通心络对低压低氧性肺动脉高压大鼠HIF-1α及相关因子的作用
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- 英文论文题名：The Effect of Tongxinluo on ⅢF-1α and Related Factors Level in Rats with Ilypobaric and Ilypoxia Pulmonary Ilypertension
- 论文作者：周晓玲 ; 潘磊 ; 马婷婷 ; 郭蕊 ; 江宏 ; 姚小燕 ; 高志敏 ; 王勇
- 英文论文作者：ZHOU Xiao-ling ; PAN Lei ; MA Ting-ting ; GUO Rui ; JIANG Hong ; YAO Xiao-yan ; GAO Zhi-Min ; WANG Yong ; Department of Geratology ; Beijing Shijitan Hospital ; Capital Medical University ; Hypoxia Laboratory ; Beijing Shijitan Hospital ; Capital Medical University ; The Ninth Clinical Hospital of Peking University ; Labor of Animal Experiment ; Beijing Shijitan Hospital ; Capital Medical University
- 年：2016
- 作者机构：首都医科大学附属北京世纪坛医院老年医学科;首都医科大学附属北京世纪坛医院低氧实验室;北京大学第九临床医学院;首都医科大学附属北京世纪坛医院动物实验中心;
- 论文关键词：通心络 ; 低压低氧性肺动脉高压 ; 缺氧诱导因子-1α ; 大鼠
- 英文论文关键词：Tongxinluo ; Hypobaric and hypoxia pulmonary hypertension ; Hypoxia-inducible factor-1α ; Rat
- 会议召开时间：2016-06-25
- 会议录名称：青藏铁路运营十周年学术研讨会卫生系统论文集
- 语种：中文
- 分类号：R285.5
- 学会代码：ZGTD
- 会议名称：青藏铁路运营十周年学术研讨会
- 会议地点：中国西藏拉萨
- 主办单位：中国铁道学会、青海省科学技术协会、西藏自治区科学技术协会
- 学会名称：中国铁道学会
- 页数：4
- 文件大小：350k
- 原文格式：O
- 会议级别：全国
摘要
目的:探讨通心络对低压低氧性肺动脉高压大鼠缺氧诱导因子-1α(HIF-1α)及相关因子的影响。方法:30只体重200-250g的SD雄性大鼠,随机分为常压常氧对照组(对照组)、低压低氧模型组(模型组)、低压低氧十通心络干预组(通心络干预组),每组10只。采用低压低氧舱模拟海拔5000m的高原环境(大气压50kp,氧浓度10%)。模型组和通心络干预组大鼠每日入舱8h,其余时间为常压常氧环境。通心络干预组每天入舱前给予通心络1.2g生药/kg灌胃1次,对照组于同-实验室的常压常氧环境中饲养。4周后比较各组大鼠平均肺动脉压(mPAP)、右心室(RV)肥厚指数以及血清HIF-1α、血管内皮生长因子(VEGF)、内皮素-1(ET-1)等因子水平。结果:4周后,与对照组相比,模型组大鼠mPAP、RV肥厚指数及HIF-1α、VEGF、ET-1等因子水平显著升高(P<0.05)。与模型组相比,通心络干预组大鼠mPAP、RV肥厚指数及血清HIF-1α、VEGF、ET-1等因子水平均显著降低(P<0.05),且RV肥厚指数及血清HIF-1α、ET-1水平与对照组水平差异无统计学意义(P>0.05)。结论:通心络可能通过降低HIF-1α水平等干预低压低氧性肺动脉高压的发生发展。
Objective:To study the eflect of Tongxinluo on HIF-1α in rats with hypobaric and hypoxia pulmonary hypertension.Method:30 male SD rats weighing 200-250 g were randomly divided into three groups-,control group with normal pressure and normal oxygen(control group),pulmonary hypertension group with low-pressure and low-oxygen(model group),and the group treated by Tongxinluo in low-pressure and low-oxygen condition(Tongxinluo intervention group).Each group included 10 rats.Auto-modulating hypobaric and hypoxic cabin was used to simulate 5000 m high altitude environment(air pressure 50 kpa,oxygen concentration 10%).Tongxinluo(1.2g/kg crude drug) was given by gastrogavage to rats in Tongxinluo intervention group once daily.Control group were exposed to normal-pressure and normahoxygen in the same laboratory environment.4 weeks later,the mean pulmonary arterial pressure(mPAP) and right ventricular(RV) mass index were measured.Concentrations of HIF-1α,VEGF and ET-1 in blood were detected.Results:Compared with control group,TnPAP,RV mass index and the levels of HIF-1α,VEGF,ET-1 in model group were significantly increased(P<0.05).Compared with model group,rats of Tongxinluo intervention group showed lower mPAP and RV mass index,and the levels of HIF-1α,VEGF and ET-1 decreased remarkably(P<0.05).There was no significant difference between control group and Tongxinluo intervention group in right ventricular hypertrophy index and the levels of serum HIF-1α and ET-1(P>0.OS).Conclusion:Tongxinluo may influence the occurrence and development of hypobaric and hypoxia pulmonary hypertension by downregulated the level of HIF-1α.
