海南省气候对“候鸟”高血压患者炎性因子和miR-146a的短期影响
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摘要
目的:调查海南省外地(候鸟)高血压人群的血压水平、血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)以及外周血单核细胞(PBMC)内微小RNA (miR)-146a基因表达的3个月内的变化。方法:共纳入90例研究对象,其中高血压组60例和正常对照组30例。测量并记录两组人群初到海南1周内、1个月和3个月后的血压情况,比较两组人群的血清中TNF-α、IL-6和IL-1β以及PBMC内miR-146a基因的表达情况。结果:与1周内相比,高血压患者1个月和3个月收缩压和舒张压明显降低(P均<0.05),TNF-α、IL-1β和IL-6水平以及miR-146a基因表达也明显下调(P<0.05)。miR-146a基因与TNF-α、IL-1β呈显著正相关(P<0.05),而与IL-6无显著相关性(P>0.05)。正常对照组的血压水平、血清炎性因子浓度和miR-146a基因表达在三个时间段无明显差异。结论:高血压患者在海南居住1个月后血压改善,可能与TNF-α、IL-1β和IL-6水平以及miR-146a基因表达降低有关。
Objectives: To investigate the impact of short-term residence in Hainan province on blood pressure,serum levels of TNF-α, IL-1βand IL-6 as well asmicro RNA(miR)-146 a gene expression in peripheral blood mononuclear cells(PBMC) of patients with hypertension. Methods:A total of 60 hypertensive patients and 30 healthy controls, who were not permanent residents of Hainanprovince, arrived Hainan province within 1 week and planned to stay for ≥6 monthswere included.The blood pressure of the two groups was measured and recorded within 1 week(1 st period), 1 month(2~(nd) period) and 3 months(3~(rd) period).The serum levels of TNF-α, IL-1β and IL-6 were detected by ELISA kit. The PBMC were isolated and cultured by Ficoll-Hypaque density gradient centrifugation.The gene expression of miR-146 a in PBMC was detected by Real-time PCR. Results: 1.The systolic and diastolic blood pressure of hypertensive patients was significantly lower in the 2~(nd) and 3~(rd) period than in the 1 st period(P<0.05).There was no significant difference between the 2~(nd) period and 3~(rd) periodof hypertensive patients(P >0.05). 2.The serum concentrations of TNF-α, IL-1βand IL-6 were significantly high in hypertensive patients than in control subjects at all 3 periods, which were significantly lower at 2~(nd) and 3~(rd) period than in 1 st period of hypertensive patients(all P<0.05). 3.The expression of miR-146 a gene in PBMC of hypertensive patients was down-regulated with time, and the expression of miR-146 a gene in the 2~(nd) period and 3~(rd) period was significantly lower than that in the 1 st period(P<0.05) and lower in the 3~(rd) periodthan in the 2~(nd) period(P<0.05). There was a significant positive correlation between miR-146 a with TNF-α and IL-1β(P<0.05), but not with IL-6(P>0.05).The blood pressure level, serum inflammatory cytokineconcentrations and miR-146 a gene expression in the healthy control group were similar throughout the 3 periods(P>0.05).Conclusion:Blood pressure is reduced after 1-month residencefor non-Hainan residents with hypertension, this beneficial effect is possibly mediated through downregulated inflammatory cytokines and miR-146 a gene expression in PBMC.
Objectives: To investigate the impact of short-term residence in Hainan province on blood pressure,serum levels of TNF-α, IL-1βand IL-6 as well asmicro RNA(miR)-146 a gene expression in peripheral blood mononuclear cells(PBMC) of patients with hypertension. Methods:A total of 60 hypertensive patients and 30 healthy controls, who were not permanent residents of Hainanprovince, arrived Hainan province within 1 week and planned to stay for ≥6 monthswere included.The blood pressure of the two groups was measured and recorded within 1 week(1 st period), 1 month(2~(nd) period) and 3 months(3~(rd) period).The serum levels of TNF-α, IL-1β and IL-6 were detected by ELISA kit. The PBMC were isolated and cultured by Ficoll-Hypaque density gradient centrifugation.The gene expression of miR-146 a in PBMC was detected by Real-time PCR. Results: 1.The systolic and diastolic blood pressure of hypertensive patients was significantly lower in the 2~(nd) and 3~(rd) period than in the 1 st period(P<0.05).There was no significant difference between the 2~(nd) period and 3~(rd) periodof hypertensive patients(P >0.05). 2.The serum concentrations of TNF-α, IL-1βand IL-6 were significantly high in hypertensive patients than in control subjects at all 3 periods, which were significantly lower at 2~(nd) and 3~(rd) period than in 1 st period of hypertensive patients(all P<0.05). 3.The expression of miR-146 a gene in PBMC of hypertensive patients was down-regulated with time, and the expression of miR-146 a gene in the 2~(nd) period and 3~(rd) period was significantly lower than that in the 1 st period(P<0.05) and lower in the 3~(rd) periodthan in the 2~(nd) period(P<0.05). There was a significant positive correlation between miR-146 a with TNF-α and IL-1β(P<0.05), but not with IL-6(P>0.05).The blood pressure level, serum inflammatory cytokineconcentrations and miR-146 a gene expression in the healthy control group were similar throughout the 3 periods(P>0.05).Conclusion:Blood pressure is reduced after 1-month residencefor non-Hainan residents with hypertension, this beneficial effect is possibly mediated through downregulated inflammatory cytokines and miR-146 a gene expression in PBMC.
