Therapeutic effects of Qishen Yiqi Dropping Pill on myocardial injury induced by chronic hypoxia in rats

The present study was designed to determine the effects of a traditional Chinese medicine, called Qishen Yiqi Dropping Pill on chronic hypoxia-induced myocardial injury. To establish a rat chronic hypoxia model to be used in the evaluation of the therapeutic effects of the Qishen Yiqi Dropping Pill, Sprague-Dawley(SD) rats were randomly divided into three groups: the control, model, and treatment groups(n = 10 per group). The animals were housed in a plexiglass container. The control animals were under normal oxygen concentration and the model and treatment groups were exposed to air and nitrogen for 5 weeks. The rats in the treatment group were orally administered the Qishen Yiqi Dropping pill(35 mg·kg-1·d-1) for 5 weeks. After the treatment, the cardiac function and morphology were analyzed, and the expression levels of hypoxia-inducible factor 1α(HIF-1α) were determined using Western blotting. Our results indicated that the cardiac function was impaired, cell apoptosis was enhanced, and HIF-1α expression was up-regulated in the model group, compared to the control group. These changes were ameliorated by the treatment with the Qishen Yiqi Dropping Pill. In conclusion, Qishen Yiqi Dropping pill can ameliorate myocardial injury induced by chronic hypoxia, improve cardiac function, and decrease myocardial cell apoptosis, which may provide a basis for its clinical use for the treatment of chronic cardiovascular

Establishment and Characterization of Chronic-hypoxia-resistant Gastric Cancer Cell Line MNK45/HYP

The chronic-hypoxia-resistant gastric cancer cell line was established,and its biological characteristics were explored and compared with the parental cell line.Gastric cancer cell lines were cultured under the degressive oxygen concentration.Cell doubling time was calculated by cell counting method.Chemo-resistance ability of cells was tested by MTT assay.Irradiation tolerance of cells was evaluated by colony forming method.Cell cycle distribution was tested with flow cytometry.Invasive ability was tested by Transwell method.The expression levels of GLUT-1 and HIF-1α were detected by using Western blot.MNK45/HYP cells successfully survived under the 1% concentration of oxygen and its cell doubling time was 35.01±1.02 h,while that of MNK45 was 27.35±0.83 h（P〈0.01）.The percentage of MNK45/HYP cells in G0/G1 stage was（58.3±6.1）%,and that of MNK45 cells was（42.2±6.0）%（P〈0.05）.Comparing with the parental cells MNK45,drug resistance indexes of 5-Fu,PTX,OXA,Sn38,GEM and VP16 in MNK45/HYP cells were respectively 5.3,1.3,3.6,2.2,4.8 and 4.4.Colony forming ability of MNK45/HYP cells after irradiation was also significantly higher than MNK45 cells.The invasive number of MNK45/HYP cells was 107.7±17.5,while that of MNK45 cells was 59.0±9.9.The expression levels of GLUT-1 and HIF-1α in MNK45/HYP cells were significantly higher than those in MNK45 cells.MNK45/HYP cells hold biological characteristics of hypoxia tumor with good tolerance to chronic hypoxia,and can be used for the research of solid tumor under chronic hypoxia condition.

Epigenetic modifications of chronic hypoxiamediated neurodegeneration in Alzheimer’s disease

Alzheimer’s disease(AD)is the most common neurodegenerative disorder affecting the elderly people.AD is characterized by progressive and gradual decline in cognitive function and memory loss.While familial early-onset AD is usually associated with gene mutations,the etiology of sporadic late-onset form of AD is largely unknown.It has been reported that environmental factors and epigenetic alterations significantly contribute to the process of AD.Our previous studies have documented that chronic hypoxia is one of the environmental factors that may trigger the AD development and aggravate the disease progression.In this review,we will summarize the pathological effects of chronic hypoxia on the onset and development of AD and put forward the possible molecule mechanisms underlying the chronic hypoxia mediated AD pathogenesis.Finally,we propose that epigenetic regulations may represent new opportunity for the therapeutic intervention of this disease.

