fenofibrate在缺血再灌注中的作用研究

fenofibrate是降脂药fibrate家族中的一种药物,目前主要临床应用是降低血胆固醇水平[1]。作为PPAR-α的激动剂,fenofibrate以转录因子的角色参与基因表达,调节细胞内糖类和脂肪代谢以及脂肪组织分化[2]。最近研究发现,除了降低血脂以外,fenofibrate还通过抗氧化应激和抗炎,在缺血再灌注模型中发挥减轻损伤的作用。本文就fenofibrate在抗氧化抗炎和缺血再灌注中的研究做一综述。

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is a common health problem with a high mortality burden due to its liver- and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus(T2DM) and metabolic syndrome(MetS).Impaired hepatic fatty acid(FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors(PPARs)are involved in lipid and glucose metabolic pathways.The novel concept is that the activation of the PPARαsubunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis.These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet,T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent.In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

Fenofibrate Pre-treatment Suppressed Inflammation by Activating Phosphoinositide 3 Kinase/Protein Kinase B(PI3K/Akt) Signaling in Renal Ischemia-Reperfusion Injury

The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury（IRI） in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups： sham-operated group（sham）, IRI＋saline group（IRI group）, IRI＋Fenofibrate（FEN） group. Normal saline or Fenofibrate（3 mg/kg） was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8（IL-8）, tumor necrosis factor alpha（TNF-α） and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B（PI3K/Akt） signaling and peroxisome proliferator-activated receptor-α（PPAR-α） were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.

Inhibitory Effects of Fenofibrate on Plasminogen Activator Inhibitor-1 Expression in Human Endothelial Cells

The effects of fenofibrate on plasminogen activator inhibitor-1 （PAI-1） expression in human umbilical endothelial cell-derived transformed cell line--ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate （0, 10, 50, 100 μmol/L） for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction （RT-PCR） and Western blot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate （10 pmol/L）, the expression levels of PAI-1 mRNA and protein were 0. 65±0.05 and 0.96± 0. 11 respectively, significantly lower than in the control group （0.78±0.03 and 1.21±0.15, respectively, P〈0.05）. PAI-1 antigenic contents （24.52±8.39） in ECV304 cells treated with 10 μmol/L fenofibrate were significantly lower than those in the control group （6.98±5.12, P〈0.05）. It was concluded that fenofibrate inhibited the expression of PAF1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.

Preparation and pharmacokinetic study of fenofibrate cubic liquid crystalline

An LCC delivery system for Fenofibrate (Fen) was developed to improve its poorly oral bioavailability. Fen-LCC preparation methods were screened, and the prepared Fen-LCC was then characterized by a polarizing microscope and transmission electron microscopy (TEM).The spray drying technique was selected to dry and solidify particles into powder. The in vitro release of Fen-LCC was measured and in vivo pharmacokinetic experiments were carried out on rats after oral administration. Particles prepared through the high-temperature input method exhibited structural characteristics of LCC, and re-dissolved particles maintained the same features. The LCC delivery system can significantly improve in vitro release outcomes. After oral administration, AUCs of the suspension and LCC systems were measured at 131.6853 μg·h/ml and 1435.72893 μg·h/ml, respectively. The spray drying process presented here better maintains cubic structures, and the LCC system significantly improves bioavailability levels.

Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry （DSC） shows that the aforesaid active pharmaceutical ingredient （API） is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy （BDS） covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were per- formed after its vitrification by fast cooling from a few degrees above the melting point （Tm=354.11 K） to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel- Fulcher-Tamman （VFT） equation. From VFT fit, glass transition temperature （Tg） was estimated as 250.56 K and fragility （m） was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch-Williams-Watts （KWW） fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai＇s coupling model, we identified the excess wing as true Johari-Goldstein （JG） process. Below the glass transition temperature one can clearly see a secondary relaxation （γ） with an activation energy of 32.67 kJ/mol.

Biopsy-confirmed fenofibrate-induced severe jaundice:A case report

BACKGROUND Drug-induced liver injury(DILI)is the leading cause of acute liver failure in the United States.DILI is mainly caused by painkillers and fever reducers,and it is often characterized by the type of hepatic injury(hepatocellular or cholestatic).This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease.We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases.CASE SUMMARY A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test.Abdominal ultrasound and computed tomography showed no biliary obstruction or nonspecific findings in the liver.Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis.Following the biopsy,steroid therapy was initiated and after 3 wk of treatment,the total bilirubin level was reduced to 7.22 mg/dL.CONCLUSION In patients with hyperlipidemia,treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis,warranting clinical attention.

