摘要
目的观察红景天对间歇低氧(IH)大鼠血管内皮的保护作用并探讨其可能机制.方法将45只雄性成年SD大鼠按随机数字表法分为正常对照组、IH组和红景天低、中、高剂量组,每组9只.将大鼠放入IH模型仓内,向舱内循环冲入氮气、氧气及压缩空气条件下饲养45 d复制IH模型;正常对照组大鼠的饲养仓及饲养时间与其他各组一致,舱内氧浓度持续为20%~21%.红景天高、中、低剂量组于IH 15 d开始腹腔注射红景天0.2、0.1、0.05 mL/100 g,连用30 d.采用全自动生化仪检测大鼠冠状动脉(冠脉)血管中丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)水平;采用酶联免疫吸附试验(ELISA)检测大鼠冠脉组织缺氧诱导因子-1α(HIF-1α)、肿瘤坏死因子-α(TNF-α)含量;采用反转录-聚合酶链反应(RT-PCR)检测冠脉组织内皮素-1(ET-1)及血管内皮生长因子(VEGF)的mRNA表达水平;光镜下观察冠脉组织病理学改变.结果与正常对照组比较,IH组SOD、NO均降低〔SOD(U/mg):4.43±0.22比8.60±0.34,NO(μmol/g):3.09±0.07比4.81±0.41,均P<0.01〕,MDA、TNF-α、HIF-1α及ET-1和VEGF的mRNA表达水平均升高〔MDA(nmol/mg):0.78±0.03比0.50±0.03,TNF-α(pg/mg):6.35±0.29比3.27±0.14,HIF-1α(ng/mg):14.55±0.70比7.16±0.17,ET-1 mRNA(2-ΔΔCt):1.75±0.03比1.10±0.07,VEGF mRNA(2-ΔΔCt):4.38±0.10比1.20±0.07,均P<0.01〕.与IH组比较,红景天各剂量组SOD、NO均升高,MDA、TNF-α、HIF-1α和ET-1、VEGF的mRNA表达水平均降低,以红景天高剂量组的变化较红景天低、中剂量组更显著〔SOD(U/mg):7.47±0.19比5.41±0.37、6.71±0.28,MDA(nmol/mg):0.57±0.20比0.74±0.04、0.70±0.03,NO(μmol/g):4.00±0.28比3.27±0.18、3.47±0.28,TNF-α(pg/mg):3.90±0.17比5.08±0.27、4.39±0.26,HIF-1α(ng/mg):8.40±0.23比11.07±0.41、9.81±0.44,ET-1 mRNA(2-ΔΔCt):1.12±0.04比1.71±0.03、1.63±0.07,VEGF mRNA(2-ΔΔCt):2.45±0.09比3.99±0.12、3.27±0.08,均P<0.05〕.光镜下可见正常对照组内膜完整,内皮细胞疏松、淡染突起于内膜表面;IH组动脉部分区内膜水肿甚至脱落,血管壁间质水肿;红景天各剂量组病理改变均较IH组减轻,以红景天高剂量组的改变更为显著.结论红景天可通过提升组织抗缺氧水平、抑制氧化应激和炎症反应,对IH暴露所致血管内皮有保护作用.
Objective To observe the protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia(IH)and to explore its possible mechanism.Methods According to random number table method,45 male Sprague-Dawley(SD)rats were divided into normal control group,IH group and Rhodiola rosea low,medium and high dose groups,with 9 rats in each group.The IH model was reproduced by putting the rats into IH model chamber,and then feeding them with nitrogen,oxygen and compressed air for 45 days.The feeding bin and feeding time of rats in the normal control group were consistent with those in other groups,and the oxygen concentration in the tank was maintained at 20%-21%.The rats in Rhodiola rosea high,medium and low dose groups were intraperitoneally injected with Rhodiola rosea(0.2,0.1 and 0.05 mL/100 g),starting from the 15 th day in IH chamber,and the injection continued for 30 days.The levels of malondialdehyde(MDA),superoxide dismutase(SOD)and nitric oxide(NO)in the coronary arteries of rats in each group were detected by automatic biochemical analyzer.The contents of coronary hypoxia-inducible factor-1α(HIF-1α)and tumor necrosis factor-α(TNF-α)in rats were determined by enzyme linked immunosorbent assay(ELISA).The mRNA expression levels of endothelin-1(ET-1)and vascular endothelial growth factor(VEGF)in coronary artery tissues of rats in each group were measured by reverse transcription-polymerase chain reaction(RT-PCR).The pathological changes of aorta in each group were observed under light microscope.Results Compared with the normal control group,SOD and NO in the IH group decreased[SOD(U/mg):4.43±0.22 vs.8.60±0.34,NO(μmol/g):3.09±0.07 vs.4.81±0.41,both P<0.01],MDA,TNF-α,HIF-1αand mRNA expression of ET-1 and VEGF increased[MDA(nmol/mg):0.78±0.03 vs.0.50±0.03,TNF-α(pg/mg):6.35±0.29 vs.3.27±0.14,HIF-1α(ng/mg):14.55±0.70 vs.7.16±0.17,ET-1 mRNA(2-ΔΔCt):1.75±0.03 vs.1.10±0.07,VEGF mRNA(2-ΔΔCt):4.38±0.10 vs.1.20±0.07,all P<0.01].Compared with the IH group,SOD and NO were increased in three Rhodiola rosea groups,MDA,TNF-α,HIF-1αand mRNA expression of ET-1 and VEGF were decreased in three Rhodiola rosea groups,and the changes in the Rhodiola rosea high dose group were more significant than those in the low and medium dose Rhodiola rosea groups[SOD(U/mg):7.47±0.19 vs.5.41±0.37,6.71±0.28,MDA(nmol/mg):0.57±0.20 vs.0.74±0.04,0.70±0.03,NO(μmol/g):4.00±0.28 vs.3.27±0.18,3.47±0.28,TNF-α(pg/mg):3.90±0.17 vs.5.08±0.27,4.39±0.26,HIF-1α(ng/mg):8.40±0.23 vs.11.07±0.41,9.81±0.44,ET-1 mRNA(2-ΔΔCt):1.12±0.04 vs.1.71±0.03,1.63±0.07,VEGF mRNA(2-ΔΔCt):2.45±0.09 vs.3.99±0.12,3.27±0.08,all P<0.05].Under light microscope,the inner membrane of the normal control group was intact,and the endothelial cells were loose and slightly stained on the surface of the inner membrane;in the IH group,part of the arterial areas showed endointima edema or even abscission,and interstitial edema in the vascular wall.The pathological changes in three Rhodiola rosea groups were less than that in the IH group,and the changes of Rhodiola rosea high dose group were more significant.Conclusion Rhodiola rosea can protect the vascular endothelium caused by IH exposure through improving the level of anti-hypoxia in tissues and inhibiting oxidative stress and inflammatory response.
作者
曹慧
焦婷
吴茂兰
刘维英
Cao Hui;Jiao Ting;Wu Maolan;Liu Weiying(First Clinical Medical College of Lanzhou University,Lanzhou 730000,Gansu,China;Department of Respiratory Medicine,th e First Hospital of Lanzhou University,Lanzhou 730000,Gansu,China)
出处
《中国中西医结合急救杂志》
CAS
CSCD
北大核心
2019年第5期577-580,共4页
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
基金
甘肃省科技计划项目(1506RJZA253)
甘肃省中医药科技研究课题(GZK-2012-39)。
关键词
红景天
间歇低氧
氧化应激
炎症因子
血管内皮
Rhodiola rosea L
Intermittent hypoxia
Oxidative stress
Inflammatory factor
Vascular endothelium
