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肺动脉胰岛素敏感性减弱在低氧性肺动脉高压发生中的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第3期
页码:
296-300
栏目:
基础研究
出版日期:
2013-06-25

文章信息/Info

Title:
Decreased insulin sensitivity of pulmonary artery contributes to development of hypoxic pulmonary hypertension
作者:
范 芳1; 王 浩1; 石曌玲1; 李 浩2; 李 娟3; 张海锋2; 孙 新1
(第四军医大学：1.西京医院儿科，2.教学实验中心，3.生理学教研室，陕西 西安 710032)
Author(s):
FAN Fang1;  WANG Hao1;  SHI Zhaoling1;  LI Hao2;  LI Juan3;  ZHANG Hai feng2;  SUN Xin1
(1.Department of Pediatrics, Xijing Hospital, 2.Experiment Teaching Center, 3.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
血管胰岛素抵抗; 低氧性肺动脉高压; 吡格列酮; 大鼠
Keywords:
vascular insulin resistance;  hypoxic pulmonary hypertension;  pioglitazone;  rat
分类号:
R543.2
DOI:
-
文献标识码:
A
摘要:
目的:观察低氧性肺动脉高压（HPH）时，肺动脉胰岛素敏感性的变化以及应用吡格列酮 (PIO) 不同时期处理对HPH的影响。探讨肺血管脉胰岛素抵抗（IR）在HPH发病中的作用及其机制。方法:将28只雄性SD大鼠随机分为正常对照组、HPH组、HPH 1周+PIO组及HPH 3周+PIO组，每组7只。后3组大鼠以低压低氧法建立HPH模型，每天低氧8 h，共4周。HPH 1周+PIO组和HPH 3周+PIO组的大鼠分别于低氧1周后及低氧3周后，开始每日低氧前给予PIO(10 mg/kg)灌胃，共1周。低氧结束后，用血糖仪检测空腹血糖（FBG）、ELISA方法检测空腹血清胰岛素(FSI)，计算胰岛素抵抗指数(IRI)，右心导管法测定平均肺动脉压（mPAP）、平均右心室压（mRVP），右心指数(RVI)。经HE染色后观察肺小动脉显微结构的改变。各组动物再取左、右肺外肺动脉干，采用离体血管灌流实验，观察胰岛素对苯肾上腺素(PE)预收缩后各组大鼠肺动脉舒张功能的影响。结果:与对照组相比，HPH组大鼠的FBG、FSI、IRI、mPAP、mRVP及RVI均显著增高(P<0.05)；肺动脉平滑肌及弹力纤维层增生，管壁增厚，管腔狭窄；胰岛素诱导的肺动脉舒张功能显著减弱（P<0.05）。与HPH组相比，HPH 1周+PIO组大鼠的FBG、FSI、IRI、mPAP、mRVP及RVI均显著降低（P<0.05），管壁增厚、管腔狭窄的程度明显改善，肺动脉对胰岛素诱导的舒张功能显著提高（P<0.05）；而HPH 3周+PIO组上述指标及特征均无显著性差异。结论: HPH早期即伴有肺动脉胰岛素敏感性减弱，如早期给予PIO治疗，可有效地改善肺血管的舒张功能和肺血管重建、显著降低肺动脉压力，而后期治疗则对肺血管功能及肺动脉压无影响，提示肺动脉胰岛素抵抗在HPH发生中的重要作用及早期干预的必要性。
Abstract:
AIM:To investigate the changes of insulin sensitivity of pulmonary artery in hypoxic pulmonary Hypoxic pulmonary hypertension (HPH) rats and the influence of pioglitazone (PIO) treatment at different stages of the disease process and to analyze the role of insulin resistance in the development of hypoxic pulmonary hypertension. METHODS: Twentyeight male SD rats were randomly divided into 4 equal groups: normal group, HPH group, HPH 2nd week PIO group and HPH 4th week PIO group. Rats in HPH group, HPH 2nd week PIO group and HPH 4th week PIO group were exposed to lowpressure and lowoxygen condition in an automodulating hypobaric and hypoxic cabin (air pressure 50 kPa, 8 hours every day for 4 weeks) to establish HPH the animal model. HPH 2nd week PIO group and HPH 4th week PIO group were treated with PIO ［10 mg/(kg·d)］ in the second week and fourth week respectively. After 4week lowpressure and lowoxygen exposure, glucometer and ELISA method were used respectively to determinate the level of fasting blood glucose (FBG) and fasting serum insulin (FSI),then the insulin resistance index (IRI) was calculated. A microcatheter was inserted into right ventricle and pulmonary artery through right external jugular vein, and the mean pulmonary arterial pressure (mPAP) and mean right ventricular pressure (mRVP) were measured, then right ventricle index (RVI) was calculated. The changes of pulmonary vascular microstructure were observed through HE staining. The main pulmonary artery was isolated from rat. Vasodilation effect of insulin on pulmonary artery rings pretreated with phenephrine (PE) was investigated by perfusion technique in vitro. RESULTS: Compared with those in control group, fasting bloodglucose (FBG), fasting serum insulin (FSI), insulin resistance index (IRI), mean pulmonary arterial pressure (mPAP), right ventricular pressure (RVP) and right ventricle index (RVI) were significantly enhanced in HPH group (P<005). HE staining showed hyperplasia in pulmonary artery smooth muscle and elastic fiber layer, wall thickening and vessel stenosis. Insulin induced vasorelaxation reaction was significantly attenuated (P<005). Compared with those in HPH group, FPG, FIN, IRI, mPAP, mRVP and RVI decreased in HPH 2nd week PIO group (P<005). Wall thickening and vessel stenosis were significantly reduced and insulin induced vasorelaxation reaction was also significantly improved (P<005). However, compared with these changes, no significant difference was observed in HPH 4th week PIO group. CONCLUSION: Insulin resistance of pulmonary artery plays an important role in the development of hypoxiainduced pulmonary hypertension and early treatment is very necessary.

