Tsai Cheng-Chia, Lin Mao-Tsun, Wang Jhi-Joung, Liao Jyh-Fei, Huang Wu-Tein
Institute of Pharmacology, National Yang-Ming University, and Department of Surgery, Mackay Memorial Hospital, Taipei 100, Taiwan.
Neuropharmacology. 2006 Sep;51(4):709-17. doi: 10.1016/j.neuropharm.2006.05.010. Epub 2006 Jul 14.
Evidence has accumulated to indicate that systemic administration of lipopolysaccharide (LPS), in addition to elevating tumor necrosis factor-alpha (TNF-alpha) as well as fever, induces overproduction of both glutamate and hydroxyl radicals in the rabbit's hypothalamus. Current investigation was attempted to determine whether baicalin exerts its antipyresis by suppressing overproduction of circulating TNF-alpha and hypothalamic glutamate and hydroxyl radicals in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of both glutamate and hydroxyl radicals in situ. It was found that systemic administration of LPS (0.5-10 microg/kg) induced dose-related increased levels of both core temperature and hypothalamic levels of both glutamate and hydroxyl radicals accompanied by increased plasma levels of TNF-alpha. The rise in both the core temperature and hypothalamic glutamate and hydroxyl radicals could also be induced by direct injection of TNF-alpha (1-20 ng) into the lateral ventricle of rabbit brain. Pretreatment with baicalin (2-20 mg/kg, i.v.) one hour before an i.v. dose of LPS significantly reduced the LPS-induced overproduction of circulating TNF-alpha and brain glutamate and hydroxyl radicals. Both the febrile response and overproduction of both glutamate and hydroxyl radicals in the hypothalamus caused by central administration of TNF-alpha could be suppressed by baicalin. These findings suggest that systemic administration of baicalin may exert its antipyresis by inhibiting the N-methyl-D-aspartate receptor-dependent hydroxyl radicals pathways in the hypothalamus and circulating TNF-alpha accumulation during LPS-fever.
越来越多的证据表明，全身注射脂多糖（LPS），除了会升高肿瘤坏死因子-α（TNF-α）以及引起发热外，还会导致兔下丘脑谷氨酸和羟自由基的过量产生。目前的研究旨在确定黄芩苷是否通过抑制兔体内循环TNF-α以及下丘脑谷氨酸和羟自由基的过量产生来发挥解热作用。将微透析探针立体定位并长期植入兔脑视前区下丘脑，以原位测定谷氨酸和羟自由基。研究发现，全身注射LPS（0.5 - 10微克/千克）会导致体温和下丘脑谷氨酸及羟自由基水平呈剂量相关的升高，同时血浆TNF-α水平也会升高。直接向兔脑侧脑室注射TNF-α（1 - 20纳克）也可引起体温以及下丘脑谷氨酸和羟自由基的升高。在静脉注射LPS前一小时静脉注射黄芩苷（2 - 20毫克/千克）可显著降低LPS诱导的循环TNF-α以及脑内谷氨酸和羟自由基的过量产生。黄芩苷可抑制由中枢注射TNF-α引起的发热反应以及下丘脑谷氨酸和羟自由基的过量产生。这些发现表明，全身注射黄芩苷可能通过抑制下丘脑N-甲基-D-天冬氨酸受体依赖性羟自由基途径以及LPS发热期间循环TNF-α的蓄积来发挥解热作用。