Objective:To study the eflect of Tongxinluo on HIF-1α in rats with hypobaric and hypoxia pulmonary hypertension.Method:30 male SD rats weighing 200-250 g were randomly divided into three groups-,control group with normal pressure and normal oxygen(control group),pulmonary hypertension group with low-pressure and low-oxygen(model group),and the group treated by Tongxinluo in low-pressure and low-oxygen condition(Tongxinluo intervention group).Each group included 10 rats.Auto-modulating hypobaric and hypoxic cabin was used to simulate 5000 m high altitude environment(air pressure 50 kpa,oxygen concentration 10%).Tongxinluo(1.2g/kg crude drug) was given by gastrogavage to rats in Tongxinluo intervention group once daily.Control group were exposed to normal-pressure and normahoxygen in the same laboratory environment.4 weeks later,the mean pulmonary arterial pressure(mPAP) and right ventricular(RV) mass index were measured.Concentrations of HIF-1α,VEGF and ET-1 in blood were detected.Results:Compared with control group,TnPAP,RV mass index and the levels of HIF-1α,VEGF,ET-1 in model group were significantly increased(P<0.05).Compared with model group,rats of Tongxinluo intervention group showed lower mPAP and RV mass index,and the levels of HIF-1α,VEGF and ET-1 decreased remarkably(P<0.05).There was no significant difference between control group and Tongxinluo intervention group in right ventricular hypertrophy index and the levels of serum HIF-1α and ET-1(P>0.OS).Conclusion:Tongxinluo may influence the occurrence and development of hypobaric and hypoxia pulmonary hypertension by downregulated the level of HIF-1α.
引文
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2 Xu XQ,Jing ZC.High-altitude pulmonary hypertension[J].Eur Respir Rev,2009,18(111):13-17.
3 Xu Y,Liu Y,Liu J,et al.Meta-analysis of clinical ellicacy ol sildenafil,a phosphodiesterase type-5 inhibitor on high altitude hypoxia and its complications[J].High All Med Biol,2014,15(1):46-51.
4 Bates MG,Thompson AA,Baillie JK,et al.Sildenafil citrate for the prevention ol high altitude hypoxic pulmonary hypertension,double blind,randomized,placebo-controlled trial[J].High Alt Med Biol,2011,12(3):207-214.
5 Cheng YT,Yang YJ,Zhang HT,et al.Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through anitricoxide related mechanism[J].Chin Med J(Engl),2009,122(13):1 529-1 538.
6 Yao EH,Wang HJ,Xu CS.Effects of tongxinluo on the neointrma formation and expression of inflammatory cytokines in rats after carotid artery balloon injury[J].Indian J Pharmacol,2014,46(5).510-514.
7徐贵成,高荣林,吴以岭,等.通心络胶囊治疗冠心病心绞痛的临床研究[J].中国中西医结舍杂志,1997,17(7):414-416.
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9吴士珍,吴相锋,袁国强,等.缺氧大鼠血管内皮功能的变化及通心络超微粉的干预作用[J].疑难病杂志,2009,8(3):131-134.
10李娟,孙新,毕辉,等.低压低氧性大鼠肺动脉高压模型的建立[J].临床心血管杂志,2008,4(4);297-301.
