莉芙敏对去卵巢大鼠下丘脑视前区5-HT1AR和5-HT2AR表达的影响

摘要

Objective : To investigate regional changes in 5-hydroxytryptamine ( 5-HT) 1A receptors (5 -HT1AR) and 5-hydroxytryptamine (5-HT) 2A receptors (5-HT2AR) in the OVX rat preoptic area of hypothalamus after 1-4 weeks treatment with isopropanolic black cohosh extract-remifemin (ICR). and explore its potential mechanism of alleviating hot flushes during the peri -menopausal period. Methods:The rats were divided into f'our groups, ovariectomy (OVX) group,sham group,ovariectomy with estradiol valerate (E2) treatment (OVX+E2)group, and ovariectomy with ICR treatment (OVX +ICR) group. The sham group underwent a sham operation without ovariectomies.while the other three groups underwent bilateral ovariectomies under sterile conditions. All rats were given 2 weeks to recover after the operation, then each group was given a different treatment lasting 1 week , 2 weeks , 3 weeks and 4 weeks. The expression of 5-HTIAR and 5-HT2AR in the rat preoptic area of hypothalamus(POAH)were detected by immunohistochemistry. Results : ①After 1-4 weeks' treatment . the number of 5-HT1AR positive cells and the optical density ( OD) in POAH of OVX group significantly increased compared with that in the same period of sham group ; while the number of 5-HTIAR positive cells and the optical density in periventricular zone of OVX+ICR group and OVX+E2 group significantly decreased compared with that in the same period of OVX group.②After 1-4 weeks'treatment,the number of 5-HT2AR positive cells and the optical density (OD) in intermediate zone and lateral zone of OVX group significantly increased compared with that in the same period of sham group. The number of 5-HT2AR positive cells and the optical density (OD) in intermediate zone and lateral zone of OVX+ICR group and OVX+E2 group significantly increased compared with that in the same period of OVX group after 1 -2 weeks' treatment. While the result is reverse after 3 -4 weeks' treatment. Conclusions:Ovariectomized rats had increased expression of 5 -HT1AR and 5 -HT2AR.After treatment with remifemin or estradiol valerate.the expression of 5-HT1AR in POAH significantly decreased. While the expression of 5 -HT2AR in POAH decreased following an increased period.Regulating the expression of 5 -HT1AR and 5 -HT2AR in POAH may be one of the mechanisms of remifemin alleviating menopausal hot flush .%目的:观察去卵巢大鼠应用黑升麻异丙醇提取物--莉芙敏(ICR)治疗1-4周后,免疫组化方法检测5-羟色胺1A受体(5-HT1AR)和5-HT2AR在大鼠下丘脑视前区表达的变化情况,为莉芙敏缓解围绝经期潮热症状的机制研究提供形态学依据.方法:雌性大鼠分为假手术组(Sham组)、去卵巢组(OVX组)、OVX后戊酸雌二醇治疗(OVX+E2)组和OVX后ICR治疗(OVX+ICR)组,每组40只.所有大鼠术后恢复2周后,再用相应的药物分别治疗1,2,3,4周,麻醉,心脏灌注,取脑,制作冰冻切片.免疫组化法观察各组大鼠下丘脑视前区5-HT1AR和5-HT2AR的表达.结果:①OVX组1-4周时大鼠下丘脑视前区5-HT1AR阳性细胞数量和吸光度均较同期Sham组增加;ICR和戊酸E2治疗1-4周后,OVX+E2组和OVX+ICR组大鼠下丘脑视前区室周带表达5-HT1AR的阳性细胞数量和吸光度均较同期OVX组减少.②下丘脑视前区中间带和外侧区5-HT2AR阳性细胞数量和吸光度的变化:OVX组大鼠,1-4周均较同期Sham组增加;ICR和戊酸E2治疗1周和2周后,OVX+E组和OVX+ICR组较同期OVX组增加;治疗3周和4周后,OVX+E2组和OVX+ICR组均较同期OVX组减少.结论:5-HT1AR和5-HT2AR在去卵巢大鼠下丘脑视前区的表达量均增加;ICR和戊酸E2治疗后,5-HT1AR在大鼠下丘脑视前区的表达量减少,而5-HT2AR在下丘脑视前区的表达先增多后减少.ICR可能通过调节下丘脑视前区体温调节中枢的5-HT1AR和5-HT2AR的表达,以缓解围绝经期的潮热症状.