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miR-625通过负向调控Resistin的表达抑制非小细胞肺癌细胞的恶性生物学行为及其机制

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中国肿瘤生物治疗杂志 2020年第5期27卷 477-486页

作者：张建庆章恒新疆维吾尔自治区人民医院放疗一科新疆乌鲁木齐830001

目的:探究miR-625和Resistin对NSCLC细胞增殖、侵袭、迁移及裸鼠移植瘤生长的影响及其可能的机制。方法:qPCR实验检测80例NSCLC及癌旁组织(标本收集自2018年3月至2019年10月于新疆维吾尔自治区人民医院手术治疗的NSCLC患者)和4种细胞系... 详细信息

目的:探究miR-625和Resistin对NSCLC细胞增殖、侵袭、迁移及裸鼠移植瘤生长的影响及其可能的机制。方法:qPCR实验检测80例NSCLC及癌旁组织(标本收集自2018年3月至2019年10月于新疆维吾尔自治区人民医院手术治疗的NSCLC患者)和4种细胞系中miR-625与Resistin的表达,生物信息学预测两者的靶向关系并用双荧光素酶基因报告实验进行验证;通过脂质体转染技术在NSCLC细胞中过表达或抑制miR-625及Resistin表达,实验分为miR-625 mimic组、miR-625 inhibitor组、si-Resisitin组、miR-625 inhibitor+si-Resisitin组和NC组,利用CCK-8、Transwell及划痕实验检测miR-625与Resistin对NSCLC细胞增殖、侵袭及迁移的影响,Western blotting实验检测两者对NSCLC细胞中EMT相关的PI3K/AKT/Snail通路蛋白表达的影响,裸鼠成瘤实验观察两者对A549细胞移植瘤生长的影响。结果:miR-625在NSCLC组织和4种细胞系中呈低表达、Resistin呈高表达(均PResistin的表达与NSCLC分化程度、临床分期及淋巴结转移相关。Resistin是miR-625的靶基因。在NSCLC细胞系A549和H226的增殖、侵袭、迁移能力及裸鼠移植瘤的生长方面,与Blank组和NC组相比,miR-625 mimic组与si-Resistin组能力均显著降低(均PResistin组显著低于miR-625 inhibitor组(均PResistin组之间无显著差异(均P>0.05);p-AKT、p-PI3K、Snail、Twist1、Vimentin等蛋白表达变化也有相同的趋势(均PResistin表达从而抑制NSCLC细胞的增殖、侵袭和迁移及裸鼠移植瘤生长,其机制可能与PI3K/AKT/Snail信号通路有关。

关键词： miR-625 Resistin 非小细胞肺癌 A549细胞 H226细胞增殖侵袭迁移 PI3K/AKT/Snail

Association between serum Resistin level and cardiovascular events in postmenopausal women with acute coronary syndrome undergoing percutaneous coronary intervention

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Chinese Medical Journal 2013年第6期126卷 1058-1062页

作者： LI Lei HAN Jiang-li MAO Jie-ming GUO Li-jun GAO Wei Department of Cardiology Peking University Third Hospital Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100191 China

Background As an adipocytokine, Resistin has been proposed as a link between inflammation, metabolic disorder and atherosclerosis. The aim of the study is to evaluate whether serum Resistin is associated with acute coronary syndrome （ACS） and major adverse cardiovascular events （MACEs） among postmenopausal women with ACS undergoing percutaneous coronary intervention （PCI）. Methods A total of 106 consecutive postmenopausal women who underwent coronary angiography for evaluation of suspected myocardial ischemia were enrolled. Pre-procedure serum Resistin, inflammatory and metabolic biomarkers were measured. All participants were followed for seven years for MACEs, including cardiovascular death, recurrent nonfatal myocardial infarction, and re-PCl. Results Patients with ACS （n=69） had significantly higher Resistin levels than those without coronary artery disease （CAD）（n=37）（4.61 （1.79-10.80） ng/ml vs. 2.36 （0.85-4.15） ng/ml, P=0.002）. Correlation analysis revealed positive correlations between Resistin levels and inflammatory and metabolic factors （P 〈0.05）. A follow-up of a mean of 83.4 months showed that patients with ACS suffered more MACEs than those without （13.0% vs. 2.7%, P=0.05）. Adjusted for cardiovascular risks, inflammatory and metabolic factors, multiple Logistic regression analysis indicated that an elevated Resistin level was an independent predictor of ACS onset （OR=1.139, 95% CI 1.024-1.268, P=0.017） and of MACEs after PCI （OR=1.099, 95% CI 1.015-1.189, P=-0.019）. To clarify the association between Resistin levels and MACEs, ACS patients were divided into two subgroups on the basis of Resistin levels. Compared with the low Resistin subgroup （≤4.35 ng/ml, n=32）, patients in the high Resistin subgroup （〉4.35 ng/ml, n=37） were more prone to suffer MACEs （21.6% vs. 3.1%, P=0.015）. Kaplan-Meier analysis showed a significantly lower event-free survival rate in ACS patients with high Resistin levels than in the low Resistin subgroup （78.4% vs. 96.9%, Log rank 5.594, P=0.018）. Conclusion An elevated seru

