[1]孟刘坤,滕 晓,袁 雯,等.神经母细胞瘤抑瘤蛋白1在肺动脉高压大鼠中的表达变化[J].中国药理学通报,2019,(09):1226-1231.[doi:10.3969/j.issn.1001-1978.2019.09.009]
 MENG Liu-kun,TENG Xiao,YUAN Wen,et al.Expression change of NBL1 in rats with pulmonary arterial hypertension[J].Chinese Pharmacological Bulletin,2019,(09):1226-1231.[doi:10.3969/j.issn.1001-1978.2019.09.009]
点击复制

神经母细胞瘤抑瘤蛋白1在肺动脉高压大鼠中的表达变化()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年09期
页码:
1226-1231
栏目:
论著
出版日期:
2019-09-09

文章信息/Info

Title:
Expression change of NBL1 in rats with pulmonary arterial hypertension
文章编号:
1001-1978(2019)09-1226-06
作者:
孟刘坤1滕 晓1袁 雯2孟 健1李 君1刘晓艳2
1.中国医学科学院 北京协和医学院 国家心血管病中心阜外医院 心血管疾病国家重点实验室,北京 100037; 2.首都医科大学附属北京朝阳医院医学研究中心,北京 100020
Author(s):
MENG Liu-kun1 TENG Xiao1 YUAN Wen2 MENG Jian1 LI Jun1LIU Xiao-yan2
1.State Key Lab of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; 2.Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
关键词:
野百合碱 肺动脉高压 肺血管重构 神经母细胞瘤抑瘤蛋白1 生物标志物 诊断
Keywords:
monocrotaline pulmonary arterial hypertension pulmonary vascular remodeling neuroblastoma suppression of tumorigenicity 1 biomarker diagnosis
分类号:
R-332; R284.1; R322.12; R322.35; R446.11; R544; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.09.009
文献标志码:
A
摘要:
目的 研究神经母细胞瘤抑瘤蛋白1(neuroblastoma suppression of tumorigenicity 1,NBL1)在野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠中表达的变化。方法 将40只大鼠随机分为对照组(n=10)和MCT组(n=30)。MCT组腹腔注射MCT 60 mg·kg-1,对照组腹腔注射等体积生理盐水; 3周、4周、5周后,检测肺组织和血浆中NBL1的变化。结果 MCT注射后3周、4周、5周,大鼠肺组织NBL1 mRNA水平分别下降了70%、81%和89%,蛋白水平分别下降了36%、78%和99%,而NBL1血浆浓度由对照组的(2.82±0.58)μg·L-1分别下降为(1.90±0.55)μg·L-1、(1.51±0.43)μg·L-1、(0.64±0.34)μg·L-1, 且与肺血流动力学指标及右室肥厚程度均呈明显负相关; 免疫组织化学染色显示,对照组NBL1主要定位于肺小动脉,而MCT组重构肺小动脉鲜有表达; 细胞实验发现,NBL1能明显抑制BMP2/4对肺动脉内皮细胞BMP信号通路的激活。结论 NBL1的表达水平在MCT诱导的PAH中逐渐降低,说明NBL1或在肺血管重构中发挥重要的作用,而其血浆水平可能是PAH潜在的生物标志物。
Abstract:
Aim To study the expression pattern of neuroblastoma, suppression of tumorigenicity 1(NBL1)in pulmonary arterial hypertension(PAH)induced by monocrotaline(MCT).Methods Forty rats were randomly allocated into control group(n=10)and MCT group(n=30).Intraperitoneally injection of 60mg·kg-1 MCT for MCT group or equal volume normal saline for control group was performed.The changes of NBL1 in lungs and plasma of the 3 rd, 4 th and 5 th week after MCT injection were detected respectively.NBL1 levels in rat plasma were detected by enzyme linked immunosorbent assay.Results At the 3 rd, 4 th, and 5 th week after MCT injection, the mRNA level of NBL1 decreased by 70%, 81% and 89%, the protein level decreased by 36%, 78% and 99%, and the plasma concentration of NBL1 decreased from(2.82±0.58)μg·L-1(control rats)to(1.90±0.55)μg·L-1,(1.51±0.43)μg·L-1,(0.64±0.34)μg·L-1 and presented a negative correlation with pulmonary hemodynamic indices and right ventricular hypertrophy.Immunohistochemical staining demonstrated that NBL1 was mainly expressed in small pulmonary arteries in normal lungs from control group but seldom detected in severely remodeled pulmonary arteries from MCT group.Furthermore, NBL1 significantly inhibited the activation of BMP signal in pulmonary artery endothelial cells induced by BMP2/4.Conclusions NBL1 level demonstrates a stepwise decrease in MCT induced PAH, implying its vital roles in the pulmonary vascular remodeling process and the possibility of NBL1 to be a potential biomarker for PAH.

