黄芩苷对兔大肠杆菌脑膜炎的辅助治疗作用及机制探讨

Neuroprotective effect of adjunctive baicalin therapy on E.coli meningitis in rabbits and its mechanism

目的探讨黄芩苷对兔大肠杆菌脑膜炎的辅助治疗作用及机制。方法24只家兔随机均分为4组:正常对照(CON)组、脑膜炎模型(MOD)组、氨苄治疗(AMP)组和氨苄+黄芩苷治疗(BAI)组。MOD组、AMP组、BMI组均经小脑延髓池接种E.coli混悬液0.5ml制备脑膜炎模型,CON组则注入等量生理盐水。MOD组CON组均不做任何治疗。AMP组于注菌后14h注射氨苄青霉素(200mg/kg);BAI组在注射氨苄青霉素的同时给予黄芩苷(20ml/kg)。在注菌前、治疗前、治疗后5h分别测定脑脊液(CSF)中白细胞数、蛋白质、乳酸、白细胞介素-1(IL-1)和肿瘤坏死因子-α(TNF-α),并测定治疗后的脑组织含水量。结果治疗前MOD组、AMP组和BAI组间白细胞数、蛋白质、乳酸、IL-1和TNF-α水平无统计学差异(P>0.05),但均高于CON组(P<0.01);治疗后MOD组、AMP组、BAI组均高于CON组(P<0.01);BAI组低于MOD组、AMP组(P<0.05);BAI组较治疗前下降(P<0.01);CSF中白细胞数、蛋白质,AMP组高于MOD组(P<0.05),AMP组较治疗前升高(P<0.01);脑组织含水量,MOD组、AMP组、BAI组均高于CON组(P<0.01),BAI组低于MOD组、AMP组(P<0.05)。结论黄芩苷辅助治疗E.coli脑膜炎可显著减轻单纯氨苄青霉素治疗早期所致的脑膜炎症反应,其机制与CSF中IL-1、TNF-α等炎性因子减少有关。

Objective To explore the neuroprotective effects of baicalin as an adjunctive therapeutic agent on E. coli meningitis in rabbits and its underlying mechanisms. Methods Twenty four adult rabbits were randomly divided into 4 groups： normal control （CON） group, meningitis model （MOD） group, ampicillin treatment （AMP） group and ampicillin ＋ baicalin treatment （BAD group. Rabbits in MOD, AMP and BMI group were inoculated with 0.5ml of E. coli suspension into cisterna cerebellomedullaris to reproduce the meningitis model, while those in CON group with equal volume of normal saline was given instead. Rabbits in MOD and CON group received no treatment, while animals in AMP group were treated with AMP, and those in BAI group were treated with ampieillin plus baicalin. Leucocyte, protein, lactic acid, interleukin-1 （IL-1） and tumor necrosis factor a （TNF-α） in eerebrospinal fluid （CSF） were measured before E. coli inoculation, before treatment and 5 hours after treatment. The water content of brain tissue was also determined after treatment. Results No significant difference existed in leucocyte count, and protein, lactic acid, IL-1 and TNF-α levels among MOD, AMP and BAI groups before treatment, but all the indexes were significantly higher compared with that in CON group （P〈0. 01）. Five hours after treatment, these indexes in group MOD, AMP, and BAI were still higher than that in CON group （P〈0. 01）. These indexes declined after treatment （P〈0. 01）, and they were lower in BAI group than those in MOD and AMP group （P〈0. 05）. Leucocyte count and protein in CSF increased after treatment （P〈0. 01） and was significantly higher in AMP groups than in MOD group （P〈0. 05）. The water content of brain tissue was higher in MOD, AMP and BAI groups than in CON group （P〈0.01）, and was lower in BAI group compared with MOD and AMP group （P〈0. 05）. Conclusion As an adjunctive treatment, baicalin may abate the incipient inflammatory reaction of E. coli bacterial meningitis induced by simple arnpicillin treatment, the mechanism might be related to the decrease of IL-1 and TNF-α in CSF.