关键词： postmenopausal women Resistin acute coronary syndrome major adverse cardiovascular events

The Relationship Between the Expression of Resistin and Apoptosis Factors in Placenta and the Pathogenesis of Gestational Diabetes Mellitus

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Maternal-Fetal Medicine 2020年第2期2卷 80-83页

作者： Jun Yu Xiao-Ling Su Jing Jia Yu Zeng Jing-Yi Zhang Shao-Shuai Wang Ling Feng Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective::To detect the expression of caspase-3,baculoviral inhibitor of apoptosis repeat containing 5(BIRC-5),vascular endothelial growth factor(VEGF),hypoxia-inducible factor(HIF),and the concentration of Resistin protein in placental of patients with gestational diabetes mellitus(GDM)and normal pregnant women,and to explore its correlation with the pathogenesis of GDM and its significance.Methods::This study includes 30 pregnant women who chose cesarean section at Tongji Hospital of Tongji Medical College during May 2013 to February 2014:15 GDM patients and 15 normal glucose tolerance patients,26-36 years old.The expression of caspase-3,VEGF,HIF,and BIRC-5 in placenta of 15 patients with GDM(GDM group)and 15 normal late pregnancy(control group)was detected by real-time fluorescence quantitative polymerase chain reaction.The concentration of Resistin protein in the placenta was detected by enzyme-linked immunosorbent assay.Results::Compared with the control group,the expression of caspase-3,HIF,VEGF,Resistin in placenta of GDM group increased significantly(PResistin in placenta of GDM patients and normal pregnant women are significantly different,which may be involved in the pathogenesis of GDM disease.

关键词： Diabetes,gestational Placenta Survivin Apoptosis Resistin

Association of higher Resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension

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Chinese Medical Journal 2013年第4期126卷 646-649页

作者： FANG Chang LEI Juan ZHOU Shu-xian ZHANG Yu-ling YUAN Gui-yi WANG Jing-feng Division of Cardiology Department of Internal Medicine and Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Sun Yat-sen Memorial Hospital Sun Yat-sen University Guangzhou Guangdong 510120 China

Background Some studies have shown that serum Resistin levels increase in hypertensive patients. Whether the increase of Resistin is related to inflammatory or vascular endothelial function is still unknown. We investigated the relationship of increased Resistin levels to inflammatory factors and circulating biomarkers of vascular endothelial function in hypertensive patients. Methods One hundred and forty-four nondiabetic patients with new onset, hypertension were recruited. Blood pressure, blood glucose, insulin, Resistin, tumour necrosis factor-a （TNF-a）, interleukin-6 （IL-6）, von Willebrand factor （vWF）, endothelin-1 （ET-1） and nitric oxide （NO） were measured. The homeostasis model assessment, insulin resistance index （HOMA-IR） was calculated. Patients were divided into two groups according to the median level of Resistin. Cytokine levels and indicators of vascular endothelial function were compared. Multiple linear regression was used to determine factors influencing Resistin. Results Serum Resistin ranged from 2.57 ng/ml to 20.18 ng/ml in hypertensive patients. High Resistin group （〉8.36 ng/ml） had higher levels of TNF-a, IL-6, vWF and ET-1 but lower level of NO compared with low Resistin group （P 〈0.01）. Resistin was positively correlated with body mass index, systolic blood pressure, HOMA-IR, low-density lipoprotein cholesterol, TNF-a and ET-1 but negatively correlated with NO （all P 〈0.05）. Multiple linear regression analysis revealed that HOMA-IR, TNF-a, NO and ET-1 are independent predictors of Resistin with standardized regression coefficients of 0.625, 0.368, -0.260 and 0.222, respectively （all P 〈0.01）. Conclusions We conclude that higher Resistin levels are associated with inflammatory activation and endothelial dysfunction, because patients with essential hypertension have increased TNF-a, IL-6, vWF and ET-1 and decreased NO. Moreover, the statistical association of Resistin with TNF-a, NO and ET-1 suggests involvement of Resistin in the progression of hypertension by influencing inflammation and