The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion

The acute myocardial infarction(AMI)and sudden cardiac death(SCD),both associated with acute cardiac ischemia,are one of the leading causes of adult death in economically developed countries.The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine.A study on the cardiovascular effects of chronic hypoxia(CH)may contribute to the development of these methods.Chronic hypoxia exerts both positive and adverse effects.The positive effects are the infarct-reducing,vasoprotective,and antiarrhythmic effects,which can lead to the improvement of cardiac contractility in reperfusion.The adverse effects are pulmonary hypertension and right ventricular hypertrophy.This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion.It is an in-depth analysis of the published data on the underlying mechanisms,which can lead to future development of the cardioprotective effect of CH.A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.

Phosphorylation of PTEN increase in pathological right ventricular hypertrophy in rats with chronic hypoxia induced pulmonary hypertension

Background Phosphatase and tensin homologue on chromosome ten （PTEN） acts as a convergent nodal signalling point for cardiomyocyte hypertrophy,growth and survival.However,the role of PTEN in cardiac conditions such as right ventricular hypertrophy caused by chronic hypoxic pulmonary,hypertension remains unclear.This study preliminarily discussed the role of PTEN in the cardiac response to increased pulmonary vascular resistance using the hypoxia-induced PH rats.Methods Male Sprague Dawley rats were exposed to 10％ oxygen for 1,3,7,14 or 21 days to induce hypertension and right ventricular hypertrophy.Right ventricular systolic pressure was measured via catheterization.Hypertrophy index was calculated as the ratio of right ventricular mass to left ventricle plus septum mass.Tissue morphology and fibrosis were measured using hematoxylin,eosin and picrosirius red staining.The expression and phosphorylation levels of PTEN in ventricles were determined by real time PCR and Western blotting.Results Hypoxic exposure of rats resulted in pathological hypertrophy,interstitial fibrosis and remodelling of the right ventricle.The phosphorylation of PTEN increased significantly in the hypertrophic right ventricle compared to the normoxic control group.There were no changes in protein expression in either ventricle.Conclusion Hypoxia induced pulmonary hypertension developed pathological right ventricular hypertrophy and remodelling probablv related to an increased phosohorvlation of PTEN.

Influence of chronic intermittent hypoxia on growth associated protein 43 expression in the hippocampus of young rats

This study aimed to explore the pathological change to hippocampal neurons and the expression of growth associated protein 43 in 21-day-old young rats following chronic intermittent hypoxia. Hematoxylin-eosin staining results showed varying degrees of degeneration and necrosis in hippocampal neurons depending on the modeling time. Immunohistochemistry revealed that growth associated protein 43 expression in young rats following chronic intermittent hypoxia decreased, but that levels were still higher than those of normal rats at each time point, especially 4 weeks after modeling. During 1 5 weeks after modeling, a slow growth in rat weight was observed. Experimental findings indicate that chronic intermittent hypoxia may induce growth dysfunction and necrosis of hippocampal neurons, as well as increase the expression of growth associated protein 43 in young rats.

Atorvastatin Attenuates Myocardial Hypertrophy Induced by Chronic Intermittent Hypoxia In Vitro Partly through miR-31/PKCε Pathway

Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia （CIH）. However, little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy, and whether specific hypertrophyrelated microRNAs are involved in the modulation. MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia. This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy. H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days. The size of cardiomyocytes, and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR, respectively. MiR-31 mimic or Ro 31-8220, a specific inhibitor of protein kinase C epsilon （PKCε）, was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes. PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting. The results showed that CIH induced obvious enlargement of cardiomyocytes, which was paralleled with increased atrial natriuretic peptide （ANP）, brain natriuretic peptide （BNP）, and slow/beta cardiac myosin heavy-chain （MYHT） mRNA levels. All these changes were reversed by the treatment with atorvastatin. Meanwhile, miR-31 was increased by CIH in vitro. Of note, the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31. Moreover, overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes. Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.

