血管生成性T淋巴细胞对间歇性缺氧大鼠早期动脉粥样硬化的影响
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南京医科大学附属无锡人民医院

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国家自然科学基金项目(面上项目,重点项目,重大项目)


Effect of angiogenic T lymphocytes on early atherosclerosis in intermittent hypoxic rats
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    摘要:

    目的:探讨慢性间歇性缺氧(chronic intermittent hypoxia;CIH)暴露下,大鼠外周血中血管生成性T淋巴细胞(angiogenic T-cells,Tang)水平变化对早期动脉粥样硬化的影响。方法:将健康成年Sprague Dawley(S-D)大鼠随机分为2组:正常饲养组(RA组)和慢性间歇性缺氧组(IH组),其中IH组接受间歇性缺氧暴露,每天8小时,共6周。间歇性缺氧模式设定为:每2min一个循环,40s内向仓内充入氮气使氧气浓度从21%降到8%并稳定20s,然后充入正常空气使氧气浓度在40s内恢复到21%并维持20s。造模完成后,使用流式细胞法检测Tang及内皮祖细胞(endothelial progenitor cells,EPCs)水平,ELISA法检测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)及同型半胱氨酸(homocysteine,Hcy),制备胸主动脉H&E染色病理切片观察病理改变及测量动脉内中膜厚度。结果:经过6周的慢性间歇性缺氧暴露,Tang水平:IH组(22.975%±1.866%)比RA组(15.713%±1.746%)水平显著升高(P <0.001);EPC水平:IH组(0.04%±0.028%)和RA组(0.028%±0.012%)对比没有统计学差异(P>0.05);动脉内中膜厚度(intima-media thickness,IMT):IH组(121.275μm ± 30.896μm)对比RA组(84.075μm ± 7.452μm)显著增厚(P <0.05);Hcy水平:IH组(6.2μmol/L±0.6μmol/L)比RA组(5.5μmol/L±0.6μmol/L)显著升高(P <0.05);HDL-C、LDL-C、TC、TG水平无统计学差异(P>0.05);结论:在慢性间歇性缺氧导致的动脉粥样硬化早期阶段,血管生成性T淋巴细胞水平升高,能够延缓动脉粥样硬化的发生发展。

    Abstract:

    Objective: To explore the changes in levels of angiogenic T lymphocytes (Tang) in the peripheral blood of rats exposed to chronic intermittent hypoxia (CIH) and their impact on early atherosclerosis. Methods: Healthy adult Sprague Dawley (SD) rats were randomly divided into two groups: the normal feeding group (RA group) and the chronic intermittent hypoxia group (IH group), with the IH exposed to intermittent hypoxia for 8 h per day for a total of 6 weeks. The intermittent hypoxia pattern was set to repeat every 2 min, with 40 s of nitrogen gas to reduce the oxygen concentration from 21% to 8% and stabilize for 20 s, followed by normal air to restore the oxygen concentration to 21% for 40 s and maintain for 20 s. After modeling, levels of Tang and endothelial progenitor cells(EPC)were measured by Flow Cytometry. Levels of high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), total cholesterol(TC) and homocysteine(Hcy)were measured by ELISA. pathological changes were observed in H & E stained pathological sections of the thoracic aorta. Results: Flow cytometry results showed that compared to the RA group, the levels of Tang in rats of the IH group were significantly elevated [(22.975±1.866)% vs. (15.713±1.746)%, P <0.001], and there was no statistical difference in EPC levels [(0.04±0.028)% vs. (0.028±0.012)%, P>0.05]; H&E staining results showed that the IMT of rats thoracic aorta in the IH group was significantly increased compared to the RA group [(121.275±30.896)μm vs. (84.075±7.452)μm, P<0.05]; ELISA experiments indicated that the Hcy level in the IH group was significantly higher compared to the RA group [(6.2±0.6)μmol/L vs.(5.5±0.6)μmol/L, P<0.05], but there were no statistical differences in HDL-C, LDL-C, TC, and TG levels (P>0.05). Conclusion: In the early stage of atherosclerosis induced by CIH, the levels of Tang are elevated and can delay the occurrence and development of atherosclerosis.

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  • 收稿日期:2023-06-26
  • 最后修改日期:2023-11-27
  • 录用日期:2023-12-22
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