食管癌组织中Krüppel-like Factor4表达与术后复发转移的相关性

目的探究食管癌组织中Krüppel-like Factor4表达与术后复发转移的相关性。方法选取食管癌患者160例并收集其临床资料。采取免疫组化法检测Krüppel-like Factor4表达,根据患者术后是否复发转移将其分为复发转移组和无复发转移组,对比Krüppel-like Factor 4表达水平,并采用多因素logistic回归分析食管癌切除术患者术后复发转移的危险因素。结果Krüppel-like Factor4蛋白表达与分化程度、临床分期和淋巴结转移等临床病理参数显著相关(P<0.05),与患者的年龄、性别、肿瘤直径均无相关性(P>0.05)。复发转移组术后Krüppel-like Factor4阳性表达率显著低于未复发转移组,差异有统计学意义(P<0.05)。多因素分析显示,Krüppel-like Factor4(OR=2.012,P<0.001)是食管癌术后发生复发转移的独立影响因素。结论食管癌组织中Krüppel-like Factor4表达与患者术后复发转移具有相关性,其对患者术后复发转移具有重要预测价值。

Krüppel-like factor 4慢病毒表达载体构建及其对胃癌细胞BGC-823生物学行为的影响

目的构建Krüppel-like factor4(KLF4)过表达慢病毒载体,探讨其对胃癌细胞株BGC-823生物学行为的影响。方法检测BGC-823中KLF4 mRNA的表达水平;用真核表达质粒pcDNA3.1IE-KLF4-EGFP,将KLF4基因连入慢病毒载体pLv-UbC-IRES2-EGFP中,构建pLv-KLF4-IRES2-EGFP重组慢病毒表达载体。将酶切和测序鉴定后的重组质粒转染至BGC-823中,观察转染情况,RT-PCR检测KLF4 mRNA。慢病毒包装后转染BGC-823细胞,Western印迹检测KLF4蛋白。结果重组质粒经酶切和DNA测序证实目的基因插入正确;pcDNA3.1IE-KLF4-EGFP转染BGC-823细胞后KLF4 mRNA升高。慢病毒包装后转染BGC-823检测到目的蛋白KLF4。KLF4能够将细胞阻滞于G1/S,抑制其生长、促进细胞凋亡,减少细胞侵袭能力。结论转染BGC-823后KLF4蛋白检测证实慢病毒载体成功构建,KLF4能抑制胃癌细胞的恶性转化。

Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer

AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.

Correlation of Krüppel-like factor 9 expression in pancreatic cancer tissue with serum tumor markers and focal cell invasion

Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.

Krüppel-like factor 8 is a potential prognostic factor for pancreatic cancer

Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been found to be deregulated in multiple cancers,and its high expression was correlated with poor prognosis.However,so far,no information was reported about the expression of KLF8 in pancreatic cancer.In the present study,we investigated,possibly for the first time,the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival （OS） rate.Methods We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics.We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time.Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.Results KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9％ of the 68 cases had positive expression.KLF8 expression was not associated with sex,age,tumor location,lymph node stage,and metastasis stage,but was associated with tumor stage （P=0.04）.Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis.In univariate and multivariate models,KLF8 was a significant predictor of OS in pancreatic cancer.Conclusion Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.

Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies

Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.

Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

利用数字化仪实现放射性气体85Kr核素活度浓度的绝对测量

基于中国计量科学研究院建立的长度补偿法充气正比计数器绝对测量系统,利用CAEN公司开发的DT5730型数字化仪替代多套传统模拟电子学插件,并通过数字化仪对β信号进行采集、重建和数据离线分析,开展85Kr放射性惰性气体活度浓度的绝对测量。实验研究了各种条件的影响,通过对正比计数器端效应、正比计数器壁效应、本底、噪声、死时间漏计数和阈值以下计数进行修正,最终得到85Kr活度浓度绝对测量结果。在相同阈值、主放大倍数100倍、气压50.5 kPa,工作电压1675 V和1700 V的条件下,数字化仪测量和电子学插件测量^(85)Kr放射性活度浓度的相对偏差分别为0.83%和0.74%。测量结果在不确定度范围内一致,证明数字化仪可有效替代传统电子学插件实现放射性惰性气体^(85)Kr活度浓度的绝对测量。

