香芩解热颗粒对内毒素致热家兔体温正负调节介质的作用研究
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摘要
目的:通过检测内毒素致热家兔下丘脑体温的正负反馈调节介质前列腺素2(PEG2)及精氨酸血管加压素(AVP)表达水平,探讨香芩解热颗粒对内毒素致热动物模型体温的正负调节介质的作用及机制。方法:40只新西兰兔,随机分为对照组,模型组,香芩解热颗粒低、高剂量组,每组10只。各组预防性灌胃给药后建立内毒素致热家兔模型,造模4h后处死动物取脑组织,应用酶联免疫法(ELISA)测定下丘脑中PEG2及AVP含量;应用实时荧光定量PCR技术测定下丘脑中PGE2受体EP1、EP4受体mRNA的相对表达量。结果:模型组家兔体温均显著高于对照组(P<0.05);与模型组比较,香芩解热颗粒高剂量组体温小于模型组(P<0.05)。ELISA结果显示:与对照组比较,模型组AVP含量显著上升、PGE2含量显著上升;与模型组比较,香芩解热颗粒低剂量组AVP含量显著上升;香芩解热颗粒低、高剂量组PGE2含量显著下降(P<0.05)。PCR结果显示:造模4h后,与对照组比较,模型组家兔下丘脑EP1 mRNA、EP4 mRNA相对表达量显著上升(P<0.05);与模型组比较,香芩解热颗粒低、高剂量组家兔下丘脑EP1 mRNA、EP4 mRNA相对表达量均显著下降(P<0.05),且香芩解热颗粒高剂量组的降低程度大于香芩解热颗粒低剂量组。结论:香芩解热颗粒对内毒素引起的发热有明显的抑制作用,其作用机制可能与促进体温的负调节介质AVP生成和释放、降低体温的正调节介质PGE2水平以及抑制PGE2受体EP1、EP4的表达有关。
Objective: To replicate the pyretic rabbits induced by endotoxin and to determine the expression levels of prostaglandin 2(PEG2) and arginine vasopressin(AVP), which are the regulatory mediators of positive and negative feedback of hypothalamic temperature in rabbits, and to discuss the function and mechanism of Xiangqin Jiere Granules on positive and negative mediators in body temperature in pyretic rabbits induced by endotoxin. Methods: Forty New Zealand rabbits were randomly divided into control group, model group, low and high dose group of Xiangqin Jiere Granules with 10 rats in each group. Pyretic rabbits induced by endotoxin were established after prophylactic intragastric administration, and they were sacrificed to obtain brain tissues 4 hours after the model was established. The contents of PEG2 and AVP in the hypothalamus were measured by enzyme-linked immunosorbent assay(ELISA); real-time fluorescent quantitative PCR was used for the relative expression levels of PGE2 receptor EP1 and receptor EP4 mRNA in the hypothalamus. Results: The body temperature of the rabbits in the model group was significantly higher than that of the control group(P<0.05). Compared with the model group, the body temperature T of the high-dose group of Xiangqin Jiere Granules was lower than that of the model group(P<0.05). ELISA results showed that compared with the control group, the AVP content in the model group increased significantly and the PGE2 content increased significantly; compared with the model group, the AVP content in the low-dose group increased significantly; the PGE2 content in the low-dose and high-dose groups decreased significantly(P<0.05). The results of PCR showed that compared with the control group, the relative expression of EP1 mRNA and EP4 mRNA in the hypothalamus of the rabbits in the model group increased significantly(P<0.05) after 4 hours of modeling. Compared with the model group, the relative expression of EP1 mRNA and EP4 mRNA in the hypothalamus of rabbits was significantly decreased in the low and high doses groups of Xiangqin Jiere Granules(P<0.05), and the decrease in the high-dose group was greater than that in the low-dose group. Conclusion: Xiangqin Jiere Granules can significantly inhibit the endotoxin-induced fever, and its mechanism may be related to the production and release of AVP which promotes the negative regulation of body temperature, the level of positive regulation mediator PGE2 which can lower body temperature, and the inhibition of the expression of PGE2 receptor EP1, EP4.
