A study forthe effects of estrogen on actions ofendothelium-derived hyperpolarizing factor

雌激素对内皮源性超极化因子作用影响的研究

• 批准号: 11470342
• 负责人: SAKUMA Ichiro
• 金额: $ 9.34万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470342/
• 关键词: endothelium-derived hyperpolarizing factor; potassium channel; rat; mesenteric artery; resting membrane potential; estrogen; ovariectomy; connexin; カリウムチャネル; 腸間脈動脈

Endothelium-derived hyperpolarizing factor (EDHF) is released from endothelial cells and function to open reseitance vessels and have a pivotal role in the regulation of blood pressure and microcirculalion of organs.There are some candidates for EDHF, such as P450 metabolite, H_2O_2 and pottasium ion, and one of EDHFs is now thought to be electrical transmission of hypeipolarization of the endothelial cell membrane through gap junction. Estrogen is cardio- and vessel-protective and contributes to help women free from atherosclerosis and ischemic heart disease. The protective actions may arise, in part, from its effect on EDHF. Since gap junction consists of connexins and they are dramatically modulated by estrogen, we tried to investigate the nature of EDHF using estrogen as a clue. Middle-aged female rats was ovariectomized (OVX) or then estrogen-replaced (ERT), and compared with sham-operated ones (CON). The resting membrane potential of the endothelium-intact mesenteric artery of OVX was shallower than that of CON, and reversed in ERT. Acetylcholine-induced hypeipolarization and relaxation of the mesenteric artery were impaired in OVX and recovered in ERT. Immunostaining of connexin 43 using specific antibody revealed a confound decrease in connexin in OVX compared with CON and ERT. Western blotting of connexin 43 protein showed a decrease in the protein expression in OVX compared with the others. To further investigate the nature of EDHF we checked the presence of mRNAs of K channels and now started seeking the role of these channels in EDHF function.

内皮衍生超极化因子（endothelial -derived hyperpolarization factor， EDHF）由内皮细胞释放，具有打开阻力血管的功能，在调节血压和器官微循环中起关键作用。EDHF有几种候选物质，如P450代谢物、H_2O_2和钾离子，目前认为EDHF的一种是内皮细胞膜通过间隙连接的超极化电传递。雌激素对心脏和血管有保护作用，有助于帮助女性避免动脉粥样硬化和缺血性心脏病。这种保护作用可能部分来自于它对EDHF的作用。由于缝隙连接由连接蛋白组成，并且它们受到雌激素的显著调节，我们试图以雌激素为线索研究EDHF的性质。对中年雌性大鼠进行卵巢切除（OVX）或雌激素替代（ERT），并与假手术大鼠（CON）进行比较。OVX组内皮完整的肠系膜动脉静息膜电位较CON组浅，ERT组则相反。乙酰胆碱诱导的肠系膜动脉超极化和舒张在OVX中受损，在ERT中恢复。使用特异性抗体对连接蛋白43进行免疫染色，发现OVX中连接蛋白与CON和ERT相比明显减少。Western blotting结果显示，OVX细胞中连接蛋白43的表达明显低于其他细胞。为了进一步研究EDHF的性质，我们检查了K通道mrna的存在，现在开始寻找这些通道在EDHF功能中的作用。

项目成果

Ichiro Sakuma, et al.: "Hormone replacement therapy to protect health of elderly women"Geriatric Medicine. 38(2). 201-206 (2000)

佐久间一郎等人：“激素替代疗法保护老年妇女的健康”老年医学。

Ichiro Sakuma, Akira Kitabatake: "Hypertension in Climacterium"Therapy Today. 9 (8). 922-924 (2001)

Ichiro Sakuma、Akira Kitabatake：“更年期高血压”今日疗法。

Ichiro Sakuma, Akira Kitabatake: "Strategic approach for disease prevention from stand point of gender difference"J. Jap. Dis. Prev. Syst.. 7 (1). 149-151 (2001)

佐久间一郎、北竹彰：“从性别差异的角度来看疾病预防的战略方法”J.

佐久間一郎, 北畠 顕: "高齢女性の健康を守るホルモン補充療法"Geriatric Medicine. 38(2). 201-206 (2000)

Ichiro Sakuma，Akira Kitabatake：“保护老年妇女健康的激素替代疗法”38(2) (2000)。

佐久間一郎, 和田博司, 北畠 顕: "心血管病変とHRT"からだの科学. 219. 50-54 (2001)

Ichiro Sakuma、Hiroshi Wada、Akira Kitabatake：“心血管病变和 HRT”《身体科学》219. 50-54 (2001)。