糖皮质激素对单纯疱疹病毒性脑炎发病及预后影响的动态观察

The glucocorticoid therapy for herpes simplex virus encephalitis in mice

目的探讨单纯疱疹病毒性脑炎(HSE)的发病机制以及阿昔洛韦和地塞米松的作用机制。方法雄性小鼠共102只,随机分为对照组、病毒感染组、阿昔洛韦组和联合用药组。采用颅内注射单纯疱疹病毒-1型建立HSE小鼠模型;颅内注射后第1天,阿昔洛韦组和联合用药组小鼠给予阿昔洛韦灌胃,对照组和病毒感染组给予生理盐水灌胃;颅内注射后第3天,联合用药组给予地塞米松腹腔注射,余组给予生理盐水腹腔注射。分别于模型建立后第3、6、9天行神经症状评分,并用免疫组化法测定小鼠脑组织中IL-2、IL-10的表达,HE染色比较脑组织病理变化。结果病毒感染组生存率最低,阿昔洛韦组次之,联合用药组最高(P<0.05)。第3、6、9天的神经症状评分均以病毒感染组最高,阿昔洛韦组次之,联合用药组最低(P<0.05)。小鼠脑组织病理和HE染色也显示同样的情况。第3、6、9天,小鼠脑内IL-2呈现先升高后下降的趋势,而IL-10呈逐渐上升趋势;在各时间点,各组小鼠间IL-2、IL-10表达差异均有统计学意义(P<0.05),其中均以病毒感染组高于阿昔洛韦组,阿昔洛韦组高于联合用药组(P均<0.05);而联合用药组与对照组差异无统计学意义(P>0.05)。结论糖皮质激素联合抗病毒药物治疗HSE,较单纯阿昔洛韦治疗更能减少脑组织中IL-2、IL-10的分泌,减轻临床症状,提高生存率。

Abstract： Objectives To investigate the pathogenic mechanism of herpes simplex encephalitis （HSE） and the mecha- nism of action of dexamethasone and aeyclovir. Methods 102 male mice were randomly assigned to normal control group, HSV-1 infection group, acyclovir-treated group and combination-treated group. The model of HSE was established by in- tracranial injection of HSV-1 in mice except normal controls. One day after intracranial injection, mice in acyclovir-treated group and combination-treated group were intragastrically administrated with acyclovir, and mice in normal control group and HSV-1 infection group were intragastrically administrated with normal saline. Three days after intracranial injection, mice in combination-treated group were intraperitoneally injected with dexamethasone and mice in other groups were in- traperitoneally injected with normal saline. The neurological injury score and the expressions of IL-2 and IL-10 of the mice brain tissues in each group were compared at 3, 6 and 9 days after model establishment. Results The survival rate of mice was lowest in HSV-1 infection group and highest in combination-treated group （P〈0.05）. The neurological injury scores at 3, 6 and 9 days were highest in HSV-1 infection group and lowest in the combination-treated group （P〈0.05）. The changes in brain tissue pathology and HE staining were closely corresponded to the neurological injury scores, At 3, 6 and 9 days, the expression of IL-2 was increased at first and then decreascd, but the expression of IL-10 was gradually increased. The expressions of IL-2 and IL-10 were highest in HSV-1 infection group and lowest in combination-treated group. And differ- ences were significant among all groups at each time point （P〈0.05） except between combination-treated group and normal control group （P〉0.05）. Conclusions In comparison with acyclovir monotherapy, combined treatment with dexamethasone and acyclovir for HSE can reduce the expression of IL-2 and 1L-10, relieve the clinical symptoms, and increase the survivalrate.