Expression of RUNX2 and MDM21 in rats with periodontitis under chronic intermittent hypoxia

Objective: To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia. Methods: A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in each group. The molecular biological techniques of immunohistochemistry, RT-PCR and Western blotting were employed to detect the effect of different hypoxia time(0, 6, 12, 24 and 48 h) and different concentrations of hypoxia(0.000, 0.001, 0.010, 0.060 and 0.100 ppm) on the expression of RUNX2 and MDM21 in rats of four groups. Results: The expression of RUNX2 and MDM21 in each group was significantly higher than the one at other concentrations when the concentration was 0.010 ppm, with the statistical difference(P<0.05). The expression of RUNX2 and MDM21 was that normoxic control group > periodontitis group> chronic intermittent hypoxia group > compound group under the action with the concentration of 0.010 ppm for 12 h, but there was no significant difference for the comparison among groups(P>0.05). Conclusions: The condition of chronic intermittent hypoxia can reduce the expression of RUNX2 and MDM21 in rats with periodontitis and aggravate the damage of periodontal bone.

Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea（OSA）.We used a well-described OSA rat model induced with simultaneous intermittent hypoxia.Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled.The rats were exposed to intermittent hypoxia 8 hours daily for 5weeks.The changes of cardiac structure and function were examined by ultrasound.The cardiac pathology,apoptosis,and fibrosis were analyzed by H＆E staining,TUNNEL assay,and picosirius staining,respectively.The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot.Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters（LVIDs）,endsystolic volume（ESV）,end-diastolic volume（EDV）,and blood lactate level and marked reduction in ejection fraction and fractional shortening.Chronic intermittent hypoxia increased TUNNEL-positive myocytes,disrupted normal arrangement of cardiac fibers,and increased Sirius stained collagen fibers.The expression levels of hypoxia induced factor（HIF）-l α,NF-κB,IL-6,and matrix metallopeptidase 2（MMP-2） were significantly increased in the heart of rats exposed to chronic intermittent hypoxia.In conclusion,the left ventricular function was adversely affected by chronic intermittent hypoxia,which is associated with increased expression of HIF-lα and NF-κB signaling molecules and development of cardiac inflammation,apoptosis and fibrosis.

Study on Tibetan Chicken embryonic adaptability to chronic hypoxia by revealing differential gene expression in heart tissue

Oxygen concentration is essential for appropriate metabolism.Hypoxia can exert a significant impact on physiological alteration of the cell and organism.Tibetan Chicken(Gallus gallus) is a Chinese indigenous breed inhabiting in Tibetan areas,which is also a chicken breed living at high altitude for the longest time in the world.It has developed an adaptive mechanism to hypoxia,which is demonstrated by that Tibetan Chicken has much higher hatchability than low-land chicken breeds in high-altitude areas of Tibet.In the present study,Tibetan Chicken fertilized full sib eggs were incubated up to Hamburger-Hamilton stage 43 under 13% and 21% oxygen concentration,respectively.Shouguang Chicken and Dwarf Recessive White Chicken were used as control groups.The hearts in all of the 3 chicken breeds under hypoxic and normoxic conditions were isolated and hybridized to Genechip Chicken Genome Array to study molecular mechanisms underlying the adaptation to high altitude of Tibetan Chicken.As a result,50 transcripts highly expressed in hypoxia are screened out.Among up-regulated genes,some are involved in the gene ontology(GO) such as cell growth,cell difference,muscle contraction and signal transduction.However,the expression levels of 21 transcripts are lower in hypoxia than those in normoxia.Some down-regulated genes take part in cell communication,ion transport,protein amino acid phosphorylation and signal transduction.Interestingly,gene enrichment analyses of these differential gene expressions are mainly associated with immune system response and ion channel activity in response to stimulus.Moreover,the transcriptional expression profiles analyzed by hierarchical clustering and CPP-SOM software in all of the 3 different chicken breeds revealed that Tibetan Chicken is much closely related to Shouguang Chicken rather than Dwarf Recessive White Chicken.In addition,12 transcripts of Tibetan Chicken breed-specific expressed genes were identified,which seem to result in a more effective and efficient induction of energy demand and signal transduction of transcription and suppression of abnormal development in response to hypoxia.These findings will be beneficial in clarifying the adaptive molecular mechanism of Tibetan Chicken as well as providing new insight into cardiovascular disease at high altitude medicine.