Fenofibrate for the prevention of progression of non-proliferative diabetic retinopathy:review,consensus recommendations and guidance for clinical practice

The prevalence of diabetic retinopathy(DR),and associated morbidity is high in the Asia-Pacific region.Emerging evidence suggests a potential role for fenofibrate in the prevention of progression of DR,especially in patients with cardiovascular risk,and pre-existing mild-to-moderate DR.Fenofibrate has also been found to reduce maculopathy,and the need for laser treatment in these patients.Considering these benefits of fenofibrate,a group of experts from the fields of endocrinology and ophthalmology convened in May 2017,to discuss on the the mechanism of action,and clinical efficacy of fenofibrate in DR.The findings from key clinical studies on fenofibrate in DR were reviewed by the experts,and consensus statements were derived to define the role of fenofibrate in the prevention and treatment of DR.The statements were rated based on the GRADE criteria.An algorithm was also developed for the screening and treatment of DR in patients with type 2 diabetes(T2D),and the place of fenofibrate was defined in the algorithm.The expert recommendations,and the algorithm provided in this review will serve as a guide to the clinicians to reconsider the adjunctive use of fenofibrate for preventing the progression of DR in selected T2D patients.

Dissolution improvement of fenofibrate by melting inclusion in mesoporous silica

In this study,using mesoporous silica for the solubility enhancement of poorly watersoluble drug was investigated.Although the incorporating drug into mesoporous silica is generally performed through the solvent method,the new melting method was proposed in the present study.Fenofibrate,a poorly water-soluble drug,was incorporated into mesoporous silica by solvent method and melting method.The obtained samples were observed by SEM and their physicochemical properties were evaluated by PXRD and DSC measurement.The dissolution and supersaturated property were also investigated.The results from SEM,PXRD and DSC measurement showed that drug could be loaded into pore via the melting method as well as by the solvent method.The drug loaded quantity depended on the pore volume.Drug up to 33%could be incorporated into mesoporous silica and existed in amorphous state.When drug was overloaded or difficulty in incorporation into pore was found,recrystallization of drug occurred at the outer surface of mesoporous silica.From the dissolution test,samples prepared by solvent method and melting method gave the supersaturated drug concentration which sample from melting method showed superior dissolution to the one from solvent method.From this study,drug was efficiently incorporated into mesoporous silica by the melting method which is a simple and solvent-free process,and the aqueous solubility enhancement of poorly watersoluble drug was achieved.

Clinical research of fenofibrate and spironolactone for acute central serous chorioretinopathy

AIM：To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy（CSCR）.METHODS： Totally 60 patients（60 eyes） with a history of acute CSCR were randomed into two groups： group A with combination of fenofibrate（200 mg） and spironolactone（100 mg）,and group B with only fenofibrate（200 mg）.They were taken half an hour before meals and once per day for 8wk.The changes of the visual acuity,subjective symptom,ocular surface disease index（OSDI）,the tear film and optical coherence tomography were observed at 2,4,6,and 8wk before and after treatment.RESULTS： The best corrected visual acuity（BCVA,log MAR） was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B（P 〈0.05）,respectively.After 8wk treatment,the central subfield thickness（CST）,and subretinal fluid volumn（SFV） decreased significantly to 49.5% and 78.8% in group A,37.0% and 57.2% in group B.There were significant differences of CST and SFV in both groups（all P 〈0.05）.CONCLUSION：Fenofibratecombinedwithspironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.

Determination of Fenofibrate and the Degradation Product Using Simultaneous UV-Derivative Spectrometric Method and HPLC

Two new selective, precise, and accurate methods were developed for the determination of fenofibrate in the presence of its basic degradation product. In the first method fenofibrate was determined using an algorithm bivariate calibration derivative method, in which an optimum pair of wavelengths was chosen for the determination of different binary mixtures. In the second method (HPLC), separation was achieved on RESTEK Pinnacle II phenyl column (5 μm, 250 × 4.6 mm) and Pinnacle II phenyl (5 μm, 10 × 4 mm) guard cartridge using a mobile phase consisting of methanol –0.1% phosphoric acid (60:40, v/v) at a flow rate 2 mL●min–1, and the column oven temperature was set at 50°C. The UV detector was time programmed at 302 nm and 289 nm for the internal standard (I.S.) and fenofibrate, respectively. The proposed methods were successfully applied for the determination of fenofibrate and its degradation product in the laboratory-prepared mixture and in pharmaceutical formulation. The assay results obtained using the bivariate method were statistically compared to those of the HPLC method and good agreement was observed.