参考文献/References

[1]Rubin LJ.Primary pulmonary hypertension[J].N Engl J Med,1997,336(2):111-117.
[2]Humbert M,Khaltaev N,Bousquet J,et al.Pulmonary hypertension:from an orphan disease to a public health problem[J].Chest,2007,132(2):365-367.
[3]Zamanian RT,Hansmann G,Snook S,et al.Insulin resistance in pulmonary arterial hypertension[J].Eur Respir J,2009,33(2):318-324.
[4]Hansmann G, Wagner RA, Schellong S, et al. Pulmonary arteria1 hypertension is linked to insulin resistance And reversed by peroxisome proliferato activated receptor gamma activation[J]. Circulation, 2007, 115(10):1275-1284.
[5]Li R, Zhang HF, Wang WQ, et al. Vascular insulin resistance in prehypertensive rats: Role of PI3 kinase/Akt/eNOS signaling[J].Eur J Pharmacol,2010,628(1-3):140-147.
[6]李光伟，潘孝仁，Liuioja S,等.检测人群胰岛素敏感性一项新指数[J].中华内科杂志,1993,32(8):656-660.
[7]孙 波,刘文利.右心导管法测定大鼠肺动脉高压的实验方法[J].中国医学科学院学报,1984,6(6):465-467.
[8]Sun X,Ma S,Zang YM,et al.Vasorelaxing effect of U50,488H in pulmonary artery and underlying mechanism in rats[J].Life Sci,2006,78(21):2516-2522.
[9]Cusi K,Maezono K,Oaman A,et al.Insulin resistance differentially affects the PI3Kinase and MAP Kinase mediated signaling in human muscle[J].J Clin Invest,2000,105(3):311-320.
[10]Kubok I K,Jiang ZY,Takahara N,et al.Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo:a specific vascular action of insulin[J]. Circulation,2000,101(6):676-681.
[11]Demareo VG,Whaley Connell AT,Sowers JR,et al. Contribution of oxidative stress to pulmonary arterial hypertension[J].World J Cardiol,2010,2(10):316-324.
[12]Ozaki M,Kawashima S,Yamashita T,et al.Reduced hypoxic pulmonary vascular remodeling by nitric oxide from the endothelium[J].Hypertension,2001,37(2):322-327.
[13]Steudel W,Scherrer Crosbie M,Bloch KD,et al.Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital defitciency of nitric oxide synthase 3[J].J Clin Invest,1998,101(11):2468-2477.
[14]BirreU MA,Patel HJ,McCluskie K,et al.PPAR gamma agonists as therapy for diseases involving airway neutrophilia[J].Eur Respir J,2004,24(1):18-23.
[15]Matsuda Y,Hoshikawa Y,Ameshima S,et al.Effects of peroxisome pmliferator activated receptor gamma ligands on monocrotaline induced pulmonary hypertension in rats[J].Nihon Kokyuki Gakkai Zasshi,2005,43(5):283-288.
[16]孙红花,安昌善.天甲美对大鼠低氧性肺动脉高压及肺血管重建的影响[J].中国老年病学杂志,2008,28(17):1699-1700.

备注/Memo

备注/Memo:
收稿日期：2013-01-23.
基金项目：国家自然科学基金资助（30700345，81270330）
通讯作者：孙新，副教授，从事肺动脉高压研究Email:sunxin6@fmmu.edu.cn 共同通讯作者：张海锋，讲师，从事心血管胰岛素抵抗研究Email:hfzhang@fmmu.edu.cn 作者介绍：范芳，硕士生Email:fanfang6628@sina.com
更新日期/Last Update: 2013-07-16