Genetic Predisposition for Type 2 Diabetes Mellitus in a Cameroonian Population: Contribution of rs4731702 (C/T) Polymorphism of Krüppel-Like Factor 14 Gene

Introduction: Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. Patients and Methods: This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. Conclusion: This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.

急性缺血性脑卒中患者血清微小RNA-140-3p、Krüpple样因子5表达水平与颈动脉斑块稳定性及狭窄程度的相关性

目的探索急性缺血性脑卒中(AIS)患者血清微小RNA-140-3p(miR-140-3p)、Krüpple样因子5(KLF5)表达水平与颈动脉斑块稳定性及狭窄程度的相关性。方法选择2022年10月—2024年1月本院收治的285例AIS患者作为研究对象,依据超声结果将患者分为斑块易损组(196例)、斑块稳定组(53例)以及无斑块组(36例);将患者依据斑块狭窄程度分为狭窄重度组(42例)、狭窄中度组(57例)、狭窄轻度组(150例)以及无狭窄组(36例)。收集患者的一般资料,采用实时荧光定量PCR对血清miR-140-3p、KLF5表达水平进行检测;多因素Logistic回归分析AIS患者颈动脉斑块不稳定性的影响因素;受试者工作特征(ROC)曲线分析血清miR-140-3p、KLF5水平检测对AIS患者颈动脉斑块不稳定的诊断价值;分析不同狭窄程度血清miR-140-3p、KLF5水平;Pearson法和Spearman法相关性分析血清miR-140-3p、KLF5水平的相关性及二者与AIS患者颈动脉斑块稳定及狭窄程度的相关性。结果斑块易损组患者高血压人数、糖尿病人数、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(LDL-C)、D-二聚体(D-D)、纤维蛋白原(FIB)、膀抑素C(Cys-C)及KLF5水平高于斑块稳定组及无斑块组(P<0.05),血小板(PLT)及miR-140-3p水平低于斑块稳定组及无斑块组(P<0.05),斑块稳定组LDL-C、FIB、D-D、Cys-C及KLF5水平高于无斑块组(P<0.05),PLT及miR-140-3p水平低于无斑块组(P<0.05);多因素Logistic回归分析显示PLT、D-D、FIB、Cys-C、miR-140-3p、KLF5是AIS患者斑块不稳定性的影响因素(P<0.05);ROC分析显示,miR-140-3p、KLF5联合诊断AIS患者颈动脉斑块不稳定的ROC曲线下面积(AUC)显著大于miR-140-3p单独诊断的AUC(Z=4.617,P<0.001),KLF5单独诊断的AUC(Z=3.473,P=0.001);随着患者狭窄程度的增加,患者血清miR-140-3p水平降低(F=341.819,P<0.001),血清KLF5水平升高(F=152.186,P<0.001);Pearson法相关性分析显示,血清miR-140-3p水平与血清KLF5水平及斑块稳定性、狭窄程度呈负相关(r=-0.536,-0.529,-0.601,P<0.001),血清KLF5水平与斑块稳定性及狭窄程度呈正相关(r=0.511,0.634,P<0.001)。结论AIS患者血清miR-140-3p水平降低,血清KLF5水平升高,其水平变化与颈动脉斑块稳定性及狭窄程度密切相关。