Effect of NADPH Oxidase Inhibitor Apocynin on the Expression of Hypoxia-induced Factor-1α and Endothelin-1 in Rat Carotid Body Exposed to Chronic Intermittent Hypoxia

The effects of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let （HIF-lct） and endothelin-1 （ET-1） expression, elevated systolic blood pressure under chronic intermittent hypoxia （CIH） condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley （SD） male rats were randomly divided into three groups （n=10 each）： sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression of HIF-lu and ET-1 in the carotid body, and the HIF-1a protein expression was examined by using Western blotting. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1a levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apo- cynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1a and ET-1 mRNA along with HIF-la protein expression in the carotid body, and elevated circulating HIF-1a and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-lct protein expression and circulating HIF-la level in CIH-exposed animals, and there was no statistically significant difference in the HIF-lu mRNA expression between CIH group and apo- cynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1a/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for prevention and treatment of obstructive sleep apnea hypopnea syndrome-induced hypertension.

Impairment of cognitive function and reduced hippocampal cholinergic activity in a rat model of chronic intermittent hypoxia

The present study established a rat model of chronic intermittent hypoxia （CIH） to simulate obstructive sleep apnea syndrome. CIH rats were evaluated for cognitive function using the Morris water maze, and neuronal pathology in the hippocampus was observed using hematoxylin-eosin staining. In addition, hippocampal choline acetyl transferase （CHAT） and nicotinic acetylcholine receptor （nAChR） expression was determined by immunohistochemistry. Our results revealed necrotic hippocampal neurons, decreased ChAT and nAChR expression, as well as cognitive impairment in CIH rats. These results suggest that hippocampal neuronal necrosis and decreased cholinerqic activity may be involved in CIH-induced cognitive impairment in rats.

Short-term Chronic Intermittent Hypobaric Hypoxia Alters Gut Microbiota Composition in Rats

Chronic intermittent hypobaric hypoxia (CIHH) is a treatment of moderate hypoxia that simulates high altitude interrupted by normoxia. Growing evidence shows that CIHH has multiple beneficial effects on

Role of chronic hypoxia and hypoxia inducible factor in kidney disease

Cells are endowed with a defensive mechanism against hypoxia, namely hypoxia-inducible factor （HIF） andhypoxia-responsive element （HRE）. Under hypoxic conditions, activation of HIF leads to expression of a variety of adaptive genes with HRE in a coordinated manner. The amount of HIF is regulated principally by the rate of degradation through post-translational modification by prolyl hydroxylases. Experimental studies utilizing HIF stimulating agents have been effective in a variety of kidney disease models, demonstrating that the HIF-HRE pathway is a promising target of future therapeutic approaches.

Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion,have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis.Moreover,hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow,thus potentially affecting complications of cirrhosis.Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma.Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis,with a specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.Experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models.From a clinical point of view,anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.

THE PLASMA CATECHOLAMINE AND MYOCARDIAL ADRENOCEPTORS OF SUSCEPTIBLE STRAIN OF RAT DURING CHRONIC HYPOXIA

Hilltop Sprague Dawley (HT) rats were considered as a good model to investigate the mechanism of mountain sickness. They showed severe pulmonary hypertension, right ventricular hypertrophy, polycythemia and even right ventricular fail-

Changes of hypoxia-inducible factor-1 signaling and the effect of cilostazol in chronic cerebral ischemia

Hypoxiainducible factor1 and its specific target gene heme oxygenase1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hy poxiainducible factor1/heme oxygenase1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol （30 mg/kg） for 9 weeks. Morris water maze results showed that cognitive impairment gradually worsened as the cerebral ischemia proceeded. Immunohistochemistry, semiquantitative PCR and western blot analysis showed that hypoxiainducible factorla and heme oxygenase1 expression levels in creased after chronic cerebral ischemia, with hypoxiainducible factorla expression peaking at 3 weeks and heme oxygenase1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxiainducible factorla may upregulate heine oxygenase1 expression fol lowing chronic cerebral ischemia and that the hypoxiainducible factor1/heme oxygenase1 sig naling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, decreased hypoxiainducible factorla and heme oxygenase1 expression levels, and reduced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an antiapoptotic mechanism.

