孤儿肽在肺动脉高压大鼠中的表达
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摘要
目的:探讨孤儿肽(orphanin FQ,OFQ)在肺动脉高压大鼠肺动脉组织及血浆中表达水平变化意义。方法:20只雄性SD大鼠随机分为肺动脉高压诱导组(n=15)和对照组(n=5),肺动脉高压诱导组采用腹腔注射野百合碱(monocrotaline,MCT)60mg/kg体重,对照组腹腔注射等体积的0.9%生理盐水。在注射野百合碱7、14、21、28d后,检测大鼠肺组织中m RNA的表达情况,并应用免疫组织化学技术定位OFQ在肺动脉组织中表达。结果:OFQ在肺动脉高压大鼠肺组织中表达随时间增加呈现正相关,同时在血浆中OFQ表达变化随着肺动脉高压进展而增加,OFQ表达变化与肺动脉血液动力学指标及右心室肥厚指数呈现明显相关性,免疫组化显示OFQ定位于肺小动脉的内皮细胞及平滑肌细胞。结论:OFQ在野百合碱诱导的肺动脉高压大鼠血浆及肺动脉中表达升高,它可以作为判定肺动脉高压严重程度的重要指标,可能参与肺动脉高压发病血管重塑机制。
Objective:To investigate the expression of orphanin FQ in pulmonary artery and serum of rats with pulmonary arterial hypertension( PAH).Methods:Twenty rats were randomly divided into PAH group( n = 15),which were intraperitoneally injected 60 mg/kg MCT; and equal volume of normal saline for control group( n = 5).Reverse transcription-polymerase chain reaction( RT-PCR) was used to investigate the expression level of OFQ mRNA and protein.The immunohisto chemical method was performed to confirm the localization of OFQ in pulmonary artery of PAH.Results:The expression of OFQ mRNA and protein increased significantly in MCT group,and the positive immunohisto reactive OFQ was detected in tissues of PAH,as well as mainly localized in smooth cells and endothelium cells.Conclusion:OFQ was increased significantly in MCT induced by PAH,and it may be as a biomarker to estimate the severity of PAH,and take part in the remodeling process of the pulmonary vascular.
Objective:To investigate the expression of orphanin FQ in pulmonary artery and serum of rats with pulmonary arterial hypertension( PAH).Methods:Twenty rats were randomly divided into PAH group( n = 15),which were intraperitoneally injected 60 mg/kg MCT; and equal volume of normal saline for control group( n = 5).Reverse transcription-polymerase chain reaction( RT-PCR) was used to investigate the expression level of OFQ mRNA and protein.The immunohisto chemical method was performed to confirm the localization of OFQ in pulmonary artery of PAH.Results:The expression of OFQ mRNA and protein increased significantly in MCT group,and the positive immunohisto reactive OFQ was detected in tissues of PAH,as well as mainly localized in smooth cells and endothelium cells.Conclusion:OFQ was increased significantly in MCT induced by PAH,and it may be as a biomarker to estimate the severity of PAH,and take part in the remodeling process of the pulmonary vascular.
引文
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[2]Meunier JC,Mollereau C,Toll L,et al.Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor[J].Nature,1995,377:532-535
[3]Mc Donald J,Leonard AD,Serrano-Gomez A,et al.Assessment of nociceptin/orphanin FQ and micro-opioid receptor m RNA in the human right atrium[J].British journal of anaesthesia,2010,104:698-704
[4]Nothacker HP,Reinscheid RK,Mansour A,et al.Primary structure and tissue distribution of the orphanin FQ precursor[J].Proceedings of the National Academy of Sciences of the United States of America,1996,93:8677-8682
[5]Kapusta DR,Sezen SF,Chang JK,et al.Diuretic and antinatriuretic responses produced by the endogenous opioid-like peptide,nociceptin(orphanin FQ)[J].Life sciences,1997,60:15-21
[6]Okuda-Ashitaka E,Ito S.Nocistatin:a novel neuropeptide encoded by the gene for the nociceptin/orphanin FQ precursor[J].Peptides,2000,21:1101-1109
[7]Mollereau C,Simons MJ,Soularue P,et al.Structure,tissue distribution,and chromosomal localization of the prepronociceptin gene[J].Proceedings of the National Academy of Sciences of the United States of America,1996,93:8666-8670
[8]Stenmark KR,Meyrick B,Galie N,et al.Animal models of pulmonary arterial hypertension:the hope for etiological discovery and pharmacological cure[J].American journal of physiology Lung cellular and molecular physiology,2009,297:1013-1032
[9]Champion HC,Wang R,Hellstrom WJ,et al.Nociceptin,a novel endogenous ligand for the ORL1 receptor,has potent erectile activity in the cat[J].The American journal of physiology,1997,273:214-219