模拟月尘对大鼠心率变异性及系统炎症的影响
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摘要
目的探讨模拟月尘(lunar dust simulant,LDS)对大鼠心率变异性(heart rate variability,HRV)及系统炎症损伤的影响。方法24只大鼠随机分为对照组(Con),LDS低(0.35mg/只大鼠)、中(1.05mg/只大鼠)、高(3.15mg/只大鼠)3个剂量组,通过气管滴注染毒法建立模拟月尘损伤模型。记录大鼠心率和心率变异性(heart rate variability,HRV)变化,并观察大鼠心脏结构病理变化和血清中炎症因子变化。利用qPCR和Western blot法检测大鼠心脏组织中内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1)基因和蛋白表达水平。结果与对照组相比,在中、高剂量暴露组中心率明显降低,HRV明显改变(P<0.05,P<0.01)。HE染色显示心脏病理特征随LDS剂量的增加而增强,血清检测结果表明系统炎症因子水平增加(P<0.05,P<0.01)。LDS3个剂量暴露组心脏组织iNOS表达明显上调,中、高剂量组ICAM-1表达明显上调(P<0.05,P<0.01)。结论 LDS暴露导致系统炎性病变,影响自主神经功能。同时,LDS可激活血管内皮细胞,损害内皮功能,具有导致心血管疾病的潜在风险。
Objective To investigate the effects of lunar dust simulant(LDS)on heart rate variability(HRV)and systemic inflammatory lesions.Methods Twenty-four rats were randomly divided into control group,LDS low dose group(0.35 mg per rat),LDS middle dose group(1.05 mg per rat)and LDS high dose group(3.15 mg per rat).LDS damage rat models were established by intratracheal instillation of LDS suspension.Heart rate(HR)and heart rate variability(HRV)changes of rats were recorded and HE staining was used to observe the ultrastructure of rat hearts.The levels of inflammatory factors in serum were detected.qPCR and Western blot were used to detect the expression of endothelial nitric oxide synthase(eNOS),inducible nitric oxide synthase(iNOS)and intercellular cell adhesion molecule-1(ICAM-1)in heart tissues of rats.Results Compared with the control group,the HR was significantly decreased and the HRV was significantly changed in the middle and high dose groups(P<0.05,P<0.01).HE staining showed that the pathological features of the hearts increased with the dose of LDS,the levels of systemic inflammatory factors increased(P<0.05,P<0.01).In the heart tissues,the expression of iNOS was significantly up-regulated in LDS exposed groups,and ICAM-1 was significantly up-regulated in middle and high dose groups(P<0.05,P<0.01).Conclusion LDS leads to systemic inflammatory lesions and affects autonomic function.Furthermore,LDS can activate vascular endothelial cells,impair endothelial function leading to potential risk of cardiovascular disease.
Objective To investigate the effects of lunar dust simulant(LDS)on heart rate variability(HRV)and systemic inflammatory lesions.Methods Twenty-four rats were randomly divided into control group,LDS low dose group(0.35 mg per rat),LDS middle dose group(1.05 mg per rat)and LDS high dose group(3.15 mg per rat).LDS damage rat models were established by intratracheal instillation of LDS suspension.Heart rate(HR)and heart rate variability(HRV)changes of rats were recorded and HE staining was used to observe the ultrastructure of rat hearts.The levels of inflammatory factors in serum were detected.qPCR and Western blot were used to detect the expression of endothelial nitric oxide synthase(eNOS),inducible nitric oxide synthase(iNOS)and intercellular cell adhesion molecule-1(ICAM-1)in heart tissues of rats.Results Compared with the control group,the HR was significantly decreased and the HRV was significantly changed in the middle and high dose groups(P<0.05,P<0.01).HE staining showed that the pathological features of the hearts increased with the dose of LDS,the levels of systemic inflammatory factors increased(P<0.05,P<0.01).In the heart tissues,the expression of iNOS was significantly up-regulated in LDS exposed groups,and ICAM-1 was significantly up-regulated in middle and high dose groups(P<0.05,P<0.01).Conclusion LDS leads to systemic inflammatory lesions and affects autonomic function.Furthermore,LDS can activate vascular endothelial cells,impair endothelial function leading to potential risk of cardiovascular disease.
引文
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[19]张建丽.急性心肌梗死后心率变异性和心源性猝死危险性的关系[J].转化医学电子杂志,2015,2(4):51-52.Zhang JL.The relationship between heart rate variability and the risk of sudden cardiac death after acute myocardial infarction[J].E-J Transl Med,2015,2(4):51-52.
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[23]Wihastuti TA,Sargowo D,Soeharto S,et al.Vasa vasorum angiogenesis through increased levels of H2O2,HIF-1α,NF-κB and iNOS:In vivo study of atherosclerosis[J].Journal of Medical and Bioengineering,2015,4(5):342-349.
[24]Guo C,Xia Y,Niu P,et al.Silica nanoparticles induce oxidative stress,inflammation,and endothelial dysfunction in vitro via activation of the MAPK/Nrf2pathway and nuclear factor-κB signaling[J].Int J Nanomedicine,2015,10:1463-1477.
[25]Davies MJ,Gordon JL,Gearing AJ,et al.The expression of the adhesion molecules ICAM-1,VCAM-1,PECAM,and E-selectin in human atherosclerosis[J].J Pathol,1993,171(3):223-229.