基于改进CNN-LSTM和RF的铁水KR脱硫预测模型

为实现较高精度的脱硫剂加入量预测,有效提高生产效益,本文提出一种基于改进卷积神经网络(CNN)-长短期记忆(LSTM)网络和随机森林(RF)结合的铁水脱硫两步预测模型。考虑到模型输入数据的相关性,利用皮尔逊相关系数确定各输入参数的相关性并筛选特征。模型以CNN-LSTM为基础,增加卷积层和残差连接,在提高挖掘数据的高维特征信息的同时避免网络退化。为增加网络对特征的区分和关注能力,引入多头注意力机制,让网络更加关注特征中的重要信息。使用贝叶斯优化RF超参数构建误差预测模型从而实现残差推理,对改进的CNN-LSTM模型预测结果进行修正。以现场采集的数据进行实验,结果表明,与CNN-LSTM模型相比,本文模型的拟合精度R2提升了17.11%,平均绝对值误差MAE降低了24.85%,均方根误差RMSE降低了30.18%,平均绝对百分比误差MAPE降低了28.33%。

静态法和动态法评价活性炭分离低浓度Xe和Kr的性能

为获得高比活度的Xe测量源,开展了常温常压下CF-1450活性炭分离低浓度Xe和Kr的研究。利用液氮温度下N2的吸附脱附测试对CF-1450活性炭的孔结构进行了表征。结果表明,CF-1450活性炭的BET比表面积为1680 m^(2)/g,孔径分布以微孔为主。采用静态吸附法和混合气体动态吸附-脱附法研究了CF-1450活性炭常温常压下分离低浓度Xe和Kr的性能。在25℃时,CF-1450活性炭的Xe静态吸附容量为3.25 mmol/g,Kr静态吸附容量为1.30 mmol/g;Xe亨利系数为0.21 mmol/(g·kPa),Kr亨利系数为0.02 mmol/(g·kPa),Xe/Kr亨利选择性为10.5。在低压下,利用IAST法计算的Xe/Kr吸附选择性(y(Xe)∶y(Kr)=50∶50,y为混合气体中Xe、Kr的摩尔分数)为10.6。CF-1450活性炭对Xe和Kr的零点等量吸附热分别为35.7 kJ/mol和13.9 kJ/mol。基于CF-1450活性炭动态吸附分离和动态脱附分离低浓度Xe和Kr的研究结果,建立了常温常压下动态吸附-脱附法分离低浓度Xe和Kr的工艺流程,Xe回收率为79%,Kr去污因子为195。

铁水KR脱硫搅拌器新型连接方式设计及应用

针对KR脱硫搅拌器拆卸时间长的技术难题,提出了将搅拌器连接方式由8个螺栓更换为2个螺栓加上6个销轴的新方式,并校核了两种连接方式下的零部件强度,确认了改进方式的可行性。新连接方式上线应用后,搅拌器的拆卸时间降低了74.3%,成效显著。

首钢京唐KR热态脱硫渣重复利用的应用

以京唐KR热态脱硫渣重复利用项目为依托,对KR热态脱硫渣重复利用技术及设备进行研究,开发出具有自主知识产权的KR热态脱硫渣重复利用装置,并成功应用于实际生产,取得了良好的应用效果。

熔融制样-X射线荧光光谱法测定KR脱硫剂中氧化钙、氧化镁和二氧化硅含量的研究

目前对于KR脱硫剂中氧化钙、氧化镁和二氧化硅含量的测定采用络合滴定法和分光光度法进行分析。上述方法存在周期较长、操作繁琐、检测过程须接触危险化学品、产生废液等缺点。采用灼烧减量、熔融制样,X射线荧光光谱法测定KR脱硫剂中氧化钙、氧化镁和二氧化硅含量简单快速、具有较好的精密度、准确度,缩短了检验周期,大幅提高了检验效率。