Objective: To replicate the pyretic rabbits induced by endotoxin and to determine the expression levels of prostaglandin 2(PEG2) and arginine vasopressin(AVP), which are the regulatory mediators of positive and negative feedback of hypothalamic temperature in rabbits, and to discuss the function and mechanism of Xiangqin Jiere Granules on positive and negative mediators in body temperature in pyretic rabbits induced by endotoxin. Methods: Forty New Zealand rabbits were randomly divided into control group, model group, low and high dose group of Xiangqin Jiere Granules with 10 rats in each group. Pyretic rabbits induced by endotoxin were established after prophylactic intragastric administration, and they were sacrificed to obtain brain tissues 4 hours after the model was established. The contents of PEG2 and AVP in the hypothalamus were measured by enzyme-linked immunosorbent assay(ELISA); real-time fluorescent quantitative PCR was used for the relative expression levels of PGE2 receptor EP1 and receptor EP4 mRNA in the hypothalamus. Results: The body temperature of the rabbits in the model group was significantly higher than that of the control group(P<0.05). Compared with the model group, the body temperature T of the high-dose group of Xiangqin Jiere Granules was lower than that of the model group(P<0.05). ELISA results showed that compared with the control group, the AVP content in the model group increased significantly and the PGE2 content increased significantly; compared with the model group, the AVP content in the low-dose group increased significantly; the PGE2 content in the low-dose and high-dose groups decreased significantly(P<0.05). The results of PCR showed that compared with the control group, the relative expression of EP1 mRNA and EP4 mRNA in the hypothalamus of the rabbits in the model group increased significantly(P<0.05) after 4 hours of modeling. Compared with the model group, the relative expression of EP1 mRNA and EP4 mRNA in the hypothalamus of rabbits was significantly decreased in the low and high doses groups of Xiangqin Jiere Granules(P<0.05), and the decrease in the high-dose group was greater than that in the low-dose group. Conclusion: Xiangqin Jiere Granules can significantly inhibit the endotoxin-induced fever, and its mechanism may be related to the production and release of AVP which promotes the negative regulation of body temperature, the level of positive regulation mediator PGE2 which can lower body temperature, and the inhibition of the expression of PGE2 receptor EP1, EP4.
引文
[1]林丽丽,汪受传.汪受传从祛邪安正辨证论治小儿发热.中华中医药杂志,2016,31(11):4556-4557
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[7]Chen X,Landgraf R,Pittman Q J.Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE2fever.American Journal of Physiology,1997,272(2):1664-1669
[8]焦平,钟振环,王海燕,等.小儿退热解毒颗粒对发热大鼠下丘脑中PGE2及cAMP含量的影响.中国中医急症,2007,16(7):842-843
[9]刘进娜,谢鸣.补中益气汤及其不同配伍对脾虚发热模型的退热作用比较.中华中医药杂志,2014,29(6):1814-1818
[2]聂坚,胡文敏,李刚,等.香芩解热颗粒对酵母致热大鼠的解热作用.中华中医药杂志,2017,32(10):4692-4695
[3]杨果杰,陈秀莲,邵萍,等.内毒素法兔发热动物模型及其标准化的研究.中国实验动物学报,2001,4:57-60
[4]李楚杰.发热时体温的正调节和负调节.中国病理生理杂志,1994(5):553-557
[5]杨惠玲.高级病理生理学.北京:科学出版社,1998:86-112
[6]霍海如,谭余庆,李晓芹,等.桂枝汤有效部位A对体温双向调节作用机理研究-对下丘脑和隔区AVP及下丘脑NT含量的影响.中国实验方剂学杂志,1999,5(1):11-13
[7]Chen X,Landgraf R,Pittman Q J.Differential ventral septal vasopressin release is associated with sexual dimorphism in PGE2fever.American Journal of Physiology,1997,272(2):1664-1669
[8]焦平,钟振环,王海燕,等.小儿退热解毒颗粒对发热大鼠下丘脑中PGE2及cAMP含量的影响.中国中医急症,2007,16(7):842-843
[9]刘进娜,谢鸣.补中益气汤及其不同配伍对脾虚发热模型的退热作用比较.中华中医药杂志,2014,29(6):1814-1818