Formulation and Characterization of Fenofibrate Loaded Solid Dispersion with Enhanced Dissolution Profile

Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability). Its bioavailability is limited by the dissolution rate. This study was aimed to enhance the rate of dissolution of poorly water soluble drug, FF. Initially, solid dispersions of fenofibrate (SDFs) were formulated with Carplex-80 or PEG-4000 or in combination at various weight ratios and were subjected to dissolution study. On the basis of drug release at various time intervals, the formulation producing maximum drug concentration was evaluated physicochemically using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). It was observed that the peak drug concentration was obtained at 120 min of dissolution by formulation SDF-7, which contains a mixture of Carplex-80 and PEG-4000 at weight ratio 1:5:6 of FF:PEG-4000:Carplex-80, respectively. Thus, the extent of drug release by SDF-7 was maximized by 2.5-fold than that of pure FF. Physicochemical characterization revealed the reason for this increased drug release as a conversion of crystalline FF to amorphous form and ensured the chemical compatibility among FF and carriers. The results specified the significant improvement of FF release using solid dispersion technique.

Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistance of toxic cholestasis.

Spray drying of fenofibrate loaded nanostructured lipid carriers

The conversion of aqueous dispersion of nanostructured lipid carriers(NLCs) into dry powder by spray drying could be a useful approach to render NLCs with better physical chemical stability than the aqueous dispersion. In this study, aqueous NLC dispersion containing fenofibrate was converted into dry, easily reconstitutable powder using spray drying. A central composite face centered design(CCFD) was used to investigate the influence of the ratio of lipid to protectant(mannitol and trehalose) and crystallinity of spray-dried powder on the particle size, yield and residual moisture content of the dried powder. A linear relationship(R2= 0.9915) was established between the crystalline content of the spray-dried powders against the ratio of mannitol to trehalose from 3:7 to 10:0(w/w). Spray drying of NLC aqueous dispersion using a mannitol and trehalose mixture resulted in an increase in particle size of the NLCs after reconstitution in water as compared to that in the initial aqueous dispersion. The decrease in crystallinity of the dry powder by reducing the ratio of mannitol to trehalose could improve the reconstitution of the NLCs in water. However the yield and residual moisture content of dry powder decreased with an increase in the ratio of mannitol to trehalose. Lipid nanoparticles were able to retain the drug incorporation and the prolonged drug release profile after spray drying. The experimental model was robust, and suggested that spray drying is a viable technique for the conversion of NLCs into dry powder.

Prevalence of Dyslipidemia among Patients Received at the Biochemistry Unit of the Charles de Gaulle Pediatric University Hospital in Ouagadougou

Introduction: Cardiovascular disease represents a major public health burden worldwide. Research and management of risk factors contribute to the prevention of these diseases. The aim of this study was to assess the prevalence of dyslipidemia in the biochemistry unit of the Charles De Gaulle Pediatric University Hospital (CHUP-CDG) in Ouagadougou. Material and Methods: This was a descriptive and analytical cross-sectional study, with retrospective data collection from January 1, 2020 to December 31, 2022. Patients of all ages who performed a lipid panel in the CHUP-CDG biochemistry unit during the study period have been included. Results: A total of 2872 patients have been included. The mean age of the study population was 27.72 ± 19.51 years and the M/F sex ratio was 0.81. Among the patients, 22.84% had at least one dyslipidemia. The prevalences of hypercholesterolemia, hypo-HDL cholesterolemia and hyper-LDL cholesterolemia were 11.57%, 49.19% and 57.50% respectively. Hypertriglyceridemia and mixed hyperlipidemia were present in 9.04% and 2.08% of patients. Hypercholesterolemia was significantly more frequent in the female sex (p = 0.0077);hyper-LDL cholesterolemia (p = 0.0255) and mixed hyperlipidemia (p Conclusion: The relatively high prevalence of dyslipidemia in the study indicates a worrying situation. It would therefore appear essential to extend the search for risk factors nationwide, particularly those that can be modified, in order to reduce morbidity and mortality linked to cardiovascular disease.