冠心病患者血清Krüppel样因子5和7表达水平及其与冠脉病变程度关系研究

目的:探究冠心病(CAD)患者血清Krüppel样因子5(KLF5)和Krüppel样因子7(KLF7)表达水平及其与冠脉病变程度的关系。方法:选取进行冠脉造影检查的CAD患者183例,根据冠脉造影结果分为CAD组(98例)和对照组(85例),又根据Genisini评分将CAD患者分为轻度病变组(56例)和重度病变组(42例)。酶联免疫吸附法(ELISA)检测患者肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)、KLF5、KLF7水平。全自动生化仪检测高密度脂蛋白胆固醇(HDL-C)、肌酐(Cr)、低密度脂蛋白胆固醇(LDL-C)、血尿酸(BUA)、三酰甘油(TG)以及总胆固醇(TC)水平。Pearson法分析重度病变组KLF5、KLF7水平的相关性。受试者工作特征(ROC)曲线分析KLF5、KLF7对CAD患者发生重度病变的诊断价值。结果:CAD组血清TNF-α、CRP、BUA、LDL-C、TG、TC、Cr、KLF5、KLF7表达高于对照组,HDL-C水平低于对照组(均P<0.05)。重度病变组BUA、Cr、KLF5、KLF7水平高于轻度病变组(均P<0.05)。KLF5、KLF7水平高是CAD患者发生重度冠脉病变的独立危险因素(均P<0.05)。重度病变组KLF5和KLF7水平呈正相关(r=0.427,P=0.000)。血清KLF5、KLF7诊断CAD患者发生重度病变的曲线下面积(AUC)分别为0.823、0.810,两者联合诊断的AUC为0.907,优于各自单独诊断(均P<0.05)。结论:CAD患者血清KLF5、KLF7水平越高,冠脉病变程度越高,两者诊断CAD患者发生重度病变具有较高的价值。

Krüppel样转录因子在糖尿病肾病中的作用机制

Krüppel样转录因子(Krüppel-like transcription factor,KLF)是一类含有锌指结构的转录因子,参与基因表达的调控过程,在多种疾病中表达异常。在糖尿病肾病(diabetic kidney disease,DKD)中,KLF通过调控细胞凋亡、炎症反应、线粒体自噬、细胞脂毒性和纤维化等过程发挥重要作用。本文就KLF家族在DKD中的研究进展进行综述,为今后DKD的预防和治疗提供新的靶点和理论依据。

血清Krüppel样因子2和血管紧张素Ⅱ受体样1内源性配体13对血液透析患者自体动静脉内瘘狭窄的预测价值

目的探讨血清Krüppel样因子2(KLF2)、血管紧张素Ⅱ受体样1内源性配体13(Apelin-13)水平对血液透析患者自体动静脉内瘘(AVF)狭窄的预测价值。方法选取2018年6月至2022年12月山东省济南市人民医院收治的214例以AVF为血管通路的血液透析患者为血液透析组,另选取同期53例体检健康者为对照组。血液透析组患者根据是否伴有AVF狭窄分为狭窄组(37例)和非狭窄组(177例)。记录患者临床资料,采用酶联免疫吸附试验法检测血清KLF2、Apelin-13水平。通过多因素Logistic回归方法分析血液透析患者AVF狭窄的影响因素,采用受试者工作特征(ROC)曲线分析血清KLF2、Apelin-13水平对血液透析患者AVF狭窄的预测价值。结果血液透析组血清KLF2、Apelin-13水平均低于对照组(均P<0.001)。狭窄组年龄、透析龄、透析中低血压比例、超滤率、低密度脂蛋白胆固醇水平均大于/长于/高于非狭窄组,体重指数、收缩压、KLF2、Apelin-13水平均低于非狭窄组(均P<0.05)。多因素Logistic回归分析结果显示,透析龄延长、透析中低血压、超滤率增加为血液透析患者AVF狭窄的独立危险因素,体重指数增加、KLF2升高、Apelin-13升高为独立保护因素(均P<0.05)。ROC曲线分析结果显示,血清KLF2、Apelin-13单独与联合预测血液透析患者AVF狭窄的曲线下面积分别为0.797、0.794、0.907,敏感度分别为54.05%、100.00%、91.89%,特异度分别为92.66%、50.85%、83.05%。结论血清KLF2、Apelin-13水平降低与血液透析患者AVF狭窄密切相关,可作为AVF狭窄的辅助预测指标。

