慢性间歇性低压低氧通过PI3K依赖的eNOS活化增强大鼠胸主动脉舒张

doi:10.6040/j.issn.1671-7554.0.2015.513

山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (2): 11-15.doi: 10.6040/j.issn.1671-7554.0.2015.513

慢性间歇性低压低氧通过PI3K依赖的eNOS活化增强大鼠胸主动脉舒张

王立轩^1*,张璐^2*,许新²,李思雪²,刘敏³,王亚萍³,马慧娟^3,4

河北医科大学 1. 组织胚胎学教研室;2. 2011级七年制临床医学班;3. 生理学教研室;4. 河北省实验动物重点实验室, 河北石家庄 050017

收稿日期:2015-05-24 出版日期:2016-02-10 发布日期:2016-02-10
通讯作者: 马慧娟. E-mail: ankang006@126.com*共同第一作者 E-mail:ankang006@126.com
基金资助:
国家自然科学基金(31100832);河北省自然科学基金(C2013206183);国家级大学生创新实验(201310089004)

Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats

WANG Lixuan^1*, ZHANG Lu^2*, XU Xin², LI Sixue², LIU Min³, WANG Yaping³, MA Huijuan^3,4

1. Department of Histology and Embryology;
2. Class of Seven-year Clinical Medicine Registered in 2011;
3. Department of Physiology;
4. Hebei Key Laboratory of Laboratory Animal Science, Hebei Medical University, Shijiazhuang 050017, Hebei, China

Received:2015-05-24 Online:2016-02-10 Published:2016-02-10

摘要/Abstract

摘要： 目的探讨慢性间歇性低压低氧(CIHH)对大鼠胸主动脉环舒张活动的影响及其一氧化氮相关机制。方法成年雄性SD大鼠80只,随机分为对照组(CN组)和慢性间歇性低压低氧组(CIHH组),每组40只。CIHH组给予模拟海拔5 000 m(P_B=404 mmHg,P_O2=84 mmHg)的低压低氧处理,6 h/d,共28 d。对照组处于常压常氧环境,平行饲养。应用离体血管环灌流记录胸主动脉的舒缩活动;采用Western blotting法检测胸主动脉组织中eNOS和PI3K的表达水平。结果与CN组相比,CIHH组乙酰胆碱引起的胸主动脉舒张明显增强(P<0.05),胸主动脉组织中eNOS的表达增多(P<0.05);MEK阻断剂PD98059孵育,对CN组和CIHH组无影响;PI3K阻断剂LY294002孵育,可阻断CIHH组胸主动脉舒张增强和eNOS表达增多(P<0.05);且CIHH组胸主动脉组织中PI3K的表达升高(P<0.05)。结论 CIHH处理可通过PI3K途径活化血管内皮eNOS,增强乙酰胆碱诱导的大鼠胸主动脉舒张。

关键词: 慢性间歇性低压低氧, 舒张血管, 抗高血压, eNOS, PI3K

Abstract: Objective To investigate the effects of chronic intermittent hypobaric hypoxia(CIHH)on the vasodilatation in isolated thoracic aorta and the nitric oxide related mechanism in rats. Methods A total of 80 male adult Sprague-Dawley rats were randomly divided into two groups: control group(CN, n=40)and CIHH group(CIHH, n=40). The rats in CIHH group were exposed to hypoxia simulating at 5000-meter altitude in a hypobaric chamber(P_B=404 mmHg, P_O2=84 mmHg)for 28 days, 6 hours each day. The rats in CN group lived in a normoxic environment for the same period. The vasodilatation of thoracic aorta was recorded by using organ bath technique. The protein expressions of eNOS and PI3K were measured by using Western blotting. Results CIHH could remarkably augment the acetylcholine(ACh)-induced vasodilatation of thoracic aorta(P<0.05)and increase the expression of eNOS in thoracic aorta tissues(P<0.05). Incubation with MEK inhibitor PD98059 did not affect the effects of CIHH on thoracic aorta. Incubation of PI3K inhibitor LY294002 blocked the effects of CIHH(P<0.05). Furthermore, CIHH treatment could improve the expression of PI3K in thoracic aorta tissue(P<0.05). Conclusion CIHH treatment enhances Ach-induced vasodilatation of thoracic aorta by activating eNOS via PI3K pathway.

Key words: PI3K, Anti-hypertension, Vasodilatation, Chronic intermittent hypobaric hypoxia, eNOS

中图分类号:

Q463

王立轩,张璐,许新,李思雪,刘敏,王亚萍,马慧娟. 慢性间歇性低压低氧通过PI3K依赖的eNOS活化增强大鼠胸主动脉舒张[J]. 山东大学学报（医学版）, 2016, 54(2): 11-15.

WANG Lixuan, ZHANG Lu, XU Xin, LI Sixue, LIU Min, WANG Yaping, MA Huijuan. Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 11-15.

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慢性间歇性低压低氧通过PI3K依赖的eNOS活化增强大鼠胸主动脉舒张

Chronic intermittent hypobaric hypoxia enhances the vasodilatation of thoracic aorta via PI3K-dependent eNOS activation in rats

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