下丘脑孤啡肽参与电针调整去卵巢大鼠LH异常释放的神经内分泌机制

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,下丘脑孤啡肽参与电针调整去卵巢大鼠,LH,异常释放的神经内分泌机制,OFQ,对下丘脑,GnRH,和垂体,LH,释放的药理作用,（,3-1,）,孤啡肽（,OFQ,）,1995,年 下丘脑,孤儿受体,(,ORL1,),内源性配体,EOP,家族新成员，结构的同源性,痛觉的调制,多种生理功能活动,神经内分泌？,1998,PRL GH,研究背景,下丘脑,卵巢,垂体,GnRH,FSH,LH,E,2,P,HPOA,OFQ,及其受体分布,GnRH,调控部位,（,MBH ),MPO,（内侧视前区）,VMH,（腹内侧核）,ARC,（弓状核）,下丘脑,OFQ,与,GnRH,释放的调节有关系吗？,EOP,系统的比较,1998,年电生理膜片钳,临床疗效和动物实验,针灸和血,b-,内啡肽,围绝经期妇女雌激素替代治疗,电针调整去卵巢大鼠,HPOA,异常功能,问题,OFQ?GnRH-LH-E2,研究方法,实验动物 去卵巢大鼠,实验方法,icv injection,in vitro,incubation,RIA,ICC,RT-PCR,Western blot,The dose response curves,for the e,ffect of OFQ on plasma LH levels of OVX rats,(,b,P0.05 vs control),实验分组,Control,组 （,ACSF,，,10,l,icv,）,OFQ,组,(20nmolOFQ,，,10,l,icv),NC13+OFQ,组,(20nmol NC13+20nmolOFQ,icv),NC13,组,(20nmol NC13,，,10,l,icv),OFQ,ORL1,LH,ORL1,受体的选择性受体拮抗剂,Nphe1NC(1-13)NH2,（,NC13,）,?,Effect of pretreatment with NC13 on the decrease of plasma LH level induced by OFQ,(,b,P0.05 vs control),M:Marker A:hippocampus B:pituitary C:hypothalamus,RT-PCR analysis for the expression of ORL1 receptor,问题,OFQ,对垂体,LH,释放是否直接作用？,Effect of OFQ on the LH release from pituitary fragments,in vitro,Western blot analysis for the expression of ORL1 receptor,A,hypothalamus,B,pituitary,C,hippocampus,The dose response curves for the effect of OFQ on GnRH release in POA of hypothalamus in PPP,OFQ,对垂体,LH,释放,（间接作用）,是否通过,GnRH,？,OFQ GnRH,OFQ,LH,40min,2h,OFQ,LH,?,GnRH,直接观察,OFQ,抑制,LH,分泌过程中,GnRH,的变化,GnRH,神经元在脑内的分布,The different subtypes of GnRH-IR neurons(800,),A13:spins subtype B13:smooth subtype,Effect of OFQ on the number of GnRH-IR,neurons of OVX rats,（,b,P0.05 vs control,）,大鼠下丘脑区冠状切面概观（,10,）,下丘脑神经解剖和正中隆起,GnRH,阳性纤维,Effect of NC13 and OFQ on GnRH-IR fibers in ME (800,),The relative density analysis for GnRH-IR fibers,in ME,hypothalamus,(,b,P0.05 vs control),Co-localization of ORL1 mRNA in GnRH-IR neurons in rat hypothalamus.(ORL1 green;GnRH red and double labeled cells yellow),OFQ has no significant effect on the release of NE and DA from medial basal hypothalamus of rats(HPLC),国外研究,OFQ,可抑制神经细胞,Glu,的释放,（,in vitro,and,in vivo,),Glu,是调节,GnRH,释放兴奋性神经递质（,NMDA and KA),调控,GnRH,释放的因素,(+NE,DA,Glu)(-NPY?),NMDA,受体的选择性受体拮抗剂,MK-801,（,0.2mg/kg,sc,）,实验分组,Control,组 （,ACSF,，,icv,）,OFQ,组,(200nmolOFQ,，,icv),MK801+OFQ,组,(0.2mg/kg,sc,+,200nmolOFQ,icv),MK801,组,(0.2mg/kg,sc),NMDA,Effect of pretreatment with MK801 on the decrease of,plasma LH levels induced by OFQ,(,b,P0.05 vs control.,e,P0.05 vs OFQ group),The dose response study for the effect of NC13 on plasma LH levels of OVX rats,(,b,P0.05 vs control),小 结,下丘脑,OFQ,可能通过,ORL1,受体介导抑制,GnRH,的释放，从而减少垂体,LH,的分泌，使血,LH,水平降低。,NMDA,受体也可能部分介导了该作用。,提示,OFQ,可能参与了对,GnRH,和,LH,释放的生理调节作用，下丘脑可能存在,OFQ-Glu-GnRH,神经调节通路。,思考？,OFQ,可抑制,GnRH,和,LH,的释放的,药理和生理作用（,OFQ,和,NC13,有潜在的治疗作用）。,OFQ,及其受体,ORL1,可能为调整更年期综合症和性早熟神经内分泌异常提供等新的药物治疗靶点,。,（丹参酮）,下丘脑,OFQmRNA,及其蛋白水平可以作为筛选调节,GnRH,分泌中西药物的探针,。,Thank you,