参考文献/References:

[1] Simonneau G, Gatzoulis M A, Adatia I, et al.Updated clinical classification of pulmonary hypertension[J].J Am Coll Cardiol, 2013,62(25 Suppl):D34-41.
[2] Hoeper M M.Definition, classification, and epidemiology of pulmonary arterial hypertension[J].Semin Respir Crit Care Med 2009,30(4):369-75.
[3] Enomoto H, Ozaki T, Takahashi E, et al.Identification of human DAN gene, mapping to the putative neuroblastoma tumor suppressor locus[J].Oncogene, 1994,9(10):2785-91.
[4] Ozaki T, Sakiyama S.Molecular cloning and characterization of a cDNA showing negative regulation in v-src-transformed 3Y1 rat fibroblasts[J].Proc Natl Acad Sci USA 1993,90(7):2593-7.
[5] Stanley E, Biben C, Kotecha S, et al.DAN is a secreted glycoprotein related to Xenopus Cerberus[J].Mech Dev, 1998,77(2):173-84.
[6] Nakamura Y, Ozaki T, Ichimiya S, et al.Ectopic expression of DAN enhances the retinoic acid-induced neuronal differentiation in human neuroblastoma cell lines[J].Biochem Biophys Res Commun, 1998,243(3):722-6.
[7] Hanaoka E, Ozaki T, Nakamura Y, et al.Overexpression of DAN causes a growth suppression in p53-deficient SAOS-2 cells[J].Biochem Biophys Res Commun, 2000,278(1):20-6.
[8] Shinbo J, Ozaki T, Nakagawa T, et al.p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation[J].Biochem Biophys Res Commun, 2002,295(2):501-7.
[9] Ozaki T, Nakamura Y, Enomoto H, et al.Overexpression of DAN gene product in normal rat fibroblasts causes a retardation of the entry into the S phase[J].Cancer Res, 1995,55(4):895-900.
[10] Sun P, Liu W L.Method for measuring pulmonary artery pressure by right cardiac catheter in rats [J].Acta Acad Med Sin, 1984,6(6):465-7.
[11] 刘晓艳,孟刘坤, 李 君, 等.分泌型簇蛋白在肺动脉高压大鼠中的表达变化[J].中国药理学通报, 2014, 30(6):764-8.
[11] Liu X Y, Meng L K, Li J, et al.Expression pattern of secretory clusterin in pulmonary arterial hypertension rats [J].Chin Pharmacol Bull, 2014, 30(6): 764-8..
[12] 陈建新,陈 悦,姚丽华,等.氟西汀抑制慢性应激诱导的小鼠海马胃泌素释放肽受体表达增高[J].中国药理学通报, 2018,38(5):1566-70.
[12] Chen J X,Chen Y,Yao L H, et al.Fluoxetine inhibits the expression of gastrin-releasing peptide receptor in hippocampus of mice induced by chronic stress[J].Chin Pharmacol Bull, 2018, 38(5): 1566-70.
[13] Taisic T, Morrell N W.Smooth muscle cell hypertrophy, proliferation, migration and apoptosis in pulmonary hypertension[J].Compr Physiol, 2011,1(1):295-317.
[14] Strobl M,Schreiber C,Panzenbock A,et al.Exhaled nitric oxide measurement to monitor pulmonary hypertension in a pneumonectomy-monocrotaline rat model[J].Am J Physiol Lung Cell Mol Physiol, 2013,305(7): L485-90.
[15] 吴苏玲,毕立清,孔 辉, 等.鲁斯可皂苷元对野百合碱诱导的肺动脉高压大鼠炎症反应的影响[J].中国药理学通报,2013,29(6):823-7.
[15] Wu S L,Bi L Q,Kong H,et al.Effects of ruscogenin on inflammation of monocrotaline-induced pulmonary artery hypertension in rats[J].Chin Pharmacol Bull, 2013,29(6): 823-7.
[16] Machado R D, Aldred M A, James V, et al.Mutations of the TGF-β typeⅡ receptor BMPR2 in pulmonary arterial hypertension[J].Hum Mutat, 2006,27(2):121-32.

