A Study on Mechanisms of Regional Differences of Side Effects of Hormone Replacement Treatment (HRT)

激素替代治疗（HRT）副作用区域差异机制研究

• 批准号: 16406001
• 负责人: HAYASHI Toshio
• 金额: $ 8.32万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16406001/
• 关键词: Hormone Replacement Therapy; Postmenopausal Women; Comprehensive Geriatric Assessment; Single Nucleotide Polymorphism; Metabolic Syndrome; Atherosclerosis; 遺伝子解析

Total 1971 postmenopausal women participated the study during 3 years (China: Chengdu n=345, Kumming n=333, Korea: Seoul n=306, Nepal: Katmandu n=156, Iran: Teheran n=201, and Japan: Nagoya n=629). Hormone replacement therapy were applied for 32% of Korean participants, 4% of Japanese, however 0% to other country's peoples. Questionnaires revealed that Japanese. postmenopausal women hope stay indoors, rarely enjoy exercises and have fewer hobbies other than other Asian women. The mean age was 66.77±5.09 yrs, and mean years after menopause was 18.22±7.41 yrs. Compared with data reported, the mean levels of BMI, WC, systolic BP, diastolic BP, and TG tended to be higher.The prevalence of MetS diagnosed by IDF, NCEP ATPIII, CDS and JPN criteria were 37.34%, 27.31%, 23.29%, and 13.65%, respectively. IDF-MetS had the highest prevalence, whereas JPN-MetS had the lowest one. Although no significant changes of adipocytokines were found among different MetS groups, CDS MetS group tended to have … More the lowest levels of adiponectin, whereas JPN MetS group tended to have the highest levels of TNF alpha and IL-6.Adipocytokines may be the key factors link visceral adipose accumulation and atherosclerotic diseases, by playing harmful (eg.TNFalpha, IL-6) or protective (eg. adiponectin) roles. In our study, adiponectin levels were revealed to be significant higher in MetS groups than in normal groups. No significant differences were revealed between PMW with MetS and PMW with metabolic disorders.We are now analyzing the SNPs as above. Almost all genotype showed same pattern among asian countries, there may be some difference in the pattern of SNP of PAI-1, ER a, eNOS etc.Conclusively, IDF definition for MetS is the most sensitive one to metabolic disorders, whereas JPN and CDS definitions correlate better with CHD and changes of adipocytokines. The supplementation of different dcriteria with adipocytokines may give more meanings to the definition of metabolic syndrome. This study will cover the area of character, attitude and the specificity of asian postmenopausal women and may reveal the difference of atherosclerosis between Asian, American and European women, and may give us the clue of the taylor made therapy for the atherosclerotic diseases of Asian older female. Less

共有1971名绝经后妇女在3年内参加了研究（中国：成都n=345，昆明n=333，韩国：首尔n=306，尼泊尔：加德满都n=156，伊朗：德黑兰n=201，日本：名古屋n=629）。32%的韩国参与者接受了激素替代疗法，4%的日本参与者接受了激素替代疗法，而其他国家的参与者则为0%。日本人透露，绝经后的妇女希望呆在室内，很少喜欢锻炼，也没有其他亚洲妇女的爱好。平均年龄为66.77±5.09岁，平均绝经年限为18.22±7.41岁，BMI、WC、收缩压、舒张压和甘油三酯水平均高于文献报道，按IDF、NCEP ATP Ⅲ、CDS和JPN标准诊断的代谢综合征患病率分别为37.34%、27.31%、23.29%和13.65%。分别IDF-MetS患病率最高，JPN-MetS患病率最低。虽然不同MetS组间脂肪细胞因子无明显变化，但CDS MetS组有增加脂肪细胞因子的趋势。 ...更多信息 脂联素水平最低，而日本MetS组TNF α和IL-6水平最高。脂肪细胞因子可能是内脏脂肪堆积和动脉粥样硬化疾病之间的关键因素，通过发挥有害（如TNF α，IL-6）或保护（如TNF α，IL-6）作用。脂联素）的作用。在我们的研究中，脂联素水平被发现是显着高于代谢综合征组比正常组。PMW合并MetS与PMW合并代谢紊乱之间无显著性差异，我们现在分析SNPs如上所述。亚洲国家间几乎所有基因型的分布模式一致，派-1、ER α、eNOS等基因型的SNP分布可能存在一定差异。结论：IDF对代谢综合征的定义最敏感，而JPN和CDS定义与CHD和脂肪细胞因子变化的相关性更好。补充脂肪细胞因子的不同诊断标准可能会使代谢综合征的定义更有意义。本研究将涵盖亚洲绝经后妇女的性格、态度和特殊性，揭示亚洲、美国和欧洲妇女动脉粥样硬化的差异，并为亚洲老年女性动脉粥样硬化性疾病的泰勒疗法提供线索。少

项目成果

Strategy for treating elderly Japanese with hypercholesterolemia

日本老年人高胆固醇血症的治疗策略

• 发表时间: 2004
• 期刊: Geriatrics Gerontology International 4巻・2号
• 作者: Horiuchi H;Matsuzawa Y;Hayashi T;Yamane K;Egusa G;Kita T;他11名
• 通讯作者: 他11名

Selective iNOS inhibitor, ONO1714 successfully retards the development of high-cholesterol diet induced atherosclerosis by novel mechanism

• DOI: 10.1016/j.atherosclerosis.2005.10.023
• 发表时间: 2006-08-01
• 期刊: ATHEROSCLEROSIS
• 影响因子: 5.3
• 作者: Hayashi, Toshio;Matsui-Hirai, Hisako;Iguchi, Akihisa
• 通讯作者: Iguchi, Akihisa

Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism

• DOI: 10.1073/pnas.0603918103
• 发表时间: 2006-07-05
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Hayashi, Toshio;Esaki, Teiji;Chaudhuri, Gautam
• 通讯作者: Chaudhuri, Gautam

酸化ストレスと心血管病(執筆項目 酸化ストレスとエストロゲン)

氧化应激与心血管疾病（书面项目：氧化应激与雌激素）

• 发表时间: 2007
• 作者: 横山 光宏;藤田 敏郎 編集;林 登志雄;井口昭久 著
• 通讯作者: 井口昭久 著

17beta-estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase by High Glucose : Relevance to Postmenopausal Diabetic Cardiovascular Disease.

17β-雌二醇拮抗高血糖引起的内皮一氧化氮合酶和 GTP 环水解酶的下调：与绝经后糖尿病心血管疾病的相关性。

• 发表时间: 2007
• 期刊: J Pharmacol Exp Ther. 320
• 作者: Miyazaki-Akita A;Hayashi T;Ding QF;Shiraishi H;Nomura T;Hattori Y;Iguchi A
• 通讯作者: Iguchi A