Dyslipidemia in Adults with Type 2 Diabetes in a Rural Community in Ganadougou, Mali: A Cross-Sectional Study

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Fenofibrate可减缓糖尿病患者的病情进展

法国Fournier制药公司的Jean-Claude Ansquer。博士及其同事报道说，fenofibrate(非诺贝特，FB)与2型糖尿病患者的脂类改善及微白蛋白尿症进展的减缓关联；但还需更进一步的研究以确定其对肾功能的长期作用。

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Analysis of the Mechanism of Intervention of Fangxiangxiaozhi Prescription on Dyslipidemia Based on Network Pharmacology and Molecular Docking

Objective: To explore the mechanism of intervention of Fangxiangxiaozhi prescription on dyslipidemia by using network pharmacology and molecular docking. Methods: The traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pubchem, Uniprot, and other databases were adopted to screen the active ingredients and the corresponding targets of Fangxiangxiaozhi prescription. Dyslipidemia-related targets were identified using the databases of Disgenet and GeneCards. Then, the intersection target of drugs and diseases was demonstrated via a Venn diagram. Cytoscape3.7.2 was used to construct a “drugs-active ingredients-intersection targets” network map and the key active ingredients with the top 7-degree values were determined. The protein interaction network and topology analysis of the intersection target genes were carried out by combining STRING11.0 and Cytoscape3.7.2. Moreover, the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the intersection target genes were carried out using the Metascape database. Lastly, the key active ingredients and targets were molecular docked by AutoDockTools, Pymol, and other software. Results: There were 51 active components and 509 target genes of which 74 intersect with dyslipidemia. The key targets included tumor necrosis factor (TNF), interleukin-6 (IL-6), AKT1, PPAR gamma (PPARG), VEGFA, and PPARα. GO enrichment analysis obtained 1040 biological processes, 33 cell components, and 84 molecular functions;KEGG enrichment analysis obtained 148 pathways. The molecular docking results showed that the key targets and compounds exhibited good binding force. Conclusion: The active ingredients of Fangxiangxiaozhi prescription regulated several pathways through multiple targets to intervene in dyslipidemia. This study can serve as a foundation for further research.

残余胆固醇与进展为主要不良心血管事件的非罪犯病变易损斑块的相关性研究

背景 残余胆固醇(RC)被认为是动脉粥样硬化性心血管疾病的重要危险因素,而冠状动脉非罪犯病变(NCCLs)进展也是影响冠心病患者预后的重要因素,但是残余胆固醇与进展为主要不良心血管事件(MACE)的NCCLs易损斑块的关系尚不明确。目的 探讨RC对发生MACE的NCCLs易损斑块的预测价值及长期预后的相关性。方法 选取2015年2月—2022年2月于新疆医科大学第一附属医院心脏中心住院的488例冠心病患者为研究对象,通过电子病历系统收集患者基线资料,行冠状动脉造影及光学相干断层扫描OCT。入组患者在出院1、3、6和12个月接受预定随访。采用Spearman秩相关检验探究RC与NCCLs中薄纤维帽粥样硬化斑块(TCFA)斑块特征的相关性。采用多因素Logistic回归分析探究NCCLs中TCFA发生MACE的影响因素。绘制受试者工作特征曲线(ROC曲线)并计算ROC曲线下面积(AUC),探究RC对NCCLs中TCFA发生MACE的预测价值。结果 共纳入488例冠心病患者,根据NCCLs是否发生MACE将患者分为发生MACE组(n=38)和未发生MACE组(n=450)。通过OCT识别NCCLs的斑块特征,共分析了749个NCCLs斑块,304个NCCLs斑块最小管腔面积(MLA)<3.5 mm^(2)。随访期间38例(7.8%)患者共发生了41例次NCCLs斑块引起的MACE事件,18例(3.7%)患者发生了支架内再狭窄,15例(3.1%)发生了不确定因素的死亡。发生MACE组患者高血压、糖尿病、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、RC、糖化血红蛋白(Hb A1c)、TCFA、MLA<3.5 mm^(2)比例高于未发生MACE组(P<0.05)。105例患者检查出TCFA,其中22例发生MACE(发生MACE的TCFA组),83例未发生MACE(未发生MACE的TCFA组)。发生MACE的TCFA组糖尿病比例与RC高于未发生MACE的TCFA组(P<0.05)。Spearman秩相关分析结果示,RC与最薄纤维帽厚度、MLA呈负相关(r_(s)=-0.665、-0.771,P<0.05),与最大脂质弧度、巨噬细胞浸润呈正相关(r_(s)=0.806、0.481,P<0.05)。多因素Logistic回归分析结果显示糖尿病(OR=3.410,95%CI=1.165~9.988,P=0.025)、高RC水平(OR=5.879,95%CI=1.436~24.073,P=0.014)是NCCLs中TCFA发生MACE的危险因素。绘制RC预测NCCLs中TCFA发生MACE的ROC曲线,结果显示AUC为0.695(95%CI=0.571~0.819,P=0.005),最佳截断值为0.606 mmol/L,灵敏度、特异度分别为0.818、0.518。结论 RC水平升高可能是冠心病患者中NCCLs易损斑块发生MACE的危险因素,对NCCLs中TCFA发生MACE有一定的预测价值。