米诺环素对实验性脑积水模型胶质细胞反应性增生的抑制作用

Minocycline reduces reactive hyperplasia in rat models of communicating hydrocephalus

目的探讨米诺环素对大鼠交通性脑积水模型的治疗作用。方法30只SD大鼠按随机数字表法分为模型组、米诺环素治疗组、假手术组．每组10只。前2组采用脑立体定位高岭土注入术建立大鼠交通性脑积水模型，假手术组注射等量生理盐水。术后1周米诺环素治疗组大鼠给予米诺环素腹腔注射干预[（45mg／（kg·d1]，模型组注射等量生理盐水。治疗2周后行MRI检查侧脑室体积并计算Evan’s指数：RT．PCR检测脑组织神经胶质酸性蛋白（GFAP）、同种异体移植炎症因子（AIF-1）的表达；免疫组化染色、Westernblotting检测脑组织GFAP和钙离子接头蛋白Iba-1的表达。结果3组大鼠的侧脑室体积、Evan’s指数及脑组织中GFAP、AIF-1的表达不同，总体差异有统计学意义（P〈0．05），其中假手术组、米诺环素治疗组、模型组大鼠侧脑室体积、Evan’s指数、GFAPmRNA、A1F-1mRNA的表达依次增加，差异均有统计学意义（P〈0．05）。假手术组星形细胞和小胶质细胞主要呈休眠状态，模型组呈高反应性的星形细胞和小胶质细胞，米诺环素治疗组星形细胞和小胶质细胞增生程度较轻。Westernblotting检测显示相对于模型组，米诺环素治疗组GFAP和Iba-1蛋白的表达较低，差异有统计学意义（P〈0．05）。结论米诺环素治疗并不能逆转脑积水，但可以对脑积水的进展起到延缓作用。

Objective To determine the efficacy of minocycline on reducing reactive hyperplasia in rat models of communicating hydrocephalus. Methods Thirty adult SD rats were randomly divided into hydrocephalic model group （n=10）, minocycline-treated hydrocephalic group （n=10） and sham-operated group （n=10）; rats in the first two groups were induced communicating hydrocephalus with kaolin intraventricular injections; minocycline （45 mg/kg/day） was administered to hydrocephalic rats one week after the operation; rats in the sham-operated group and hydrocephalic model group were injected with saline. The ventricular dilatation were examined by MRI and Evan＇s indexes was calculated two weeks after treatment; glial fibrillary acidic protein （GFAP） and allograft inflammatory factor （AIF-1） expressions were detected by RT-PCR; GFAP and ionized calcium-binding adaptor molecule （Iba-1） were detected by immunohistochemistry and Western blotting. Results Significant difference was noted on ventricular dilatation, Evan＇s index, and GFAP and AIF-1 expressions among the three groups （P〈0.05）; the ventricular dilatation, Evan＇s index, and GFAP and AIF-1 mRNA expressions increased accordingly in the sham-operated group, minocycline-treated hydrocephalic group and hydrocephalic model group （P〈0.05）. Astrocytes and microglias in the sham-operated group were under dormant state; astrocytes and microglias in the model group were under hyperresponsiveness, while astrocytes and microglias in the minocycline-treated hydrocephalic groupshowed slight hyperplasia. The expressions of GFAP and lba-1 in the model group were significantly higher as compared with those in the minocycline-treated hydrocephalic group （P〈0.05）. Conclusion Minocycline treatment is effective in delaying the development of hydrocephalus with prospective to be the auxiliary therapeutic method of hydrocephalus.