葛根素對大鼠體溫調節作用之研究; Studies of puerarin on thermoregulatory response in rats

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 藥學院 > 中國藥學研究所(已停用) > 博碩士論文 > Item 310903500/23872

請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/23872

題名:	葛根素對大鼠體溫調節作用之研究;Studies of puerarin on thermoregulatory response in rats
作者:	邵立珠;Shao Li-Chu
貢獻者:	中國醫藥學院中國藥學研究所
日期:	1999
上傳時間:	2009-11-26 11:58:57 (UTC+8)
摘要:	葛根素 (puerarin) 為野葛 (Pueraria lobata) 主要活性成分之一，係 isoflavones 類化合物，是中醫臨床上常用之清熱解表藥物，已知為 beta-adrenergic receptor 阻斷劑，具有解痙、抗心率不整、降血壓等作用，此外還具有解熱等作用，但有關 puerarin 解熱降溫作用之機轉至今仍並未見有研究報告提出；因此本研究擬就 puerarin 對清醒大鼠之解熱降溫作用機轉進行探討，期能有助於中藥之科學化。研究結果顯示，由側腦室給予puerarin (100mg/kg, intracerebroventricular injection; i.c.v.) 可引起室溫下 (24±1℃) 正常清醒大鼠體溫降低作用，且腹腔給予 puerarin (5-30mg/kg, intraperitoneal administration; i.p.) 可引起一具劑量依存性之體溫降低作用，並同步降低大鼠下視丘 serotonin (5-HT) 之濃度；此降溫作用會因側腦室給予 serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 200mg/10ml, i.c.v.) 或皮下給予5-HT1A 受體之拮抗劑 (-)-pindolol (0.05, 0.5mg/kg, subcutaneously injection; s.c.)所減弱，但可被皮下給予 5-HT1A 受體之致效劑 8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 0.05mg/kg; s.c.) 所加強。此外，puerarin 誘發之降溫作用亦會被5-HT2 受體之致效劑 (±)-2,5-dimethoxy-4-iodoamphetamine (DOI; 5, 10mg/10ml; i.c.v.; 0.5, 1mg/kg; i.p.)、quipazine (0.1, 1mg/kg; i.p.) 所拮抗，或為 5-HT2 受體之拮抗劑 pirenperone (0.2mg/kg; s.c.)、ketanserin (1mg/kg; i.p.) 所加強。由此可推知 puerarin 可能藉由降低下視丘 serotonin 之濃度，並作用於 postsynaptic serotonin 受體，致活 5-HT1A 受體及阻斷 5-HT2 受體，而達到降低體溫之作用。其次，puerarin (10,30mg/kg; i.p.) 對室溫下細菌內毒素 lipopolysaccharide (LPS; 100mg/kg; i.p.) 所誘發發燒之大鼠，具有明顯及劑量依存性之解熱作用；puerarin (100mg/10ml, i.c.v.; 10, 30mg/kg; i.p.) 對側腦室給予內生性致熱原 IL-1b (10ng/10ml) 誘發之發燒反應與下視丘 serotonin 濃度增加現象，亦具有抑制作用。此外，puerarin (10, 30mg/kg; i.p.) 可明顯抑制 NO donor (S-nitroso-N-acetylpenicillamine; SNAP, 10mg/10ml; i.c.v.)、NO releaser (sodium nitroprusside; SNP; 20mg/10ml; i.c.v.) 和 cGMP 之類似物 8-Bromo-cGMP (100mg/10ml) 及 PGE2 (100mg/10ml; i.c.v.) 或 cAMP 之類似物 8-Bromo-cAMP (40mg/10ml, intrahypothalamic injection; i.h.)等熱原媒介物質物所誘發之發燒反應。綜合以上結果，puerarin 具明顯之解熱降溫作用，其作用機轉可能是藉由抑制中樞 serotonin、nitric oxide 及 prostaglandin 等系統之活性所達成。; Puerarin is an isoflavone compound isolated from Pueraria lobata. The Puerariae radix has been used for antipyretic in Chinese. Puerarin, a beta-adrenergic receptor blocker, possesses anticonvulsive, antiarrhythmic and antihypertension effects. It also reduces 2,4-dinitrophenol-induced hyperthermia. However, the effects of puerarin on normal body temperature and pyrogenic fever are unknown. On this account, in the present study, experiments were carried out to assess the effects of puerarin on thermoregulatory responses in unanesthetized rats. Puerarin (100mg/10ml,i.c.v.;5-30mg/kg, i.p.) caused a dose-related fall in both colonic temperature and the 5-HT release in the hypothalamus at room temperature. The serotonin release in the hypothalamus was monitored with a microdialyzed probe is association with microdialysis-high perforemance liquid chromatography. Puerarin induced hypothermia was attenuated by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT; a serotonin neurotoxin, 200mg/10ml; i.c.v., one week ago), or (-)-pindolol (a 5-HTIA receptor/b adrenoceptor antagonist; 0.05, 0.5mg/kg; s.c.) but potentiated by (±)-8-hydroxydiopropylamino-teralin (8-OH-DPAT; a 5-HT1A receptor agonist; 0.05mg/kg; s.c.). In addition, the puerarin induced hypothermia was attenuated by (±)-2,5-dimethoxy-4-iodoamphetamine (DOI; 5-HT2 receptor agonist; 5, 10mg/10ml; i.c.v.; 0.5, 1mg/kg; i.p.) or quipazine (a 5-HT2 receptor agonist; 0.5, 1mg/kg; i.p.), but potentiated by ketanserin (5-HT2 receptor antagonist; 1mg/kg; i.p.) or pirenperone (5-HT2 receptor antagonist; 0.2mg/kg; s.c.). These results indicate that puerarin may act through 5-HT1A receptor activation or 5-HT2 receptor antagonism within the brain to induce its hypothermia. The fever induced by either lipopolysaccharide (LPS, 100mg/kg; i.p.) or interleukin-1b (IL-1b, 10ng/10ml; i.c.v.) was attenuated by treatment with puerarin (100mg/10ml, i.c.v.; 10, 30mg/kg, i.p.). Our microdialysis data revealed that puerarin (10, 30mg/kg; i.p.) reduces the increased 5-HT release in the hypothalamus and fever provoked by IL-1b injection. The hyperthermia induced by either S-nitroso-N-acetylpenicillamine (nitric oxide donor, 10mg/10ml; i.c.v.), sodium nitroprusside (NO releaser, 20mg/10ml; i.c.v.), 8-Bromo-
顯示於類別:	[中國藥學研究所(已停用)] 博碩士論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
88CMCH0049004.pdf		232Kb	Adobe PDF	1385	檢視/開啟

在CMUR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....