摘要
目的探索积雪草苷的解热作用。方法雄性SD大鼠56只,随机平均分为正常组、模型组、溶媒对照组、对乙酰氨基酚组和积雪草苷3个剂量组。除正常组外,每只大鼠ip细菌脂多糖(LPS)100μg.kg-1制备大鼠发热模型,连续6h监测大鼠体温变化,6h后取血、肝脏和脑组织标本。积雪草苷3个剂量组造模前连续3dig积雪草苷(5,15和45mg.kg-1),每日1次;正常组和模型组给予等量生理盐水;溶媒对照组给予等量0.5%羧甲基纤维素钠;对乙酰氨基酚组于造模前30min一次性给予对乙酰氨基酚(50mg.kg-1,ip)。肝组织髓过氧化物酶(MPO)活性采用MPO试剂盒检测,肝脏组织血红素氧化酶1(HO-1)和脑组织环氧合酶2(COX-2)蛋白表达采用Western印迹方法测定,血浆前列腺素E2(PGE2)含量用酶联免疫法检测,HO-1活性用Morita法检测。结果注射LPS后,模型组出现3相热,最高升温幅度为2.01℃。积雪草苷5,15和45mg.kg-1组体温明显低于模型组,其中45mg.kg-1组与对乙酰氨基酚组相当。与模型组比较,3个积雪草苷剂量组发热后6h肝组织MPO活性、脑组织COX-2蛋白表达和血浆中PGE2的产生明显降低,肝组织HO-1活性和蛋白表达升高。结论积雪草苷具有预防发热作用,该作用可能与抑制COX-2/PGE2系统,并抑制炎症因子MPO活性、增强炎症保护因子HO-1的活性和表达有关。
AIM To explore the pyretolytic effect of asiaticoside. METHODS Fifty-six male SD rats were randomly divided into normal, model, vehicle, paracetamol and 3 doses of asiaticoside groups. Rat fever model was made by ip lipopolysaccharides （LPS, 100 μg· kg^-1）. The changes of the core temperature （AT） were tested every 30 min after ip LPS, and lasted for 6 h. The rats in asiaticoside （5, 15 and 45 mg· kg^-1 ） groups were ig asiaticoside for 3 d before ip LPS. The rats of normal and model groups were ig normal saline, and rats of vehicle group were ig 0.5% carboxymethyl cellulose, instead of asiaticoside. The rats of paracetamol group were ip paracetamol （50 mg· kg^-1） only once and 30 min later ip LPS. The myeloperoxidase （MPO） activity in liver was detected with the MPO kit. The protein expressions of cyclooxygenase-2 （ COX-2 ） in brain tissue and heme oxygenase-1 （ HO-1 ） in liver tissue were analyzed with Western-blot. The prostaglandin E2 （PGE2 ） content in plasma was detected with enzyme immunoassay and the activity of HO-1 in liver tissue was detected with Morita method. RESULTS The fever appearance of the model rats had three febrile phases, and the maximum amplitude of temperature achieved 2. 01 ℃. Compared with model group, the core temperatures of rats in asiaticoside （ 5,15 and 45 mg· kg^-1 ） groups were obviously lower, and asiaticoside 45 mg· kg^-1 group was similar to paracetamol group. Asiaticoside （5,15 and 45 mg· kg^-1） obviously reduced the protein expression of COX-2 in brain, MPO activity in liver and PGE2 content in plasma. The activity and expression of HO-1 in liver were elevated after ig asiaticoside （5.15 and 45 mg· kg^-1 ）. CONCLUSION Asiaticoside has the inhibitory effect on fever, and this action possibly is related to its inhibition of the COX-2/PGE2 system, reduction of MPO activity and enhancement of the activity and expression of HO-1.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2007年第3期229-234,共6页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金资助项目(30500463)~~
关键词
积雪草苷
脂多糖类
发热
炎症
镇痛药
非麻醉
asiaticoside
lipopolysaccharides
fever
inflammation
analgesics, non-narcotic