[2]Linnarsson D,Carpenter J,Fubini B,et al.Toxicity of lunar dust[J].Planet Space Sci,2012,74(1):57-71.
[3]Rowe WJ.Moon walkers and urban pollution[J].Am JMed,2013,126(7):e1-e2.
[4]Scully RR,Lam CW,James JT.Estimating safe human exposure levels for lunar dust using benchmark dose modeling of data from inhalation studies in rats[J].Inhal Toxicol,2013,25(14):785-793.
[5]Lam CW,Scully RR,Zhang Y,et al.Toxicity of lunar dust assessed in inhalation-exposed rats[J].Inhal Toxicol,2013,25(12):661-678.
[6]Sun Y,Liu JG,Zheng YC,et al.Research on rat’s pulmonary acute injury induced by lunar soil simulant[J].JChin Med Assoc,2018,81(2):133-140.
[7]孙燕,郑洪楠,张贤瑶,等.模拟月尘致大鼠肺脏急性损伤病理学变化[J].航天医学与医学工程,2017,30(2):149-151.Sun Y,Zheng HN,Zhang XY,et al.Pathological changes of acute pulmonary injury in rats induced by tracheal perfusion of lunar soil simulant[J].Space Medicine&Medical Engineering,2017,30(2):149-151.
[8]James JT,Lam CW,Santana PA,et al.Estimate of safe human exposure levels for lunar dust based on comparative benchmark dose modeling[J].Inhal Toxicol,2013,25(5):243-256.
[9]Linnarsson D,Carpenter J,Fubini B,et al.Toxicity of lunar dust[J].Planet Space Sci,2012,74(1):57-71.
[10]William JR.Possible space flight-induced catecholamine cardiomyopathy:Neil Armstrong’s last 20lunar minutes[J].Research Reports in Clinical Cardiology,2014,5:33-39.
[11]Tang H,Li X,Zhang S,et al.A lunar dust simulant:CLDS-i[J].Adv Space Res,2016,59(4):1156-1160.
[12]Wang G,Zhao J,Jiang R,et al.Rat lung response to ozone and fine particulate matter(PM2.5)exposures[J].Environ Toxicol,2015,30(3):343-356.
[13]Liang C,Silva R,West JJ,et al.Multimodel estimates of premature human mortality due to intercontinental transport of air pollution[J].Atmos Chemphys,2018:1-35.
[14]He M,Ichinose T,Kobayashi M,et al.Differences in allergic inflammatory responses between urban PM2.5and fine particle derived from desert-dust in murine lungs[J].Toxicol Appl Pharm,2016,297:41-55.
[15]Wei T,Tang M.Biological effects of airborne fine particulate matter(PM2.5)exposure on pulmonary immune system[J].Environ Toxicol Phar,2018,60:195-201.
[16]Zhang Y,Ji X,Ku T,et al.Inflammatory response and endothelial dysfunction in the hearts of mice co-exposed to SO2,NO2,and PM2.5[J].Environ Toxicol,2016,31(12):1996-2005.
[17]Lee MS,Eum KD,Fang SC,et al.Oxidative stress and systemic inflammation as modifiers of cardiac autonomic responses to particulate air pollution[J].Int J Cardiol,2014,176(1):166-170.
[18]Shafqat K,Pal SK,Kumari S,et al.Empirical mode decomposition analysis of HRV data from patients undergoing local anaesthesia(brachial plexus block)[J].Physiol Meas,2011,32(4):483-497.
[19]张建丽.急性心肌梗死后心率变异性和心源性猝死危险性的关系[J].转化医学电子杂志,2015,2(4):51-52.Zhang JL.The relationship between heart rate variability and the risk of sudden cardiac death after acute myocardial infarction[J].E-J Transl Med,2015,2(4):51-52.
[20]Endukuru CK,Singh SB.A comprehensive study of autonomic dysfunction in hypertension by assessing autonomic function tests and HRV[J].International Journal of Science and Research,2015,4(5):2851-2856.
[21]Peters A,Schneider A,Greven S,et al.Air pollution and inflammatory response in myocardial infarction survivors:Gene-environment interactions in a high-risk group[J].Inhal Toxicol,2007,19(S1):161-175.
[22]Kingery JR,Hamid T,Lewis RK,et al.Leukocyte iNOSis required for inflammation and pathological remodeling in ischemic heart failure[J].Basic Res Cardiol,2017,112(2):19.
[23]Wihastuti TA,Sargowo D,Soeharto S,et al.Vasa vasorum angiogenesis through increased levels of H2O2,HIF-1α,NF-κB and iNOS:In vivo study of atherosclerosis[J].Journal of Medical and Bioengineering,2015,4(5):342-349.
[24]Guo C,Xia Y,Niu P,et al.Silica nanoparticles induce oxidative stress,inflammation,and endothelial dysfunction in vitro via activation of the MAPK/Nrf2pathway and nuclear factor-κB signaling[J].Int J Nanomedicine,2015,10:1463-1477.
[25]Davies MJ,Gordon JL,Gearing AJ,et al.The expression of the adhesion molecules ICAM-1,VCAM-1,PECAM,and E-selectin in human atherosclerosis[J].J Pathol,1993,171(3):223-229.