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Genomic characteristics of pulmonary circulation in high-altitude living animal

高海拔活体动物肺循环基因组特征

基本信息

批准号：
16406026
负责人：
ISHIZAKI Takeshi
金额：
$ 8.06万
依托单位：
University of Fukui
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-16406026/
关键词：
Yak Pulmonary Circulation eNOS DDAH ADMA ET-1 低酸素適応高地適応極限高地生息動物ナキウサギ HIF1α ET1

项目摘要

We investigated the pulmonary characteristics of Yak, a high-altitude adapted animal that is resistant to hypoxia-induced pulmonary hypertension, cor pulmonale in terms of hypoxia-responsible genomic products such as eNOS, DDAH (dimethylarginine dimethylaminohydrolase), ADMA (asymmetrically methylated Arginine) and ET-1.Results;1. The protein expression of eNOS, and protein expression and activity of DDAH in yak's lung tissue were more elevated than that of control cow. However, the degree of protein expression of DDAH in the Kidney was the same in both animals.2. The plasma level of ADMA was 5-times higher in Yak compared to that of cow. Among cow groups, high-altitude living one has 4-times high ADMA level compared to that of low-altitude living one.3. The plasma ET-1 level was higher in Yak than in cow.These results suggest that wild yak's lung has augmented eNOS protein and augmented DDAH activity compared to cow. On the contrary, the animal has elevated plasma ADMA and ET-1 suggesting that the balance of vasodilators and vasoconstrictors are up-regulated. Although we did not assess transpulmonary difference of plasma ADMA and ET-1, it appears that Yak's lung preferentially expressed protective NO mechanism(s) which may result the relatively low pulmonary arterial pressure despite of high-altitude. It may induce a good suggestion from the animal study if think about hypoxic-air induced pulmonary hypertension and chronic respiratory failure in clinical medicine in terms of pathogenesis and treatment strategy.

本研究从缺氧相关基因产物eNOS、DDAH（dimethylarginine dimethylaminohydrolase）、ADMA（asymmetrically methylated Arginine）和ET-1等方面，探讨了高原适应性动物牦牛（hypoxia induced pulmonary hypertension，肺心病）的肺特性。牦牛肺组织eNOS蛋白表达、DDAH蛋白表达及DDAH活性均高于对照组。然而，DDAH在肾脏中的蛋白表达程度在两种动物中是相同的.牦牛血浆中ADMA水平比母牛高5倍。在奶牛群体中，高海拔生活奶牛的ADMA水平是低海拔生活奶牛的4倍.牦牛血浆ET-1水平高于普通牛，表明牦牛肺组织中eNOS蛋白表达和DDAH活性均高于普通牛。相反，该动物具有升高的血浆ADMA和ET-1，表明血管扩张剂和血管收缩剂的平衡被上调。虽然我们没有评估血浆ADMA和ET-1的跨肺差异，但似乎牦牛肺优先表达保护性NO机制，这可能导致尽管在高海拔地区，肺动脉压仍相对较低。从缺氧性肺动脉高压和慢性呼吸衰竭的发病机制和治疗策略方面对临床医学进行思考，可以从动物实验中得到有益的启示。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Current opinion低酸素と肺高血圧肺血管リモデリングを中心に

当前观点缺氧与肺动脉高压，重点关注肺血管重塑

DOI：
发表时间：
2007
期刊：
呼吸と循環 55
影响因子：
0
作者：
水野史朗;石崎武志
通讯作者：
石崎武志

低酸素性肺血管収縮

缺氧性肺血管收缩

DOI：
发表时间：
2006
期刊：
Annual Review 呼吸器
影响因子：
0
作者：
Saito M;Murata T;Watanabe K;Kawakami K;Suzuki M;Koji T;Puri RK;Kitazato K;Kobayashi N.;石崎武志
通讯作者：
石崎武志

Hypoxia-induced proliferation of human pulmonary arterial smooth muscle cell is involved in the suppression of cyclin-dependent kinase inhibitors, P21, P27 and P53.

缺氧诱导的人肺动脉平滑肌细胞增殖参与细胞周期蛋白依赖性激酶抑制剂 P21、P27 和 P53 的抑制。

DOI：
发表时间：
2006
期刊：
High Altitude Medicine and Biology Advanced Research Workshop Abstract book
影响因子：
0
作者：
Ishizaki T;Mizuno S;Kadowaki M;Uesaka D;Umeda Y;Morikawa M;Nakanishi M;Demura Y;Ameshima S
通讯作者：
Ameshima S

Current opinion 低酸素と肺高血圧肺血管リモデリングを中心に

当前观点缺氧与肺动脉高压，重点关注肺血管重塑