引文
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[21]Wang Q,Yang Z.Does chronic disease influence susceptibility to the effects of air pollution on depressive symptoms in China?[J].Int J Mental Health Systems,2018,12:33.DOI:10.1186/s13033-018-0212-4.
[22]Herweh C,Nordlohne S,Sykora M,et al.Climatic and seasonal circumstances of hypertensive intracerebral hemorrhage in a worldwide Cohort[J].Stroke,2017,48(12):3384-3386.DOI:10.1161/STROKEAHA.117.018779.
[2]Zarruk JG,Greenhalgh AD,David S.Microglia and macrophages differ in their inflammatory profile after permanent brain ischemia[J].Exp Neurol,2017,301(Pt B):120-132.DOI:10.1016/j.expneurol.2017.08.011.
[3]Chomarat P,Banchereau J,Davoust J,et al.IL-6 switches the differentiation of monocytes from dendritic cells to macrophages[J].Nat immunol,2000,1(6):510-514.DOI:10.1038/82763.
[4]Netea MG,Nold-Petry CA,Nold MF,et al.Differential requirement for the activation of the inflammasome for processing and release of IL-1βin monocytes and macrophages[J].Blood,2009,113(10):2324-2335.DOI:10.1182/blood-2008-03-146720.
[5]Herr N,Bode C,Duerschmied D.The effects of Serotonin in immune Cells[J].Front Cardiovasc Med,2017,4.DOI:10.3389/fcvm.2017.00048.
[6]Dixon KB,Davies SS,Kirabo A.Dendritic cells and isolevuglandins in immunity,inflammation,and hypertension[J].Am J Physiol Heart Circ Physiol,2017,312(3):H368-H374.DOI:10.1152/ajpheart.00603.2016.
[7]Small EM,Olson EN.Pervasive roles of micro RNAs in cardiovascular biology[J].Nature,2011,469(7330):336.DOI:10.1038/nature09783.
[8]刘力生.中国高血压防治指南2010[J].中华高血压杂志,2011,19(8):701-708.DOI:10.16439/j.cnki.1673-7245.2011.08.009.
[9]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2016》概要[J].中国循环杂志,2017,32(6):521-530.DOI:10.3969/j.issn.1000-3614.2017.06.001.
[10]吴莹莹,刘洪臣.TNF-α,IL-1β及IL-6与糖尿病及牙周炎之间的关系[J].中华老年口腔医学杂志,2011,9(2):117-121.DOI:10.3969/j.issn.1672-2973.2011.02.016.
[11]张巧云,李思颉,牛敬忠,等.低氧预适应对急性脑梗死小鼠血清TNF-α,IL-1β和IL-6炎性反应因子的影响[J].首都医科大学学报,2016,37(1):89-92.DOI:10.3969/j.issn.1006-7795.2016.01.017.
[12]Li X,Long Q,Cheng X,et al.Shock wave induces biological renal damage by activating excessive inflammatory responses in rat model[J].Inflammation,2014,37(4):1317-1325.DOI:10.1007/s10753-014-9859-4.
[13]Kim Y,Lim HJ,Jang HJ,et al.Portulaca oleracea extracts and their active compounds ameliorate inflammatory bowel diseases in vitro and in vivo by modulating TNF-α,IL-6 and IL-1βsignalling[J].Food Res Int,2018,4(106):335-343.DOI:10.1016/j.foodres.2017.12.058.
[14]姚焰.我国心原性猝死的防治水平亟待提高[J].中国循环杂志,2018,(2):105-106.DOI:10.3969/J.issn.1000-3614.2018.02.001.
[15]Cheung BMY,Woo YC,Fong CHY,et al.GW27-e0845 blood level of fibroblast growth factor 21 and risk of future hypertension[J].J Am Coll Cardiol,2016,68(16):C141.DOI:10.1016/j.jacc.2016.07.531.
[16]Bunck MC,Diamant M,Cornér A,et al.One-year treatment with exenatide improvesβ-cell function,compared with insulin glargine,in metformin-treated type 2 diabetic patients[J].Diabetes Care,2009,32(5):762-768.DOI:10.2337/dc08-1797.
[17]梁冰,彭志晴,梁晶冰,等.地域变化对“候鸟”老人健康状况的影响[J].中华保健医学杂志,2017,19(3):219-222.DOI:10.3969/.issn.1674-33245.2017.03.010.
[18]Taganov KD,Boldin MP,Chang KJ,et al.NF-κB-dependent induction of micro RNA mi R-146,an inhibitor targeted to signaling proteins of innate immune responses[J].Proc Natl Acad Sci USA,2006,103(33):12481-12486.DOI:10.1073/pnas.0605298103.
[19]宋卫华,惠汝太.高血压分子遗传学研究现状[J].中国循环杂志,2012,27(2):155.DOI:10.3969/J.issn.1000-3614.2012.02.023.
[20]车秀芬,张京红,黄海静,等.海南岛气候区划研究[J].热带农业科学,2014,34(6):60-65.
[21]Wang Q,Yang Z.Does chronic disease influence susceptibility to the effects of air pollution on depressive symptoms in China?[J].Int J Mental Health Systems,2018,12:33.DOI:10.1186/s13033-018-0212-4.
[22]Herweh C,Nordlohne S,Sykora M,et al.Climatic and seasonal circumstances of hypertensive intracerebral hemorrhage in a worldwide Cohort[J].Stroke,2017,48(12):3384-3386.DOI:10.1161/STROKEAHA.117.018779.