褪黑素对新型隐球菌感染脑膜炎大鼠的脑保护作用机制研究  

Study on effect of melatonin on protection of brains of mice with Cryptococcus neoformans meningitis

作　　者：刘成业 周奋 潘德岳 云望 李钢 LIU Cheng-ye;ZHOU Fen;PAN De-yue;YUN Wang;LI Gang(Sanya Central Hospital,Sanya,Hainan 572000,China)

机构地区：[1]海南省三亚市三亚中心医院神经外科,海南三亚572000

出　　处：《中华医院感染学杂志》2020年第7期961-966,共6页Chinese Journal of Nosocomiology

基　　金：海南省卫生厅科研基金资助项目(琼卫2010-64)。

摘　　要：目的研究褪黑素对新型隐球菌感染所致的脑膜炎大鼠的脑保护作用机制。方法选取30只SD健康大鼠,随机选取30只大鼠中的10只作为正常组,剩余的20只大鼠建立新型隐球菌感染所致的脑膜炎模型,将建模成功的大鼠随机分为脑膜炎组10只和褪黑素组9只。褪黑素组大鼠将0.1%的褪黑素10 mg/kg注射于腹腔,脑膜炎组、正常组大鼠腹腔注射等剂量的生理盐水。对三组大鼠进行症状评分及脑含水量检测,并检测大鼠脑组织中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)水平、高迁移率族蛋白B1(High mobility group protein B1,HMGB1)、诱导型NOS(Inducible NOS,iNOS)蛋白相对表达量。结果褪黑素组脑组织中炎性因子TNF-α、IL-6、IL-8水平分别为(216.98±13.27)pg/ml、(98.67±8.23)μg/g、(53.27±4.12)μg/g均低于脑膜炎组(773.69±20.68)pg/ml、(163.59±12.58)μg/g、(83.69±6.59)μg/g(P<0.05)。褪黑素组脑组织中HMGB1、iNOS蛋白相对表达量为(1.00±0.20)、(0.98±0.18)均低于脑膜炎组(1.56±0.32)、(1.62±0.37)(P<0.05)。结论褪黑素通过作用于炎性介质HMGB1、iNOS蛋白,进而抑制炎性因子的异常表达,降低脑部炎症反应,进而对新型隐球菌感染所致的脑膜炎大鼠脑组织起到保护作用。OBJECTIVE To study the protective effect of melatonin on the meningitis caused by Cryptococcus neoformans infection in rats.METHODS Thirty SD healthy rats were selected,10 of which were randomly divided into the normal group.The remaining 20 rats were infected by C.neoformans to establish the meningitis model.Nineteen rats successfully modeled were randomly divided into the meningitis group(10 rats)and the melatonin group(9 rats).Rats in the melatonin group were administered the dosage of 10 mg/kg with 0.1%melatonin into the abdominal cavity;rats in the meningitis group and the normal group were injected with saline.The symptom score and brain water content in the three groups of rats were evaluated.The expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-8(IL-8),high mobility group protein B1(HMGB1)and inducible NOS(iNOS)in the brain of the rats were quantitatively detected.RESULTS The levels of TNF-α,IL-6 and IL-8 in the melatonin group were(216.98±13.27 pg/ml,98.67±8.23μg/g,53.27±4.12μg/g)significantly lower than that in the meningitis group(773.69±20.68 pg/ml,163.59±12.58μg/g,83.69±6.59μg/g)(P<0.05).The relative expression of HMGB1 and iNOS protein in the melatonin group was(1.00±0.20,0.98±0.18)significantly lower than that in the meningitis group(1.56±0.32,1.62±0.37)(P<0.05).CONCLUSION Melatonin can inhibit the abnormal expression of inflammatory factors by acting on the inflammatory mediators HMGB1 and iNOS proteins,and reduce the inflammatory reaction in the brain,thus protecting the brain tissue of rats against meningitis caused by C.neoformans infection.

关 键 词：褪黑素 新型隐球菌感染 脑膜炎 脑保护作用 

分 类 号：R512.3[医药卫生—内科学]