鼠神经生长因子对巨细胞病毒神经系统感染小鼠海马组织氧化应激及细胞凋亡的影响

Effects of Mouse Nerve Growth Factor on Oxidative Stress and Apoptosis in the Hippocampus of Mice with Cytomegalovirus Infection of the Nervous System

巨细胞病毒(Cytomegalovirus,CMV)感染神经系统可引起神经功能损害,海马组织参与学习、记忆、认知等过程的调控,CMV感染海马组织并引起氧化应激及细胞凋亡激活与神经功能损害的发生密切相关。鼠神经生长因子(mouse nerve growth factor,mNGF)对缺血缺氧、六溴环十二烷等病理因素引起的脑组织氧化应激及细胞凋亡具有改善作用,但mNGF对CMV神经系统感染过程中氧化应激及细胞凋亡的调节作用及机制尚未明确。为研究mNGF对CMV神经系统感染小鼠海马组织氧化应激及细胞凋亡的影响,本研究选择C57BL/6小鼠并随机分为对照组、MCMV组、mNGF组,MCMV组、mNGF组通过腹腔注射病毒液的方式建立MCMV神经系统感染模型,mNGF组从造模后24h开始给予mNGF腹腔注射,连续14d。比较三组小鼠海马组织HE染色、MCMV DNA表达、行为学指标、氧化应激指标含量、凋亡基因及PI3K/PKB通路表达量的差异。结果显示,MCMV组出现了明显的海马组织病理改变且海马组织中MCMV DNA表达水平、bax及cleaved caspase-3表达水平、MDA含量明显高于对照组(P<0.05),bcl-2表达水平、SOD及GSH含量明显低于对照组(P<0.05),逃避潜伏期明显长于对照组,穿越平台次数明显少于对照组(P<0.05);mNGF组海马组织病理改变明显减轻且bax及cleaved caspase-3表达水平、MDA含量明显低于MCMV组(P<0.05),bcl-2表达水平、SOD及GSH含量明显高于MCMV组(P<0.05),逃避潜伏期明显短于MCMV组,穿越平台次数明显多于MCMV组(P<0.05),MCMV DNA表达水平与MCMV组比较无显著性差异(P>0.05)。本研究提示,mNGF对MCMV神经系统感染小鼠的神经功能及病理损害具有改善作用,激活PI3K/PKB通路并抑制氧化应激及细胞凋亡是介导该作用的可能机制。

Cytomegalovirus(CMV)infection of the nervous system can cause neurologic damage.The hippocampus is involved in the regulation of learning,memory and cognition.CMV infection of the hippocampus causes oxidative stress and activates apoptosis,which are closely related to neurologic damage.Mouse nerve growth factor(mNGF)can improve the oxidative stress and apoptosis of brain cells caused by hypoxia,hexabromocyclododecane and other pathologic factors.However,the regulatory effect and mechanism of action of mNGF on oxidative stress and apoptosis in CMV infection of the nervous system are not clear.We wished to study the effect of mNGF on oxidative stress and apoptosis of hippocampal tissue of CMV-infected mice.C57 BL/6 mice were divided randomly into three groups(control,murine CMV(MCMV),mNGF).The MCMV group and mNGF group were injected(i.p.)with MCMV solution to establish the model of CMV infection.The mNGF group was injected(i.p.)with mNGF for 14 days from 24 h after model creation.Differences instaining(hematoxylin and eosin),MCMV DNA copies,oxidative stress,expression of apoptosis genes and PI3 K/PKB pathway among the three groups were compared.There were obvious pathologic changes in the hippocampus in the MCMV group,and expression of Bax,cleaved caspase-3 and the content of malondialdehyde in the hippocampus were significantly higher than those in the control group.Expression of Bcell lymphoma(Bcl)-2 and contents of superoxide dismutase(SOD)and glutathione were significantly lower than those in the control group;the escape latency was significantly longer than that in the control group,and the time for crossing platform was significantly less than that in the control group(P<0.05).The pathologic changes in the hippocampus in the mNGF group were reduced significantly,and expression of Bax,cleaved caspase-3 and malondialdehyde content were significantly lower than those in the MCMV group;expression of Bcl-2,contents of SOD and glutathione were significantly higher than those in the MCMV group,escape latency was significantly shorter than that in the MCMV group,and the crossing-platform time was significantly longer than that in the MCMV group(P<0.05),and there was no significant difference between the MCMV group and mNGF group(P>0.05).Our study suggests that mNGF can improve the neurologic function and pathologic damage in mice infected with MCMV.The possible mechanism of this effect is to activate the PI3 K/PKB pathway and inhibit oxidative stress and apoptosis.