【作者】 黄鹏；

【导师】 范书铎；

【作者基本信息】 中国医科大学 ， 生理学， 2004， 硕士

【摘要】 前言 中药是中华民族的宝贵财富，前人早已发现中药有药效可靠平缓、副作用小的特点。近年不断有新药开发出来。抗感2号就是新近开发的中药复方制剂，其主要成份有葛根、连翘、穿心莲、藿香等。在国内申报新药之前，我们运用生理学和药理学方法对其进行了解热、镇痛、抗炎、体外抑菌等方面的药效学研究。本论文主要研究抗感2号在解热、镇痛方面作用并从中枢发热介质的角度探讨其解热的化学信息传递机制。为抗感2号的临床应用和进一步开发利用提供实验依据和理论基础。 实验材料 1．实验对象：健康雄性Wistar系大鼠、健康昆明种小鼠 2．实验试剂及用药：抗感2号粉剂；干酵母；2，4-二硝基苯酚；巴米尔；液氮及氮气；cAMP放免测定药盒 3．实验仪器：数字型温度计(SY-2型)；热板测痛仪(GS-840型)；液体闪烁计数仪(LS6500型) 实验方法 1．酵母发热实验：实验动物分六组：正常对照组、模型组、阳性药组(200m／kg)、中药三个剂量组(217mg／kg、435mg／kg、870mg／kg)。用干酵母复制发热动物模型，用三种剂量抗感2号观察其对发热的影响，并用阳性药物作对照。 2．2，4-二硝基苯酚发热实验：动物分组同上，阳性药组(100mg／kg)，中药三个剂量(109mg／kg、217mg／kg、435mg／kg)。与上一实验不同的是，造模前各组做预防给药连续灌胃三天。 3．醋酸致痛扭体实验：小鼠随机分成六组：正常对照组、阳性对照组、中药四个剂量组(742mg／kg、1484mg／kg、2968mg／kg、5936mg／kg)。向小鼠腹腔注射醋酸溶液复制疼痛模型，观察抗感2号对疼痛的影响。 4.热板致痛实验:动物分组同前，通过测量小鼠痛闭值的变化，观察其对疼痛的影响。 5.大鼠下丘脑组织cAMP含量测定实验:发热实验部分同实验1，动物分四组:正常对照组、模型组、中药两组(217m扩kg、435m群kg)。测温至6h断头处死动物，取出下丘脑组织投人液氮中固定，按试剂盒说明书进行cAMP含量的测定。结果 在酵母性发热实验中，模型组与正常组相比体温变化值P<0.001，中药组与模型组相比，温差有统计学意义，抗感2号能显著抑制大鼠体温升高(P<0.01)。其中中剂量组(435m扩kg)效果最好(P<0.001)。该药还能预防2，4一二硝基苯酚所致大鼠发热。药物镇痛方面，其对醋酸致痛小鼠扭体反应有明显的抑制作用(P<0.001)，对热板法致痛有明显提高痛阑值作用(P<0.01)，且呈量效关系。模型组下丘脑组织cAMP含量升高(P<0.05)，中药组与模型组相比，抗感2号能抑制cAMP含量的升高(P<0.05)。结论1.本实验证明了中药抗感2号对酵母和2，4一二硝基苯酚性发热大鼠有明显的解热作用，并有一定量效关系。.抗感2号对醋酸致小鼠扭体和热板致痛都有明显抑制和镇痛作用。.抗感2号可明显抑制酵母性发热时下丘脑组织中cAMP含量的升局。 4.实验结果提示:抗感2号可通过抑制下丘脑组织中cAMP含量的升高，而发挥其解热作用。更多还原

【Abstract】 The Chinese traditional medicine is our precious treasure. Recently more and more new herbs have been impoldered. The anti-fever 2 whose main components are Puerariae Eordythia Andrographis Paniculata and Agastache is just a new compound agent. Before reporting it to a higher authority, we take physiological and pharmacological methods to observe its antipyretic analgesic anti-inflammatory in vitro bacterisostatic effects. This paper mainly talk over the antipyretic and analgesic effects of anti-fever 2 on laboratory animals and how it brings into full play. Our purpose is to introduce experimental thereunder and theoretic base for clinical use and further usage.Materials1. Animal; male Wistar rats^KunMing mice2. Drug: anti-fever 2 powder dry yeast Dinitrophenol Aspirin liguid nitro-gon Nitrogen gas cAMP radioimmunoassay Test Kit3. Instrument: digital thermometer ( SY-2 ) pain threshold detector ( GS-840) Jiquid scintillator(LS6500)Methods1. Fever induced by yeast: The animals were divided into six groups: control group, model group, positive drug group (200mg/kg) , three herb groups (217mg/kg, 435mg/kg, 870mg/kg). The experiment was carried out on ratmodels by using dry-yeast as pyretogenic agent. We choose three dosage of herb to observe the antipyretic effect of anti-fever 2 and aspirin as control.2. Fever induced by dinitrophenol; Group dividing is as same as experiment 1. Drugs were administered continuously for three days as follows: positive drug (100mg/kg) , three herb groups (109mg/kg, 217mg/kg, 435mg/kg) , control group (salt water) , model group (salt water). Then we began to make models. 3. Writhing test: The mice were divided into six groups randomly: control group, positive drug group ( 300mg/kg) , four herb groups ( 742mg/kg, 1484mg/kg, 2986mg/kg, 5936mg/kg). The analgesic effect was determined with mouse writhing method of celiac acetum injecting.4. Hot plat test; Group dividing is as same as experiment 3. Through measuring the changes of pain threshold, we observed analgesic effect of anti-fever 2.5. Assay of cAMP content in hypothalamus of rats: Model building is the same as experiment 1. There were total four groups: control group, model group, two herb groups (217mg/kg, 435mg/kg). After 6 hours of yeast injection, rats were decapitated quickly and hypothalamus tissues were taken out and put into liquid nitrogen for fixation. Then we began to assay the cAMP content in hypothalamus according to specification of the Test Kit.ResultsIn the yeast inducing fever test compared with control group the changes of rats’temperature in model group are obvious (P <0. 001) . Compared with model group the changes of temperature in herb groups have statistical significance. Anti-fever 2 can significantly inhibit uprise of temperature in rats induced by yeast (P<0.01). The medial dosage (435mg/kg) has the best effect (P<0. 001). The durg can also prevent fever induced by dinitrophenol. In analgesic studies using hot plat test and writhing test on mice anti-fever 2 has obvious inhibition of ache induced by acetum(P <0. 001) and can raise pain threshold of mice on hot plat evidently ( P <0.01). Compared with control group the anti-fever can inhibit the rise of cAMP content in the hypothalamus of rats ( P < 0. 05).Conclusion1. Our test has proved that anti-fever 2 has significant antipyretic effect on fevered rats induced by dry-yeast and dinitrophenol.2. In Writhing test and hot plat test anti-fever 2 has significant analgesic effect on model mice.3. Anti-fever 2 can distinctly inhibit the rise of cAMP content in hypothala-mus tissues of fevered rats.4. These facts suggest that anti-fever 2 possesses obvious antipyretic effect on fever rats and its action may be mediated by lowering cAMP level in hypothal-amus.更多还原