Basic and clinical investigation of the mechanism in the aldosterone regulation by the sympathetic system

交感神经系统调节醛固酮机制的基础与临床研究

• 批准号: 22780284
• 负责人: HORI Yasutomo
• 金额: $ 2.5万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22780284/
• 关键词: 内科; 心臓病; アルドステロン; 線維化

Our objectivewas to investigate the effectsof doxycycline, a matrix metalloproteinase(MMP) inhibitor(MMPi) on ss-agonist-induced myocardial fibrosis and MMP expression. Rats were divided into 3groups : control, Isoproterenol(ISO), and Isoproterenolwith doxycycline(ISO+DOX). Compared to the control, ISO induced the myocardial hypertrophyand cardiacfibrosis, but were attenuated by co-treatment with DOX. MMP-2 activity alsoincreased in the ISO treatment, but decreased by co-treatment with DOX. Similarly, immunoblotting showedsignificant increaseinMMP-2levelin the ISO, and decreased levels in the DOX co-treatment. Ourresults suggest that the enhanced expression of MMP-2plays a prominent role inpromoting myocardial fibrosis inβ-agonist signaling pathway, and that MMP-inhibiting compoundsmay attenuate myocardial fibrosis.

我们的目的是研究多西环素，一种基质金属蛋白酶（MMP）抑制剂（MMPi）对β受体激动剂诱导的心肌纤维化和MMP表达的影响。将大鼠分为对照组、异丙肾上腺素组（ISO组）和异丙肾上腺素+多西环素组（ISO+DOX组）。与对照组相比，ISO可引起心肌肥厚和心肌纤维化，DOX可减轻ISO的心肌肥厚和心肌纤维化。MMP-2活性在ISO处理中也增加，但在DOX的共同处理中降低。同样，免疫印迹显示ISO组MMP-2水平显著升高，DOX联合治疗组MMP-2水平降低。结果提示，MMP-2的表达增强在β-激动剂信号通路中起着促进心肌纤维化的重要作用，MMP抑制剂可减轻心肌纤维化。

项目成果

心筋線維芽細胞における交感神経受容体を介したアルドステロン分泌機序の解明

阐明心脏成纤维细胞交感神经受体介导的醛固酮分泌机制

• 发表时间: 2011
• 作者: 藤栄大輔;堀泰智
• 通讯作者: 堀泰智

Spironolactone Decreases Isoproterenol-Induced Ventricular Fibrosis and Matrix Metalloproteinase-2 in Rats

• DOI: 10.1248/bpb.34.61
• 发表时间: 2011-01-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Hori, Yasutomo;Yoshioka, Kazuki;Higuchi, Sei-ichi
• 通讯作者: Higuchi, Sei-ichi