关键词： hypertension Resistin inflammatory factor endothelial function

Serum Adiponectin and Resistin Levels in Patients with Polycystic Ovarian Syndrome and Their Clinical Implications

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第5期30卷 638-642页

作者：王玉霞谢杏美朱伟杰 Department of Obstetrics and Gynecology the First Clinical College of Ji'nan University Center for Reproductive Immunology Research Ji'nan University

In this study, serum adiponectin and Resistin levels were determined in 46 patients with polycystic ovarian syndrome (PCOS), and their correlation with serum sexual hormones and insulin resistance (IR) were examined.The subjects included 26 obese patients with body mass index (BMI)>25 and 20 non-obese patients with BMI≤25, with 25 obese and 25 non-obese healthy volunteers without PCOS serving as controls.Serum adiponectin and Resistin levels in all subjects were measured, and endocrinal and metabolic indices were also analysed.Our results showed that the serum adiponectin levels in both obese and non-obese PCOS groups were significantly lower than their controls, while the serum Resistin levels in obese and non-obese PCOS group were significantly higher than in their controls (PResistin level significantly higher in the non-obese PCOS group as compared with the obese control group (PResistin level was positively correlated with FIN, HOMA-IR, LH and LH/FSH (PResistin, and adiponectin and Resistin might play important roles in the pathogenesis of IR in PCOS patients.

关键词： polycystic ovary syndrome adiponectin Resistin

电针对胰岛素抵抗肥胖大鼠白色脂肪组织ApN/Leptin/Resistin表达的影响

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电针对胰岛素抵抗肥胖大鼠白色脂肪组织ApN/Leptin/Resistin表达...

作者：胡冰林湖北中医药大学

学位级别：硕士

目的本实验通过高脂饲料喂养Wistar大鼠,从而构建胰岛素抵抗肥胖大鼠模型,采用电针法进行干预,观察电针对白色脂肪组织脂联素（ApN）、瘦素（Leptin）、抵抗素（Resistin）的影响,探讨电针改善胰岛素抵抗肥胖的相关影响和机制。方法将60... 详细信息

