observed by HE staining.The apoptosis of nerve cells was detected by TUNEL method.The expression levels of NGF,VEGF and HMGB1 protein were detected by Western blot.Results Compared with the model group,the NSS scores of the rats in the treatment group were significantly increased,and the water content of the brain tissue was significantly decreased(P<0.05),the number of apoptotic cells in the treatment group was significantly decreased(P<0.05).The expression levels of NGF and VEGF protein in brain tissue of the treatment group were significantly increased,and the expression level of HMGB1 protein was significantly decreased(P<0.05).In the treatment group the degree of swelling,gap and nuclear changes of nerve cells were mild,and the peripheral inflammatory reaction and pathological changes were alleviated.Conclusion Exogenous nerve growth factor could improve the neurological function damage in rats with cerebral hemorrhage.The mechanism might be to reduce the cerebral edema and neuronal apoptosis by up-regulating VEGF and down-regulating HMGB1,thus producing neuroprotective effects.
Objective To study the effects of exogenous nerve growth factor(NGF)on the neurological function and the expression levels of VEGF and HMGB1 in cerebral hemorrhage(ICH)rats.Methods SD rats(60 rats)were divided into control group,model group and treatment group.The treatment group was given intracranial NGF1.0μg hematoma for 1 week.The neurological NSS scores of rats were detected.The pathological changes of brain tissue around the hematoma were observed by HE staining.The apoptosis of nerve cells was detected by TUNEL method.The expression levels of NGF,VEGF and HMGB1 protein were detected by Western blot.Results Compared with the model group,the NSS scores of the rats in the treatment group were significantly increased,and the water content of the brain tissue was significantly decreased(P<0.05),the number of apoptotic cells in the treatment group was significantly decreased(P<0.05).The expression levels of NGF and VEGF protein in brain tissue of the treatment group were significantly increased,and the expression level of HMGB1 protein was significantly decreased(P<0.05).In the treatment group the degree of swelling,gap and nuclear changes of nerve cells were mild,and the peripheral inflammatory reaction and pathological changes were alleviated.Conclusion Exogenous nerve growth factor could improve the neurological function damage in rats with cerebral hemorrhage.The mechanism might be to reduce the cerebral edema and neuronal apoptosis by up-regulating VEGF and down-regulating HMGB1,thus producing neuroprotective effects.
引文
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[13]方顕文,唐贤勇,于大林.乐脉颗粒联合鼠神经生长因子治疗脑梗死的临床研究[J].现代药物与临床,2017,32(8):1421-1424.
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[15]Alsousi A A,Igwe O.Redox-active trace metal-induced release of high mobility group box 1(HMGB1)and inflammatory cytokines in fibroblast-like synovial cells is Toll-like receptor 4(TLR4)dependent[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(11):3847-3858.
[16]Chen Jia,Li Gao-jun.MiR-1284 enhances sensitivity of cervical cancer cells to cisplatin via downregulating HMGB1[J].Biomedicine&Pharmacotherapy,2018,107(107):997-1003.
[17]Zhu C,Chen T,Liu B.Inhibitory effects of miR-25 targeting HMGB1 on macrophage secretion of inflammatory cytokines in sepsis[J].Oncol Lett,2018,16(4):5027-5033.
[2]蒋艳.脑出血康复期患者认知护理干预后血清中MIF和BD-NF含量的影响[J].标记免疫分析与临床,2017,24(9):985-987.
[3]王世金,赵海滨.重组人促红细胞生成素对脑出血患者神经元再生的影响[J].中国全科医学,2011,14(27):3110-3112.
[4]罗章坤,赵睿,李作孝.重组人红细胞生成素对脑出血大鼠血肿周围肿瘤坏死因子-α的影响[J].国际神经病学神经外科学杂志,2016,43(1):34-38.
[5]杨凡慧,曹龄之,黄晓红,等.姜黄素治疗大鼠脑出血后血清IL-6、IL-1β、TNF-α变化的实验研究[J].标记免疫分析与临床,2016,23(9):1033-1037.
[6]陈洁,王萌萌,何妹.预见性护理干预在高血压脑出血急性期患者下肢深静脉血栓形成中的应用[J].血栓与止血学,2018,24(02):331-333.
[7]宋安秀,李学莉.早期活动对脑出血患者术后下肢深静脉血栓形成的预防作用[J].血栓与止血学,2017,23(5):873-874.
[8]Han Y-w,Liu X-j,Zhao Y,et al.Role of oleanolic acid in maintaining BBB integrity by targeting p38MAPK/VEGF/Src signaling pathway in rat model of subarachnoid hemorrhage[J].European Journal of Pharmacology,2018,19(839):12-20.
[9]张鸿,丁天红,张润宁,等.鼠神经生长因子穴位注射治疗顽固性面瘫临床疗效观察[J].四川中医,2017,35(10):190-192.
[10]齐伟平,马伟欢.针刺联合鼠神经生长因子治疗气滞血瘀型突发性耳聋临床观察[J].四川中医,2017,35(11):181-183.
[11]詹传华,汪宏良,李艳.乳腺癌患者血浆神经生长因子和神经生长因子受体检测的临床意义[J].检验医学与临床,2016,13(4):485-486,489.
[12]向勤,吴逊,李泉.血糖波动幅度对2型糖尿病周围神经损害及炎性因子的影响[J].检验医学与临床,2016,13(15):2193-2195.
[13]方顕文,唐贤勇,于大林.乐脉颗粒联合鼠神经生长因子治疗脑梗死的临床研究[J].现代药物与临床,2017,32(8):1421-1424.
[14]Rosso P,Moreno S,Fracassi A,et al.Nerve growth factor and autophagy:effect of nasal anti-NGF-antibodies administration on Ambra1 and Beclin-1 expression in rat brain[J].Growth Factors,2015,33(5/6):401-409.
[15]Alsousi A A,Igwe O.Redox-active trace metal-induced release of high mobility group box 1(HMGB1)and inflammatory cytokines in fibroblast-like synovial cells is Toll-like receptor 4(TLR4)dependent[J].Biochim Biophys Acta Mol Basis Dis,2018,1864(11):3847-3858.
[16]Chen Jia,Li Gao-jun.MiR-1284 enhances sensitivity of cervical cancer cells to cisplatin via downregulating HMGB1[J].Biomedicine&Pharmacotherapy,2018,107(107):997-1003.
[17]Zhu C,Chen T,Liu B.Inhibitory effects of miR-25 targeting HMGB1 on macrophage secretion of inflammatory cytokines in sepsis[J].Oncol Lett,2018,16(4):5027-5033.