11 Ryan J,Bloch K,Archer SL.Rodent models of pulmonary hypertension:harmonisalion with the world health organisation's categorisation of buman PH[J].Int J Clin Pract,2011,65(172Suppl):15-34.
12 Humbert M,Morrell NW,Archer SL,et al.Cellular and molecular pathobiology of pulmonary arterial hypertension[J].J Am Coil Cardiol,2004,43(12 Suppl S):13S-24S.
13 Wang Z,Chesler NC.Pulmonary vascular mechanics:important contributors to the increased right ventricular afterload of pulmonary hypertension[J].Exp Physiol,2013,98(8):1 267-1 273.
14 Ortmann B,Druker J,Rocha S.Cell cycle progression in respose to oxygen levels[J].Cell Mol Life Sci,2014,71(18):3 569-3 582.
15 Niu G,Briggs J,Deng J,et al.Signal transducer and activator of transcription is required for hypoxia-inducible factor-1 alpha RNA expression in both tumor cells and tumor associated myeloid cells[J].Mol Cancer Res,2008.6(7):1 099-1 105.
16吴相春,吴相峰,贾振华,等,通心络对小鼠反复缺氧耐受性的影响[J].中华医学杂志,2010,90(22):1 571-1573.
2 Xu XQ,Jing ZC.High-altitude pulmonary hypertension[J].Eur Respir Rev,2009,18(111):13-17.
3 Xu Y,Liu Y,Liu J,et al.Meta-analysis of clinical ellicacy ol sildenafil,a phosphodiesterase type-5 inhibitor on high altitude hypoxia and its complications[J].High All Med Biol,2014,15(1):46-51.
4 Bates MG,Thompson AA,Baillie JK,et al.Sildenafil citrate for the prevention ol high altitude hypoxic pulmonary hypertension,double blind,randomized,placebo-controlled trial[J].High Alt Med Biol,2011,12(3):207-214.
5 Cheng YT,Yang YJ,Zhang HT,et al.Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through anitricoxide related mechanism[J].Chin Med J(Engl),2009,122(13):1 529-1 538.
6 Yao EH,Wang HJ,Xu CS.Effects of tongxinluo on the neointrma formation and expression of inflammatory cytokines in rats after carotid artery balloon injury[J].Indian J Pharmacol,2014,46(5).510-514.
7徐贵成,高荣林,吴以岭,等.通心络胶囊治疗冠心病心绞痛的临床研究[J].中国中西医结舍杂志,1997,17(7):414-416.
8尤士杰,陈可冀,杨跃进,等.通心络胶囊干预急性心肌梗死早期血运重建后自发性改善的临床研究[J].中国中西医结合中2005,25(7):604-607.
9吴士珍,吴相锋,袁国强,等.缺氧大鼠血管内皮功能的变化及通心络超微粉的干预作用[J].疑难病杂志,2009,8(3):131-134.
10李娟,孙新,毕辉,等.低压低氧性大鼠肺动脉高压模型的建立[J].临床心血管杂志,2008,4(4);297-301.
11 Ryan J,Bloch K,Archer SL.Rodent models of pulmonary hypertension:harmonisalion with the world health organisation's categorisation of buman PH[J].Int J Clin Pract,2011,65(172Suppl):15-34.
12 Humbert M,Morrell NW,Archer SL,et al.Cellular and molecular pathobiology of pulmonary arterial hypertension[J].J Am Coil Cardiol,2004,43(12 Suppl S):13S-24S.
13 Wang Z,Chesler NC.Pulmonary vascular mechanics:important contributors to the increased right ventricular afterload of pulmonary hypertension[J].Exp Physiol,2013,98(8):1 267-1 273.
14 Ortmann B,Druker J,Rocha S.Cell cycle progression in respose to oxygen levels[J].Cell Mol Life Sci,2014,71(18):3 569-3 582.
15 Niu G,Briggs J,Deng J,et al.Signal transducer and activator of transcription is required for hypoxia-inducible factor-1 alpha RNA expression in both tumor cells and tumor associated myeloid cells[J].Mol Cancer Res,2008.6(7):1 099-1 105.
16吴相春,吴相峰,贾振华,等,通心络对小鼠反复缺氧耐受性的影响[J].中华医学杂志,2010,90(22):1 571-1573.