目的本实验通过高脂饲料喂养Wistar大鼠,从而构建胰岛素抵抗肥胖大鼠模型,采用电针法进行干预,观察电针对白色脂肪组织脂联素（ApN）、瘦素（Leptin）、抵抗素（Resistin）的影响,探讨电针改善胰岛素抵抗肥胖的相关影响和机制。方法将60只8周龄的Wistar雄性大鼠经给予普通饲料适应性喂养一周后,随机将其分为普通饲料组12只和高脂饲料组48只,其中普通饲料组给予普通饲料喂养,高脂饲料组给予高脂饲料喂养,两组均喂养8周,然后分别从普通饲料组、高脂饲料组随机选取6只、24只Wistar大鼠行高胰岛素-葡萄糖钳夹术,用于评定胰岛素抵抗,计算出上述两组大鼠的Lee’s指数,用于评定肥胖。造模成功后,将高脂饲料组24只胰岛素抵抗肥胖大鼠随机分为模型对照组、电针干预组、假电针干预组、白藜芦醇组,每组各6只;将普通饲料组剩下的6只大鼠取名为正常对照组。其中,正常对照组仅仅给予普通饲料喂养,不予任何其他实验措施;模型对照组仅仅给予高脂饲料喂养,不予任何其他实验措施;电针干预组给予高脂饲料喂养,同时给予电针干预,选取“足三里”“丰隆”“中脘”、“天枢”四穴,针刺后连接韩式电针仪,选取频率为2Hz、强度1mA的连续波,每次治疗10分钟,每天治疗一次,每周治疗7次,总疗程为8周,其中足三里、丰隆、天枢左右交替使用。干预治疗8周后,测量上述5组大鼠的体质量、计算Lee’s指数;从上述各组大鼠行高胰岛素-正葡萄糖钳夹术,测定葡萄糖输注率（GIR值）;并且进行腹主动脉取血,用ELISA试剂盒检测血清FFA、TC、TG水平含量;然后取下白色脂肪组织,用免疫印迹法（Western Blotting,WB）检测ApN、Leptin、Resistin蛋白表达的水平;最后通过SPSS软件对整个数据进行统计学分析和处理。结果1.高脂喂养8周后对Wistar大鼠体重、Lee’s指数、GIR值的影响经过8周喂养后,高脂饲料组大鼠体重、Lee’s指数显著高于普通饲料组（P＜0.01）;高脂饲料组大鼠GIR值显著低于普通饲料组（P＜0.01）。2.电针干预8周后对大鼠体重、Lee’s指数、GIR值的影响各组大鼠体重、Lee’s指数:模型组的体重、Lee’s指数明显高于正常对照组（P＜0.01）;模型组的体重、Lee’s指数明显高于电针干预组、白藜芦醇组,具有统计学意义（P＜0.01）;假电针干预组大鼠的体重、Lee’s指数呈下降趋势,但与模型对照组比较,经统计学处理,模型对照组和假电针干预组两者之间无统计学意义（P＞0.05）;电针干预组体重明显低于假电针干预组,具有统计学意义（P＜0.05）;电针干预组虽然体重低于白藜芦醇组,但两者之间无统计学意义（P＞0.05）。各组大鼠GIR值比较:模型对照组明显低于正常对照组（P＜0.05）;模型对照组明显低于电针干预组、白藜芦醇组（P＜0.05）;电针干预组明显高于假电针干预组（P＜0.05）;假电针干预组与模型对照组两者之间无统计学意义（P＞0.05）;电针干预组虽然稍高于白藜芦醇组,但两者之间亦无统计学意义（P＞0.05）。3.电针对胰岛素抵抗肥胖大鼠血清FFA、TC、TG水平含量的影响各组大鼠血清TC、TG、FFA水平比较:模型对照组明显高于正常对照组（P＜0.05）;电针干预组、白藜芦醇组明显低于模型对照组,具有统计学意义（P＜0.05）;电针组的血清TC、TG、FFA水平,虽然较低于白藜芦醇组,但两组之间比较,无统计学意义（P＞0.05）;假电针干预组与模型组相比较,两者之间无统计学意义（P＞0.05）;电针干预组低于假电针干预组（P＜0.05）。4.电针对胰岛素抵抗肥胖大鼠白色脂肪组织ApN、Leptin、Resistin蛋白表达水平的影响与正常对照组相比,模型对照组APN蛋白表达水平较高,两组比较无统计学意义（P＞0.05）;模型对照组APN蛋白表达水平明显低于电针干预组、假电针干预组及白藜芦醇组,具有统计学意义（P＜0.05）;电针干预组APN蛋白表达水平高于白藜芦醇组,两组比较有统计学意义（P＜0.05）;电针干预组APN蛋白表达水平高于假电针干预组,两组比较无统计学意义（P＞0.05）。与正常对照组相比,模型对照组Leptin蛋白表达水平明显升高,具有统计学意义（P＜0.05）;模型对照组Leptin蛋白表达水平明显高于电针干预组、假电针干预组及白藜芦醇组,具有统计学意义（P＜0.05）;电针干预组Leptin蛋白表达水平低于白藜芦醇组,两组比较有统计学意义（P＜0.05）;电针干预组Leptin蛋白表达水平低于假电针干预组,两组比较有统计学意义（P＜0.05）。与正常对照组相比,模型对照组Resistin蛋白表达水平有升高,但无统计学意义（P＞0.05）;模型对照组Resistin蛋白表达水平明显高于电针干预组、假电针干预组及白藜芦醇组,具有统计学意义（P＜0.05）;电针干预组Resisti

关键词：电针胰岛素抵抗肥胖 ApN Leptin Resistin

Resistin基因对胰岛β细胞RINm5F增殖的影响

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中国当代儿科杂志 2010年第1期12卷 43-46页

作者：刘峰邱洁张春梅季晨博郭锡熔南京医科大学附属南京儿童医院呼吸科江苏南京210029 南京医科大学儿科研究所江苏南京210029

目的Resistin被认为是联系肥胖与2型糖尿病的脂肪因子。本研究旨在探讨Resistin基因过表达对胰岛β细胞株RINm5F增殖的影响。方法体外培养RINm5F大鼠胰岛β细胞,通过pcDNA3.1-Resistin真核表达质粒转染RINm5F细胞,筛选稳定表达株。采用... 详细信息

目的Resistin被认为是联系肥胖与2型糖尿病的脂肪因子。本研究旨在探讨Resistin基因过表达对胰岛β细胞株RINm5F增殖的影响。方法体外培养RINm5F大鼠胰岛β细胞,通过pcDNA3.1-Resistin真核表达质粒转染RINm5F细胞,筛选稳定表达株。采用四甲基偶氮唑盐(MTT)法检测细胞增殖,采用RT-PCR法验证Resistin mRNA水平及检测SOCS-3的mRNA水平,Western blot法检测Akt的总蛋白和磷酸化水平。结果过表达Resistin的RINm5F细胞增殖速度显著低于正常对照组(PResistin的RINm5F细胞中Akt磷酸化水平为正常对照组的0.6倍(PResistin基因过表达减缓了胰岛β细胞RINm5F的增殖,其机制可能与上调了SOCS-3从而导致Akt下调有关。

