| 余 良,张 婵,田锐锋,韩 星,赵丽芳,陈晓燕.高迁移率族蛋白1拮抗剂BoxA对细菌性脑膜炎大鼠的治疗作用[J].,2020,(10):1811-1814 |
| 高迁移率族蛋白1拮抗剂BoxA对细菌性脑膜炎大鼠的治疗作用 |
| Effect of High Mobility Group Protein 1 Antagonist BoxA on the Treatment of Bacterial Meningitis in Rats |
| 投稿时间：2019-11-19 修订日期：2019-12-15 |
| DOI：10.13241/j.cnki.pmb.2020.10.003 |
| 中文关键词: 细菌性脑膜炎 大肠杆菌 BoxA 高迁移率族蛋白1 炎症 |
| 英文关键词: Bacterial meningitis E. coli BoxA High mobility group protein 1 Inflammation |
| 基金项目:国家自然科学基金面上项目（81172396） |
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| 中文摘要: |
| 摘要 目的：探究高迁移率族蛋白1(HMGB1)拮抗剂BoxA尾静脉注射对细菌性脑膜炎（BM）大鼠模型的临床体征改善和炎症抑制作用。方法：除外正常对照的雄性Sprague-Dawley（SD）大鼠设为对照组（n=20）, 另取60只大鼠行脑室立体定向注射20 μL 大肠杆菌Escherichia coli (DH5α 1×107 CFU/mL)建立BM模型，之后随机分为两组(各组n=30)，一组尾静脉注射HMGB1拮抗剂BoxA，即BoxA组；一组麻醉后进行尾静脉注射无菌磷酸盐（PBS），即Vehicle组。造模3 d后，对各组大鼠的临床指标以及病理生理参数 (颅内压和脑脊液白细胞（WBC）计数)进行评估，使用酶联免疫吸附实验（ELISA）法检测血清中HMGB1的相对含量，使用伊文思蓝染色观察血脑屏障(BBB)通透性，使用免疫荧光染色检测大脑皮层炎症因子（IL-1β和TNF-α）的表达水平。结果：相比Control组，Vehicle组临床指标，颅内压，WBC计数以及血清HMGB1含量明显提升（P<0.05）；而BoxA组相比Vehicle组，以上改变有部分减少（P<0.05）。另外，Vehicle组较Control组EB渗漏增加且炎症因子（IL-1β和TNF-α）表达水平增高(P<0.05)。与Vehicle组相比，BoxA组的这些变化亦被部分调节(P<0.05)。结论：HMGB1抑制剂BoxA尾静脉注射能够下调HMGB1表达水平并同时缓解细菌性脑膜炎大鼠的临床症状和炎症反应。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of high mobility group protein 1(HMGB1) antagonist BoxA via tail vein injection on the improvement of clinical signs and anti-inflammatory effects in a rat model of bacterial meningitis (BM). Methods: Male Sprague-Dawley (SD) rats were used and the normal rats were set as the control group (n=20). Another sixty rats were injected with Escherichia coli (DH5α 1×107 CFU/mL) to establish BM rat model and then were randomly divided into two groups (n=30): after anesthesia one group received intravenous BoxA (BoxA group), the other one received PBS injection as placebo (Vehicle group). Three days after model establishment, the clinical index of each group and pathophysiological parameters (intracranial pressure and CSF white blood cells (WBC) count) were evaluated, Enzyme-linked immunosorbent assay (ELISA) method were used to detect the relative serum HMGB1 content, Evans blue staining were used to observe the blood-brain barrier (BBB) permeability, immunofluorescence staining were used to detect the expression level of cerebral inflammation cytokines (IL-1β and TNF-α). Results: Compared with Control group, clinical indicators, intracranial pressure, WBC count and serum HMGB1 content in Vehicle group has significantly increased (P<0.05). These changes were partially reduced in the BoxA group compared to the Vehicle group (P<0.05). In addition, Vehicle group showed increased EB leakage and increased expression of inflammatory factors (IL-1β and TNF-α) than Control group (P<0.05). These changes were also partially adjusted in the BoxA group compared to the Vehicle group (P<0.05). Conclusion: Tail vein injection of HMGB1's inhibitor BoxA can down-regulate HMGB1 expression and alleviate the clinical symptoms and inflammatory responses in BM rats. |
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