相似文献/References:

[1]杨丹莉,李晓辉,张海港,等.G蛋白抑制肽抑制野百合碱所诱导的右室重构[J].中国药理学通报,2008,(12):0.
 YANG Dan li,LI Xiao hui,ZHANG Hai gang,et al.GCIP27 inhibits the right ventricle remodeling in monocrotalinetreated rats[J].Chinese Pharmacological Bulletin,2008,(09):0.
[2]林全,王良兴,黄晓颖,等.葛根素对缺氧性大鼠肺组织骨桥蛋白及其整合素β3受体基因表达的影响[J].中国药理学通报,2009,(07):0.
 LIN Quan,WANG Liang xing,HUANG Xiao ying,et al.Effects of puerarin on expression of osteopontin and integrin β3 mRNA in lungs of rats induced by hypoxic hypercapnia[J].Chinese Pharmacological Bulletin,2009,(09):0.
[3]林伟,王毅,吴昊.雷公藤甲素对肺动脉高压大鼠肺细小动脉尾加压素Ⅱ表达的影响[J].中国药理学通报,2010,(04):557.
 LIN Wei,WANG Yi,WU Hao.Effect of Triptolide on the protain expression of urotensinⅡ of pulmonary arteries in monocrotaline(MCT)induced SpragueDawley(SD)rats[J].Chinese Pharmacological Bulletin,2010,(09):557.
[4]吴苏玲,毕立清,孔辉,等.鲁斯可皂苷元对野百合碱诱导的肺动脉高压大鼠炎症反应的影响[J].中国药理学通报,2013,(06):823.
 WU Su ling,BI Li qing,KONG Hui,et al.Effects of ruscogenin on inflammation of monocrotalineinduced pulmonary artery hypertension in rats[J].Chinese Pharmacological Bulletin,2013,(09):823.
[5]胡莹,焦海霞,王瑞幸,等.三七皂苷R1对肺高压大鼠模型肺动脉的舒张作用[J].中国药理学通报,2013,(11):1572.
 HU Ying,JIAO Hai xia,WANG Rui xing,et al.Vasodilation of notoginsenoside R1 on pulmonary arteries of pulmonary hypertensive rats[J].Chinese Pharmacological Bulletin,2013,(09):1572.
[6]刘晓艳,孟刘坤,李君,等.分泌型簇蛋白在肺动脉高压大鼠中的表达变化[J].中国药理学通报,2014,(06):764.
 LIU Xiao-yan,MENG Liu-kun,LI Jun,et al.Expression pattern of secretory clusterin in pulmonary arterial hypertension rats[J].Chinese Pharmacological Bulletin,2014,(09):764.
[7]王寒明,王怀良,艾秀丽,等.泛素羧基末端水解酶L1在氟西汀抑制大鼠肺动脉高压中的作用[J].中国药理学通报,2015,(09):1244.[doi:10.3969/j.issn.1001-1978.2015.09.013]
 WANG Han-ming,WANG Huai-liang,AI Xiu-li,et al.Role of UCH-L1 in protection of fluoxetine against pulmonary arterial hypertension in rats[J].Chinese Pharmacological Bulletin,2015,(09):1244.[doi:10.3969/j.issn.1001-1978.2015.09.013]
[8]卢志强,张艳军,庄朋伟,等.肺动脉压的检测方法优化研究[J].中国药理学通报,2015,(07):1028.[doi:10.3969/j.issn.1001-1978.2015.07.028]
 LU Zhi-qiang,ZHANG Yan-jun,ZHUANG Peng-wei,et al.Optimization of detection method of pulmonary arterial pressure[J].Chinese Pharmacological Bulletin,2015,(09):1028.[doi:10.3969/j.issn.1001-1978.2015.07.028]
[9]王瑞幸,戴耄,穆云萍,等.三七皂苷R1对肺高压大鼠肺动脉平滑肌细胞SOCE的抑制作用[J].中国药理学通报,2015,(10):1463.
 WANG Rui xing,DAI Mao,MU Yun ping,et al.Inhibition of notoginsenoside R1 on SOCE in pulmonary arterial smooth muscle cells of pulmonary hypertension rats[J].Chinese Pharmacological Bulletin,2015,(09):1463.
[10]齐元麟,陈富华,任正肖,等.动脉平滑肌细胞的钙池操纵钙通道对细胞自噬的调节[J].中国药理学通报,2016,(10):1416.[doi:10.3969/j.issn.1001-1978.2016.10.017]
 QI Yuan-lin,CHEN Fu-hua,REN Zheng-xiao,et al.Regulation of autophagy by store-operated calcium channel in arterial smooth muscle cells[J].Chinese Pharmacological Bulletin,2016,(09):1416.[doi:10.3969/j.issn.1001-1978.2016.10.017]

备注/Memo

备注/Memo:
收稿日期:2019-05-16,修回日期:2019-06-15
基金项目:国家自然科学基金青年基金(No 81400034,81500038); 北京市自然科学基金面上项目(No 7172182,7172078); 北京朝阳医院1351人才培养计划(No CYXX-2017-36)
作者简介:孟刘坤(1982-),男,博士,主治医师,研究方向:肺动脉高压,E-mail: menglk@126.com;
刘晓艳(1983-),女,博士,助理研究员,研究方向: 肺动脉高压,通讯作者,E-mail:lxy-213@163.com
更新日期/Last Update: 2019-08-14