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目的探讨雌性大鼠育龄期体内高水平17-β雌二醇(17-βE2)或孕酮(P)对其围绝经期及绝经后血压的影响,并观察血管紧张素Ⅱ-1型受体(AT1R)的变化。方法间情期切除大鼠双侧卵巢,利用17-β E_2和P建立人工动情周期模型,共分为3组:高剂量雌激素加低剂量孕激素组(HELP)、高剂量孕激素加低剂量雌激素组(HPLE)和卵巢切除组(OVX)。经按周期给予17-β E_2和P(8周)、递减剂量(5周)和停止给予(6周)依次模拟自然状态下的育龄期、围绝经期与绝经期,监测血压、血清E2、P、腹主动脉AT1R蛋白及其mRNA的表达水平。结果与OVX组比较,HELP组与HPLE组增加各模拟期的收缩压(P<0.05),HELP组明显升高围绝经模拟期与绝经模拟期的舒张压(P<0.05),并增加育龄模拟期和围绝经模拟期AT1R蛋白及其mRNA的表达(P<0.05);AT1R蛋白表达水平与血清E_2、SBP呈正相关(P<0.01)。结论育龄期体内高水平的E2能升高大鼠围绝经期及绝经后血压,且SBP的升高伴随腹主动脉中AT1R蛋白的高表达。
Objective To investigate the effect of high level of 17-β estradiol (17-βE2) or progesterone (P) on perimenopausal and postmenopausal women’s blood pressure during childbearing age in female rats and to observe the effect of angiotensin Ⅱ-1 receptor (AT1R) changes. Methods The bilateral ovaries were excised from the rats during the period of sentiment. The model of artificial estrous cycle was established by 17-βE_2 and P, and divided into three groups: high dose estrogen plus low dose progesterone (HELP), high dose progesterone plus low Dose estrogen group (HPLE) and ovariectomy group (OVX). Periodic delivery of 17-β E 2 and P (8 weeks), decreasing doses (5 weeks), and cessation of administration (6 weeks) were used to simulate childbearing age, perimenopause and menopause, monitoring blood pressure, serum E2, P, AT1R protein and mRNA expression in abdominal aorta. Results Compared with OVX group, HELP group and HPLE group increased systolic pressure at each simulation period (P <0.05), and HELP group significantly increased diastolic pressure (P <0.05) during menopausal and postmenopausal simulations and increased reproductive age The expression of AT1R protein and its mRNA in period and perimenopausal simulation period (P <0.05). The expression of AT1R protein was positively correlated with serum E_2 and SBP (P <0.01). CONCLUSION: High E2 levels in childbearing age can increase perimenopausal and postmenopausal BP, and elevated SBP is associated with high AT1R expression in the abdominal aorta.