地塞米松联合阿昔洛韦对单纯疱疹病毒性脑炎小鼠预后及IL-2表达的影响

Effect of dexamethasone and acyclovir on prognosis and expression of IL-2 in mice with herpes simplex virus encephalitis

目的探讨地塞米松联合阿昔洛韦治疗单纯疱疹病毒性脑炎小鼠的预后,及其对IL-2表达的影响。方法颅内接种单纯疱疹病毒1型建立单纯疱疹病毒性脑炎小鼠模型,并设正常对照组、病毒感染组、阿昔洛韦组和地塞米松联合阿昔洛韦组。通过神经症状评分观察单纯疱疹病毒性脑炎小鼠的发病情况,并对其神经损伤症状进行评估;详细记录小鼠死亡的时间及数量,待病情不再发展时对各治疗组小鼠行生存率分析;应用免疫组化法测定小鼠脑组织中IL-2的表达并比较;采用Spearman相关分析描述神经症状评分与IL-2表达的相关性。结果病毒感染组小鼠神经症状评分最高、生存率最低,而地塞米松联合阿昔洛韦组神经症状评分最低、生存率最高,阿昔洛韦组则介于两者之间,四组间差异有统计学意义(P<0.05)。病毒感染组小鼠脑组织中IL-2的表达较正常对照组明显上调,阿昔洛韦组有所下降,地塞米松联合阿昔洛韦组明显下降,但仍高于对照组,四组间差异有统计学意义(P<0.05)。小鼠感染病毒第6天的神经症状评分与IL-2表达呈显著正相关(r=0.639,P=0.000)。结论阿昔洛韦联合糖皮质激素治疗小鼠单纯疱疹病毒性脑炎,较单纯抗病毒治疗生存率显著提高,临床症状减轻;单纯疱疹病毒性脑炎小鼠神经损伤程度与脑组织IL-2表达呈正相关。

Objective To study the treatment using dexamethasone and aeyclovir in mice with herpes simplex virus encephalitis （HSE） and its effect on expression oflL-2. Methods Mice model of riSE were induced by intraeranial inoculation of herpes simplex virus type 1 and were randomly assigned into control group, HSV-1 infection group, acyclovir treated group, and dexamethasone and acyclovir treated group. The mice were observed and scores of neurological injury were assessed. The death time and death quantity were also recorded. When the mice condition became stable, the survival rates were analyzed, and the expressions of IL-2 in mice brain tissues measured by immunohistochemistry were compared. The Spearman correlation was calculated between neurological injury score and expression of IL-2. Results In HSV-1 infection group, the neurological injury score was the highest and the survival rate was lowest （P〈0.05）. On the contrary, the lowest neurological injury score and highest survival rate were observed in dexamethasone treated group （P〈0.05）. For acyclovir group, the neurological injury score and survival rate fell between the above the two groups. The significant differences were presented among these 4 groups （P〈0.05）. The expression of IL-2 markedly increased in HSV-1 infection group, while the decreases were observed in both acyclovir and dexamethasone treated groups even though the expressions were still higher than that of control group （P〈0.05）. The expression of IL-2 and neurological injury score were positively correlated on day 6 after infection （r=0.64, P〈0.05）. Conclusions The survival rate of HSE mice significantly increased and clinical symptom decreased with treatment of acyclovir or glucocorticoid than with antivirus treatment alone. The degree of neurological injury shows a positive correlation with the IL-2 expression in brain tissue.