关键词： Resistin 增殖胰岛β细胞

Prolonged exposure to Resistin inhibits glucose uptake in rat skeletal muscles

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Acta Pharmacologica Sinica 2007年第3期28卷 410-416页

作者： Hong-qi FAN~(2,3) Nan GU~(2,3) Feng LIU~2 Li EEI~2 Xiao-qin PAN~2 Mei GUO~2 Rong-hua CHEN~(2,4) Xi-rong GUO~(2,3,4)2 Department of Pediatrics,Nanjing Maternal and Child Health Hospital of Nanjing Medical University,Nanjing 210004,China 3 Institute of Pediatrics Medicine,Nanjing Medical University,Nanjing 210029,China Department of Pediatrics Nanjing Maternal and Child Health Hospital of Nanjing Medical University Nanjing China Institute of Pediatrics Medicine Nanjing Medical University Nanjing China

Aim:To assess the effects and mechanisms of the action of Resistin on basal andinsulin-stimulated glucose uptake in rat skeletal muscle cells.Methods:Rat myo-blasts(L6)were cultured and differentiated into myotubes followed by stimula-tion with single commercial Resistin(130 ng/mL,0-24 h)or cultured supernatantfrom 293-T cells transfected with Resistin-expressing vectors(130 ng/mL,0-24 h).Liquid scintillation counting was used to quantitate[~3H]2-deoxyglucose uptake.The translocation of insulin-sensitive glucose transporters GLUT4 and GLUT1,synaptosomal-associated protein 23(SNAP23)and GLUT protein content,as wellas the tyrosine phosphorylation status and protein content of insulin receptorsubstrate(IRS)-1,were assessed by Western blotting.Results:Treatment of L6myotubes with single Resistin or cultured supernatant containing recombinantResistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impairedinsulin-stimulated GLUT4 translocation.While SNAP23 protein content wasdecreased,no effects were noted in GLUT4 or GLUT1 protein content.Resistinalso diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels withoutaffecting its protein content.The effects of recombinant Resistin from 293-T cellstransfected with Resistin-expressing vectors were greater than that of single Resistintreatment.Conclusion:Resistin regulated IRS-1 function and decreased GLUT4translocation and glucose uptake in response to insulin.The downregulatedexpression of SNAP23 may have been partly attributed to the decrease of glucoseuptake by Resistin treatment.These observations highlight the potential role ofResistin in the pathophysiology of type 2 diabetes related to obesity.

关键词： Resistin insulin glucose uptake obesity diabetes

小鼠Resistin基因慢病毒表达载体构建及在KMB17细胞中的表达

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生物技术 2016年第2期26卷 119-125,135页

作者：陈瑜赵远岳俊李鸿钧和占龙马开利马进吴正存唐东红鲁帅尧中国医学科学院北京协和医学院医学生物学研究所中国医学科学院医学灵长类动物研究中心云南省重大传染病疫苗研发重点实验室云南昆明650118

[目的]构建携带小鼠Resistin基因的慢病毒表达载体,并高效转导靶细胞。[方法]从小鼠脂肪组织提取总RNA,经PCR扩增、酶切、连接、转化后构建重组质粒;通过293T细胞包装为重组慢病毒颗粒,然后感染KMB17细胞,检测小鼠Resistin基因在靶细胞... 详细信息

[目的]构建携带小鼠Resistin基因的慢病毒表达载体,并高效转导靶细胞。[方法]从小鼠脂肪组织提取总RNA,经PCR扩增、酶切、连接、转化后构建重组质粒;通过293T细胞包装为重组慢病毒颗粒,然后感染KMB17细胞,检测小鼠Resistin基因在靶细胞中的表达。[结果]PCR扩增到预期的342 bp大小的Resistin基因目的片段;构建的重组质粒经酶切得到了342 bp大小的目的片段,测序鉴定为小鼠Resistin基因序列;重组慢病毒包装可观察到很强的绿色荧光,说明具有较高的质粒转染效率;重组慢病毒感染KMB17后可检测到小鼠Resistin基因转录水平和蛋白水平的表达,证明Resistin基因得到有效转导并可在靶细胞中高水平表达。[结论]成功构建了携带小鼠Resistin基因的慢病毒表达载体并可在KMB17靶细胞中获得高效表达。

关键词： Resistin 慢病毒载体靶细胞表达小鼠