Lorenzl S, Koedel U, Frei K, Bernatowicz A, Fontana A, Pfister H W
Department of Neurology, Klinikum Grosshadern Ludwig-Maximilians-University of Munich, Germany.
J Infect Dis. 1995 Jul;172(1):113-8. doi: 10.1093/infdis/172.1.113.
This study investigated whether the 21-aminosteroid U74389F, an inhibitor of lipid peroxidation, attenuates pathophysiologic changes in experimental pneumococcal meningitis. Infected rats injected intravenously with vehicle of [corrected] U74389F developed increases in regional cerebral blood flow (rCBF), intracranial pressure (ICP), brain water content, and white blood cells (WBC) in cerebrospinal fluid (CSF) within 8 h after intracisternal challenge. Pretreatment with or administration of U74389F 4 h after infection significantly reduced the increase in ICP but had no effect on rCBF increase. Moreover, U74389F pretreatment significantly reduced brain water content and CSF WBC count. In vitro, U74389F inhibited iron-dependent lipid peroxidation of astrocyte cultures and the production of tumor necrosis factor-alpha, interleukin-6, and nitric oxide by stimulated macrophages. These data suggest that U74389F modulates early pathophysiologic alterations in experimental pneumococcal meningitis.
本研究调查了脂质过氧化抑制剂21-氨基类固醇U74389F是否能减轻实验性肺炎球菌性脑膜炎的病理生理变化。经脑池内攻击后8小时内，静脉注射U74389F赋形剂的感染大鼠出现局部脑血流量（rCBF）、颅内压（ICP）、脑含水量增加，以及脑脊液（CSF）中白细胞（WBC）增多。感染后4小时用U74389F预处理或给药可显著降低ICP的升高，但对rCBF的增加无影响。此外，U74389F预处理可显著降低脑含水量和CSF白细胞计数。在体外，U74389F可抑制星形胶质细胞培养物中铁依赖性脂质过氧化，以及刺激的巨噬细胞产生肿瘤坏死因子-α、白细胞介素-6和一氧化氮。这些数据表明，U74389F可调节实验性肺炎球菌性脑膜炎的早期病理生理改变。