布地奈德雾化吸入配合无创机械通气治疗老年慢性阻塞性肺疾病并发呼吸衰竭的疗效研究

目的 探究布地奈德雾化吸入配合无创机械通气治疗慢性阻塞性肺疾病(COPD)并发呼吸衰竭的老年患者的临床效果。方法 选取2022年2月至2023年2月首都医科大学附属北京友谊医院收治的82例COPD并发呼吸衰竭的老年患者82例,采用随机数字表法分为对照组和观察组,每组41例。对照组接受无创机械通气治疗,观察组在对照组治疗的基础上给予布地奈德(2 mg/次,2次/d)雾化吸入治疗,两组患者均治疗1周。比较两组治疗前后的肺功能、血气指标、生命体征指标、临床症状评分及血清低氧诱导因子-1α、血清淀粉样蛋白A水平,并比较两组治疗后的临床疗效。结果 治疗1周后,两组患者的肺功能指标(用力肺活量、第1秒用力呼气容积、第1秒用力呼气容积与用力肺活量的比值、呼气峰值流速占正常预计值的百分比和6分钟步行试验距离)、动脉血氧分压、血氧饱和度、pH均高于治疗前,且观察组均高于对照组,差异有统计学意义(P<0.05),而呼吸频率、心率、动脉血二氧化碳分压、血清低氧诱导因子-1α、血清淀粉样蛋白A水平和临床症状评分均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。观察组临床总有效率为85.37%,明显高于对照组的73.17%,但差异无统计学意义(P>0.05)。结论 布地奈德雾化吸入配合无创机械通气治疗可有效提高COPD并发呼吸衰竭老年患者的肺功能,改善动脉血气、生命体征和临床症状,减轻机体的氧化应激和炎症反应,值得临床使用。

大鼠颈上神经节中Ⅰ组代谢型谷氨酸受体表达及慢性间歇性低氧对其的影响

目的观察Ⅰ组代谢型谷氨酸受体(mGluR1/5)在大鼠颈上神经节(SCG)组织的表达、定位,及慢性间歇性低氧(CIH)对mGluR1/5蛋白水平的影响。方法12只雄性SD大鼠随机分为对照组(Ctrl)和CIH组(CIH),每组6只,模型制作6周。Western blotting检测CIH对mGluR1/5蛋白水平的影响,免疫组织化学法和免疫荧光共定位染色检测大鼠SCG中mGluR1/5的表达及分布。结果mGluR1/5表达于大鼠SCG,mGluR1分布于神经元和小强荧光(SIF)细胞,而在卫星胶质细胞(SGCs)、神经纤维和血管不表达;mGluR5主要分布于神经纤维,少量分布于神经元,而在SIF细胞、SGCs及血管不表达;CIH上调mGluR1/5的蛋白水平(P<0.01)。结论mGluR1和mGluR5均表达于大鼠SCG,但其表达部位有所不同,两者蛋白水平的升高可能参与了CIH诱导的血压升高。

抑制髓样细胞触发受体-1(TREM-1)减轻慢性间歇性低氧诱发的模型小鼠动脉粥样硬化

目的探究髓样细胞触发受体-1(TREM-1)在慢性间歇性低氧(CIH)诱发的动脉粥样硬化(AS)中作用。方法将ApoE-/-小鼠随机分为空白组、模型组和实验组。模型组和实验组小鼠饲养于低氧环境,给予高脂饲料喂养;实验组小鼠高脂饲养4周后,腹腔注射TREM-1抑制剂LR12(5 mg/kg),连续干预8周。饲养12周后,检测血清总胆固醇(TC)、低密度脂蛋白(LDL)、三酰甘油(TG)、肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1β)、白细胞介素10(IL-10)水平;组织学分析主动脉TREM-1表达、斑块面积及巨噬细胞水平。结果与空白组相比,模型组小鼠主动脉TREM-1表达量显著升高(P<0.05)。相比于模型组,实验组小鼠主动脉斑块显著减少,血清血脂(TC、LDL、TG)及炎性因子(TNF-α、IL-1β、IL-10)水平显著降低,主动脉斑块及斑块浸润巨噬细胞、TREM-1表达显著减少(P<0.05),且斑块中TREM-1表达与巨噬细胞为共定位。结论TREM-1参与CIH诱发的AS发生发展,抑制TREM-1能够减轻CIH诱发的AS,其机制与抑制巨噬细胞活化有关。