Krüppel样转录因子8与乳腺癌他莫昔芬耐药的相关性

目的:探讨Krüppel样转录因子8(KLF8)与乳腺癌他莫昔芬(TAM)耐药及预后的相关性。方法:利用公共数据库分析KLF8 mRNA在TAM敏感与耐药细胞中的表达差异及KLF8 mRNA对接受TAM治疗乳腺癌患者预后的影响。运用RT-PCR及Western印迹方法检测MCF-7与LCC2细胞中KLF8 mRNA及蛋白表达差异,免疫组化检测97例Luminal A/B亚型接受TAM治疗乳腺癌中KLF8表达情况并分析其与预后的关系,运用CCK-8试剂盒检测沉默及过表达KLF8后在不同浓度TAM作用下细胞增殖变化。结果:TAM耐药细胞中KLF8表达水平高于TAM敏感细胞,接受TAM治疗Luminal A/B亚型乳腺癌患者中,KLF8高表达者预后差,过表达KLF8后细胞对TAM耐药性增强,而沉默KLF8后细胞对TAM耐药性减弱。结论:KLF8高表达与乳腺癌TAM耐药正相关,在Luminal A/B亚型的乳腺癌中,KLF8高表达TAM治疗效果差,KLF8或可成为TAM疗效判断及逆转耐药的新靶点。

Krüppel样因子4通过支持PPARγ信号通路维持细胞稳态以保护血管平滑肌细胞免受泡沫细胞样表型转化的损害

动脉粥样硬化(AS)被普遍认为是一种血管壁细胞(包括内皮细胞和血管平滑肌细胞)、循环细胞以及固有免疫原性细胞(例如单核细胞/巨噬细胞)等多种细胞综合作用引起的炎症性疾病。其中血管平滑肌细胞(VSMCs)胆固醇超负荷形成的泡沫细胞可能在动脉粥样硬化的进展中发挥重要作用。Krüppel样因子4(KLF4)是一种关键的抗炎转录因子,尤其在心血管疾病方面,已被证实发挥了重要的血管功能保护作用。然而,目前尚不清楚KLF4是否在AS过程胆固醇对VSMCs的损伤中发挥保护作用。该研究旨在探讨KLF4在AS进展过程中VSMCs泡沫细胞样表型转化的作用及其分子机制。小鼠AS造模结果显示,KLF4缺失增加动脉粥样硬化斑块面积(P<0.05),并增加动脉壁脂质蓄积(P<0.05)及血清胆固醇含量(P<0.05),加速AS进展。细胞内油红O染色及胆固醇含量测定研究证实,KLF4缺失促进VSMCs内胆固醇蓄积(P<0.05)。QRT-PCR和Western印迹结果证实,KLF4缺失促进VSMCs胆固醇摄取、合成、促炎因子分泌及巨噬细胞黏附和胆固醇损伤诱导的巨噬细胞标志物的表达(P<0.05),抑制胆固醇流出和氧化相关基因及收缩表型标志物的表达(P<0.05),加速VSMCs源性泡沫细胞形成。KLF4敲除VSMCs中利用腺病毒Ad-GFP-KLF4补救表达KLF4,显著逆转上述改变,并阻断由胆固醇蓄积诱导的TLR4-MyD88-p65通路的激活。随后,siRNA诱导的过氧化物酶体增殖物激活受体γ(PPARγ)的选择性基因消融消除了KLF4的这些作用。总之,我们的研究结果提示,KLF4通过激活PPARγ途径,抑制胆固醇摄取和合成,加速胆固醇流出,同时抑制促炎因子分泌、巨噬细胞黏附和胆固醇损伤诱导的巨噬细胞标志物表达,从而在VSMCs中实现对胆固醇刺激的保护作用。