论文标题:注射用清开灵冻干粉解热抗炎作用及解热机制研究
The Antipyretic and Anti-inflammatory Effects of Qingkailing Freeze-dried Powder for Injection and Its Antipyretic Mechanism
论文作者
论文导师 杨芳炬,论文学位 硕士,论文专业 药理学
论文单位 四川大学,点击次数 84,论文页数 47页File Size1943K
2007-05-01论文网 http://www.lw23.com/lunwen_958290197/
Qingkailing Freeze-dried Powder for Injection(QI);; Antipyretic Effects;; Anti-inflammatory Effects;; IL-1β;; cAMP
目的通过建立家兔2，4-二硝基苯酚发热模型及大鼠内毒素发热模型，观察不同剂量清开灵冻干粉浓缩液注射给药后对不同种属动物体温变化的影响；建立角叉菜胶致大鼠足趾肿胀模型，观察不同剂量清开灵冻干粉浓缩液注射给药后对大鼠足趾肿胀程度的影响。在内毒素发热模型中，用放免法观察对大鼠下丘脑白细胞介素-1β(IL-1β)及环磷酸腺苷(cAMP)含量的影响。从而评价注射用清开灵冻干粉的解热、抗炎作用，探讨其解热作用的机制。 方法采用家兔背部皮下注射2，4-二硝基苯酚乙醇溶液制备2，4-二硝基苯酚性发热模型。将纯种大耳白兔随机分为安乃近组(阳性对照组)，生理盐水组(阴性对照组)，清开灵冻干粉大、中、小剂量(74.50mg／kg，37.25mg／kg，18.625mg／kg)组。测量基础体温并经耳缘静脉给药，10分钟后自家兔背部皮下注射2％2，4-二硝基苯酚乙醇溶液1.50mg／kg造成发热模型。测量造模后30min、1、2、3、4、6h体温变化，以体温和基础体温之差作为结果指标。采用大鼠腹腔注射内毒素溶液制备内毒素性发热模型。将SD大鼠随机分为安乃近组(阳性对照组)，生理盐水组(阴性对照组)，清开灵冻干粉大、小剂量(298.00mg／kg，149.00mg／kg)组。测量基础体温并经尾静脉给药，10分钟后自大鼠腹腔注射内毒素溶液50μg／kg造成发热模型。测量造模后20min、40min、1h体温变化，以体温和基础体温之差作为结果指标。于末次测量体温后，处死动物，取出下丘脑，纵向切成二等份，分别用于测量下丘脑IL-1β含量与cAMP含量，测量方法为放射性免疫法。采用大鼠足趾内注射角叉菜胶溶液制备大鼠足趾肿胀模型。将雄性SD大鼠随机分为地塞米松组(阳性对照组)，生理盐水组(阴性对照组)，清开灵冻干粉大、中、小剂量(298.00mg／kg，149.00mg／kg，74.50mg／kg)组。尾静脉给药并自大鼠足趾中部皮下注入0.15ml 1％角叉菜胶溶液。并于注入后30分钟、1小时、2小时、3小时、4小时、5小时用千分尺测定其左后足趾厚度作为大鼠足趾肿胀程度指标，并进行组间比较。 结果注射用清开灵冻干粉能有效抑制内毒素导致的大鼠发热(P＜0.01)及2，4-二硝基苯酚导致的家兔发热(P＜0.01)，显著降低发热大鼠下丘脑IL-1β(P＜0.01)及cAMP(P＜0.01)的含量。注射用清开灵冻干粉能明显减轻角叉菜胶致大鼠足趾肿胀程度(P＜0.01)。 结论注射用清开灵冻干粉具有解热、抗炎的作用，其解热机制可能是通过抑制内生致热原IL-1β的生成，从而降低下丘脑发热介质cAMP的含量。
Objective By the rabbit model of 2,4-dinitrophenol-induced fever and the rat model of endotoxin-induced fever, to investigate the antipyretic effects of different doses of Qingkailing Freeze-dried Powder for Injection (QI). By the rat model of hind paw edema induced by carrageenan, to investigate the anti-inflammatory effects of different doses of Qingkailing Freeze-dried Powder for Injection(QI). In the endotoxin-induced fever, radioimmunoassay was adopted to detect the levels of IL-1βand cAMP in the hypothalamus of rats. The aim is to evaluate the antipyretic effects and anti-inflammatory effects of Qingkailing Freeze-dried Powder for Injection (QI) and its mechanism of the antipyretic effect. Methods The rabbit model of 2,4-dinitrophenol-induced fever was adopted to prepare model of fever caused by 2,4-dinitrophenol. Pure breed of rabbits were grouped into five random groups, i.e. analgin group(positive control)、NS group(negative control)、Qingkailing Freeze-dried Powder groups(74.50mg/kg, 37.25mg/kg, 18.625mg/kg). Basal body temperature was measured and intravenous injection of drugs was administered, and 10 minutes later, subcutaneous injection of 2,4-dinitrophenol(1.50mg/kg)was administered to prepare model of fever caused by 2,4-dinitrophenol.30minutes、1、2、3、4 and 6 hours later, the changes of body temperature were measured and the differences between body temperature and basal body temperature were taken as the result. The rat model of endotoxin-induced fever was established to prepare model of fever caused by endotoxin. Rats were grouped into four random groups, i.e. analgin group(positive control)、NS group(negative control)、Qingkailing Freeze-dried Powder groups(298.00mg/ kg, 149.00mg/kg). Basal body temperature was measured and intravenous injection of drugs was administered, and 10 minutes later, intraperitoneal injection of endotoxin(50μg/kg) was administered to prepare model of fever caused by endotoxin. 20、40 minutes and 1 hours later, the changes of body temperature were measured and the differences between body temperature and basal body temperature were taken as the result. Then, rats were killed and the hypothalamuses were taken out of. Radioimmunoassay was adopted to detect the levels of IL-1βand cAMP in the hypothalamus of rats. The anti-inflammatory effects were observed in rats with hind paw edema induced by carrageenan. Male rats were grouped into five random groups, i.e. hexadecadrol group(positive control)、NS group(negative control)、Qingkailing Freeze-dried Powder groups(298.00mg/kg, 149.00mg/kg, 74.50mg/kg). Intravenous injection of drugs was administered, and hypodermic injection of carrageenan was administered to prepare model of hind paw edema induced by carrageenan. 30minutes、1、2、3、4 and 5 hours later, the thicknesses were measured and the increases of thickness after inflammation were taken as the result. Results QI showed marked antipyretic effects on the 2,4-dinitrophenol-induced fever and the endotoxin-induced fever. At the same time, QI remarkably decreased the contents of IL-1βand cAMP in the hypothalamus. QI also remarkably lessen the degree of carrageenan-induced paw edema. Conclusions QI has antipyretic and anti-inflammatory effects. Its mechanism of the antipyretic effect on rats may be the inhibiting of the production of IL-1βand accordingly decreasing cAMP in the hypothalamus.
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