首页|糖皮质激素对肺炎链球菌脑膜炎大鼠脑保护作用及脑脊液免疫球蛋白水平的影响研究

糖皮质激素对肺炎链球菌脑膜炎大鼠脑保护作用及脑脊液免疫球蛋白水平的影响研究

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目的:探究糖皮质激素对肺炎链球菌(SP)脑膜炎模型大鼠脑损伤的影响,以及该作用下脑脊液免疫球蛋白水平的变化.方法:将40只SD大鼠按数字随机表法分为对照组、模型组、低剂量甲泼尼龙琥珀酸钠组(Low-MSS)、高剂量甲泼尼龙琥珀酸钠组(High-MSS),每组10只.除对照组外,其余各组大鼠构建SP脑膜炎模型,Low-MSS组和High-MSS组大鼠分别以5 mg/kg、10 mg/kg剂量尾静脉注射甲泼尼龙琥珀酸钠,1次/d,持续21 d.采用Loeffler法对造模后的大鼠进行神经行为学评分;免疫比浊法检测大鼠脑脊液免疫球蛋白IgA、IgM及IgG含量;ELISA测定大鼠脑匀浆上清中炎症细胞因子TNF-α、IL-6及IFN-γ水平;HE染色检测大鼠脑组织病理学形态变化;Nissl染色检测大鼠脑组织神经元细胞数目;TUNEL染色检测大鼠脑组织细胞凋亡数目;免疫荧光染色检测大鼠脑组织损伤标志蛋白GFAP与S-100b表达.结果:注射SP前,对照组和模型组大鼠神经行为学评分差异无统计学意义(P>0.05),注射SP后24 h、48 h、72 h,模型组大鼠神经行为学评分显著低于对照组(P<0.05).与对照组比较,模型组大鼠脑脊液中IgA、IgM及IgG含量均升高,脑匀浆上清中TNF-α、IL-6及IFN-γ含量也均升高,脑组织发生明显病变损伤,伴随大量炎症细胞浸润,神经元细胞减少,凋亡细胞数增加,S-100b与GFAP的荧光密度值升高(P<0.05);与模型组比较,Low-MSS组和High-MSS组大鼠脑脊液中IgA、IgM及IgG含量均降低,脑匀浆上清中TNF-α、IL-6、IFN-γ含量也均降低(P<0.05),脑组织损伤现象得到缓解,炎症细胞浸润明显减少,神经元细胞增多,凋亡细胞数目减少,S-100b与GFAP的荧光密度值也均下降(P<0.05).此外,High-MSS组对各项指标及脑组织损伤的改善效果要优于Low-MSS组(P<0.05).结论:糖皮质激素甲泼尼龙琥珀酸钠可有效改善SP脑膜炎大鼠的脑组织损伤,并能够调节免疫球蛋白IgA、IgM及IgG水平,对SP脑膜炎大鼠起到保护作用.
Effects of glucocorticoids on brain protection and cerebrospinal fluid immunoglobulin levels in rats with Streptococcus pneumoniae meningitis
Objective:To investigate the effect of glucocorticoids on brain injury in rats with Streptococcus pneumoniae(SP)meningitis,as well as the changes of cerebrospinal fluid immunoglobulin levels under this effect.Methods:A total of 40 SD rats were divided into control group,model group,low-dose methylprednisolone sodium succinate group(Low-MSS)and high-dose methylpred-nisolone sodium succinate group(High-MSS)according to random table method,with 10 rats in each group.Except for the control group,SP meningitis models were established in other groups.Rats in Low-MSS group and High-MSS group were injected with methyl-prednisolone sodium succinate by tail vein at doses of 5 mg/kg and 10 mg/kg,respectively,once a day for 21 days.Neurobehavioral scores of rats after modeling were performed by Loeffler method;contents of immunoglobulin IgA,IgM and IgG in cerebrospinal fluid of rats were detected by immunoturbidimetry;levels of inflammatory cytokines TNF-α,IL-6 and IFN-γ in supernatant of rats brain ho-mogenate were determined by ELISA;HE staining was used to detect pathological changes of rats brain tissue;Nissl staining was used to detect the number of neuronal cells in rats brain tissue;TUNEL staining was used to detect the number of apoptotic cells in rats brain tissue;immunofluorescence staining was used to detect expressions of GFAP and S-100b,the marker proteins of rat brain tissue injury.Results:Before SP injection,there was no difference in neurobehavioral scores between control group and model group(P>0.05),at 24 h,48 h and 72 h after SP injection,neurobehavioral scores in model group were significantly lower than those in control group(P<0.05).Compared with control group,contents of IgA,IgM and IgG in cerebrospinal fluid of rats in model group were in-creased,and contents of TNF-α,IL-6 and IFN-γ in supernatant of the brain homogenate were also increased,the tissue was obviously damaged,accompanied by a large number of inflammatory cells infiltration,the number of neuronal cells were decreased,the number of apoptotic cells were increased,and the fluorescence density values of S-100b and GFAP were increased(P<0.05);compared with model group,contents of IgA,IgM and IgG in cerebrospinal fluid of rats in Low-MSS group and High-MSS group were decreased,and contents of TNF-α,IL-6 and IFN-γ in brain homogenate supernatant were also decreased(P<0.05),brain tissue damage was alleviated,inflammatory cell infiltration was significantly reduced,neuronal cells were increased,the number of apoptotic cells were decreased,and the fluorescence density values of S-100b and GFAP were also decreased(P<0.05).In addition,the improvement effect of various indexes and brain tissue damage in High-MSS group was better than that in Low-MSS group,and the difference were statistically signifi-cant(P<0.05).Conclusion:Glucocorticoid methylprednisolone sodium succinate can effectively improve the brain tissue damage in SP meningitis rats,regulate the levels of immunoglobulin IgA,IgM and IgG,and has a protective effect on SP meningitis rats.

Streptococcus pneumoniae meningitisGlucocorticoidsImmunoglobulins

肖林婷、周少珑、周辉、蔡奕秋、陈薇

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三亚市人民医院神经内科,三亚 572000

肺炎链球菌脑膜炎 糖皮质激素 免疫球蛋白

海南省卫生健康行业科研项目

21A200330

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(6)
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