虎杖苷对化脓性脑膜炎的神经保护作用及机制研究

摘要

目的：探讨虎杖苷对化脓性脑膜炎的神经保护作用及机制。方法选取60只新西兰兔，随机将其均分为正常对照组、脑膜炎组、单用虎杖苷组、单用氨苄青霉素组、虎杖苷＋氨苄青霉素组、地塞米松＋氨苄青霉素组，每组各10只。采用将0．5 mL埃希氏大肠杆菌直接接种于兔小脑延髓池的方法，复制脑膜炎模型。分别给予各组生理盐水、虎杖苷、氨苄青霉素、虎杖苷＋氨苄青霉素、地塞米松＋氨苄青霉素治疗。各组动物均于接种或注入生理盐水后24 h （用药前）、27 h、30 h、36 h采集脑脊液，进行白细胞、蛋白、TNF－α和IL－1β含量测定。各组动物于接种后36 h采用免疫组化法检测脑组织p－p38丝裂原激活蛋白激酶（ p－p38MAPK）表达。结果与正常对照组比较，脑膜炎组在接种后24 h（用药前）、27 h、30 h、36 h脑脊液中白细胞计数、蛋白、TNF－α和IL－1含量明显增多，差异有统计学意义（ P＜0．05）。与脑膜炎组比较，各治疗组指标在相应各时间点均明显减少，差异有统计学意义（P＜0．05）。与正常对照组比较，脑膜炎组在接种后36h p－p38MAPK的表达明显增多，差异有统计学意义（P＜0．05）。与脑膜炎组比较，各治疗组p－p38MAPK表达明显减少，差异有统计学意义（ P＜0．05）。虎杖苷＋氨苄青霉素组p－p38MAPK表达较其他治疗组低，差异有统计学意义（ P＜0．05）。虎杖苷＋氨苄青霉素组和地塞米松＋氨苄青霉素组之间上述指标差异无统计学意义，但两组均较单用虎杖苷组、单用氨苄青霉素组上述指标降低的程度更加明显，差异有统计学意义（P＜0．05）。结论虎杖苷可以降低兔大肠杆菌脑膜炎脑脊液中TNF－α和IL－1β的浓度，对脑组织有保护作用，该作用可能与下调p－p38MAPK的表达有关。%ObjectiveToexploretheneuroprotectiveeffectofPolydatinonsuppurativemeningitisanditsmechanism.Methods 60 adult rabbits were randomly divided into 6 groups:normal control group, meningitis group, ampicillin treatment group, Polydatin treatment group, Polydatin+ampicillin treatment group and dexamethasone+ampicillin treatment group.Rabbits in groups except normal control group were inoculated with 0.5 mL E.coli into medulla oblongata to reproduce the meningitis model.Rabbits in normal control group and meningitis model group received normal saline, and those in the rest of groups were treated with corresponding drugs according to grouping instead.Leucocyte, protein, interleukin-1β( IL-1β) and tumor necrosis factorα( TNF-α) in cerebrospinal fluid( CSF) were measured after E.coli inoculation 24 hours, 27 hours,30 hours and 36 hours.The p-p38 mitogen activated protein kinase( p-p38 MAPK) was also determined after E.coli inoculation 36 hours.Results All the indexes were significantly higher in meningitis model group compared with that in normal control group (P<0.05).All the indexes were significantly lower in groups expect meningitis model group and normal con-trol group compared with that in meningitis model group after E.coli inoculation 27 hours,30 hours and 36 hours (P<0.05).The expre-ssion of p-p38 MAPK was higher in meningitis model group than in normal control group after E.coli inoculation 36 hours.Compared with normal control group, treatment groups reduced the expression of p-p38 MAPK.No significant difference existed in all the indexes among ampicillin+Polydatin treatment group andampicillin+dexamethasone treatment group after treatment, but all the indexes were significantly lower compared with that in ampicillin treatment group and Polydatin treatment group (P<0.05).Conclusion Polydatin might decrease IL-1βand TNF-αin CSF of E.coli bacterial meningitis, and had neuroprotective effect.The mechanism might be related with the down-regulated the expression of p-p38 MAPK.