BACKGROUND： It has been shown that interleukin-1β（IL-1β） can induce fever by activating vascular endothelial cells and macrophages of the supraoptic crest to generate prostaglandin E2, which binds with receptors ...BACKGROUND： It has been shown that interleukin-1β（IL-1β） can induce fever by activating vascular endothelial cells and macrophages of the supraoptic crest to generate prostaglandin E2, which binds with receptors of the thermo-sensitive hypothalamic neurons. Lonicera japonica is one of the medicinal plants used widely in Asia for its antipyretic properties. However, these mechanisms have not yet been intensively studied. OBJECTIVE： To investigate the antipyretic effect and mechanisms of Lonicera japonica on IL-1β- induced febrile New Zealand rabbits by observing expression changes of E-type prostaglandin receptor-3 （EP3） mRNA in the preoptic anterior hypothalamus （POAH）. DESIGN： A randomized controlled study. SETTING： Electrophysiological Laboratory at the Department of Pathophysiology, Medical College of Jinan University; Department of Orthopaedics, First Hospital Affiliated to Medical College of Jinan University. MATERIALS： The experiment was performed from April to December 2005, using a total of 32 New Zealand white rabbits of both sexes, weighing 1.5 2.0 kg. All the animal experiments were performed according to the internationally accepted ethical guidelines. Lonicera japonica injection was purchased from Huanghe pharmaceutical factory of Xi＇an, China. IL-1βwas purchased from Sigma, USA. METHODS： A total of 32 rabbits were divided randomly into four groups： ① Normal saline （NS） control group;② Lonicerajaponica treatment group; ③ IL-1βtreatment group; and ④Lonicerajaponica plus IL-1βtreatment group. In the first 3 groups, the rabbits were given separate intravenous （i.v.） injections of l mL NS, l mL Lonicera japonica, and 100 ng IL-l β （dissolved in 0.9% NS without pyrogen）. In the Lonicerajaponica plus IL-1βgroup each rabbit was given i.v. injections of l mL NS and, 30 minutes later, 100 ng IL-1 β. MAIN OUTCOME MEASURES： Colonic temperature of each rabbit was measured at 0, 10, 20, 30, 40, 50, 60, and 70 minutes after injection and the maximum temperature rise （ A T） and the temperature response index after l hour （TRII） was calculated. Subsequently, in situ hybridization （ISH） was done with an ISH kit, EP3 mRNA expression in the POAH of all groups was measured （number of positive cells and average gray scale value）. RESULTS： A total of 32 rabbits were included in the result analysis, without any loss, （i） A T and TRII： there was no significant difference between the Lonicera japonica group and NS group （P 〉 0.05）. The IL-1β group was significantly greater compared to NS group （P 〈 0.01）. The Lonicera japonica plus IL-1β group was significantly less than the IL-1β group （P 〈 0.05）. ② In the NS and Lonicera japonica groups, the EP3 mRNA expression was negative （no coloration） or only weakly positive （only a few brown yellow particles in the cytoplasm cells could not be identified）. The number of positive cells and the average gray scale value were not significantly different between the two groups （P 〉 0.05）. In the IL-1β group, the number of positive cells was remarkably higher and the average gray scale value was lower than the NS group （P 〈 0.0 l）. In the Lonicera japonica plus IL-1β group, the number of positive cells was significantly less than the IL-1β group （P 〈 0.05）. However, the average gray scale value was greater than the IL-1β group （P 〈 0.05）. CONCLUSION： Lonicera japonica has obvious antipyretic effects on IL-1β-induced febrile rabbits and acts by inhibiting expression of EP3 mRNA in the POAH.展开更多
基金Grants from the National Natural Science Foundation of China, No. 39600061National Administration of Traditional Chinese Medicine, No.2003LHR13+3 种基金Medical Science Foundation of Guangdong Province, No. A2004327, A2006334the Natural Science Foundation of Guangdong, No. 04010443, 06105246 Administration Bureau of Traditional Chinese Medicine of Guangdong Province, No.1040074Technology Bureau of Guangzhou, No. 2007J1-C0041
文摘BACKGROUND： It has been shown that interleukin-1β（IL-1β） can induce fever by activating vascular endothelial cells and macrophages of the supraoptic crest to generate prostaglandin E2, which binds with receptors of the thermo-sensitive hypothalamic neurons. Lonicera japonica is one of the medicinal plants used widely in Asia for its antipyretic properties. However, these mechanisms have not yet been intensively studied. OBJECTIVE： To investigate the antipyretic effect and mechanisms of Lonicera japonica on IL-1β- induced febrile New Zealand rabbits by observing expression changes of E-type prostaglandin receptor-3 （EP3） mRNA in the preoptic anterior hypothalamus （POAH）. DESIGN： A randomized controlled study. SETTING： Electrophysiological Laboratory at the Department of Pathophysiology, Medical College of Jinan University; Department of Orthopaedics, First Hospital Affiliated to Medical College of Jinan University. MATERIALS： The experiment was performed from April to December 2005, using a total of 32 New Zealand white rabbits of both sexes, weighing 1.5 2.0 kg. All the animal experiments were performed according to the internationally accepted ethical guidelines. Lonicera japonica injection was purchased from Huanghe pharmaceutical factory of Xi＇an, China. IL-1βwas purchased from Sigma, USA. METHODS： A total of 32 rabbits were divided randomly into four groups： ① Normal saline （NS） control group;② Lonicerajaponica treatment group; ③ IL-1βtreatment group; and ④Lonicerajaponica plus IL-1βtreatment group. In the first 3 groups, the rabbits were given separate intravenous （i.v.） injections of l mL NS, l mL Lonicera japonica, and 100 ng IL-l β （dissolved in 0.9% NS without pyrogen）. In the Lonicerajaponica plus IL-1βgroup each rabbit was given i.v. injections of l mL NS and, 30 minutes later, 100 ng IL-1 β. MAIN OUTCOME MEASURES： Colonic temperature of each rabbit was measured at 0, 10, 20, 30, 40, 50, 60, and 70 minutes after injection and the maximum temperature rise （ A T） and the temperature response index after l hour （TRII） was calculated. Subsequently, in situ hybridization （ISH） was done with an ISH kit, EP3 mRNA expression in the POAH of all groups was measured （number of positive cells and average gray scale value）. RESULTS： A total of 32 rabbits were included in the result analysis, without any loss, （i） A T and TRII： there was no significant difference between the Lonicera japonica group and NS group （P 〉 0.05）. The IL-1β group was significantly greater compared to NS group （P 〈 0.01）. The Lonicera japonica plus IL-1β group was significantly less than the IL-1β group （P 〈 0.05）. ② In the NS and Lonicera japonica groups, the EP3 mRNA expression was negative （no coloration） or only weakly positive （only a few brown yellow particles in the cytoplasm cells could not be identified）. The number of positive cells and the average gray scale value were not significantly different between the two groups （P 〉 0.05）. In the IL-1β group, the number of positive cells was remarkably higher and the average gray scale value was lower than the NS group （P 〈 0.0 l）. In the Lonicera japonica plus IL-1β group, the number of positive cells was significantly less than the IL-1β group （P 〈 0.05）. However, the average gray scale value was greater than the IL-1β group （P 〈 0.05）. CONCLUSION： Lonicera japonica has obvious antipyretic effects on IL-1β-induced febrile rabbits and acts by inhibiting expression of EP3 mRNA in the POAH.
