成纤维细胞生长因子-21与糖尿病

成纤维细胞生长因子-21(FGF-21)是成纤维细胞家族成员之一,其受体可能为FGFR-1和FGFR-2,与受体的结合可能需要βKlotho,过氧化物酶体增殖物活化受体(PPAR)α对FGF-21的分泌起重要的调节作用.FGF-21可通过蛋白激酶B(Akt)信号转导途径抵抗细胞因子和糖脂毒性诱导的β细胞凋亡,通过非胰岛素信号依赖通路降低血糖,并且能改善脂代谢、刺激胰岛素分泌,且与PPARγ信号转导途径存在相互协同作用,显示出潜在的糖尿病治疗作用.     

成纤维细胞生长因子与血管成形术后再狭窄

成纤维细胞生长因子的酸性分子和碱性分子均有促进血管平滑肌细胞分裂，增生的作用，对血管内皮细胞亦有丝裂源和趋化作用，并可在体内诱导毛细血管形成；它们在血管成形术后再狭窄过程中起着非常重要的作用。亦有报道极低剂量的酸性分子有抑制平滑肌细胞增生的作用，这样可能在防止血管成形术后再狭窄中发挥作用。     

成纤维细胞生长因子21对载脂蛋白E基因敲除小鼠动脉粥样硬化病变中内质网应激诱导的凋亡的影响

目的　探讨成纤维细胞生长因子21（FGF-21）对载脂蛋白E基因敲除（ApoE^-/-）小鼠主动脉中内质网应激诱导的凋亡的影响。方法　将24只ApoE^-/-小鼠随机分为动脉粥样硬化模型组（简称模型组）和FGF-21组（n12）,另选12只C57BL/6J小鼠作为正常对照组,三组小鼠都给予高胆固醇饮食4周,同时FGF-21组皮下给予FGF-21［0.1　mg　/（kg·d）］4周,而模型组和正常对照组给予等量生理盐水。4周后处死小鼠进行主动脉病理学检测,观察斑块面积,采用放射免疫法检测血浆中FGF-21的水平,采用免疫组织化学染色和Western　Blot检测主动脉成纤维细胞生长因子受体1（FGFR-1）的表达水平,采用Tunel染色检测主动脉斑块中的细胞凋亡水平,采用Western　Blot检测主动脉中剪切后Caspase-12和C/EBP　同源蛋白（CHOP）的表达水平。结果　与正常对照组比较,模型组血浆中的FGF-21水平及主动脉中FGFR1蛋白表达显著升高　（P<0.05）,模型组主动脉根部斑块面积、细胞凋亡数量、剪切后Caspase-12及CHOP蛋白的表达水平增加（P<0.05）;与模型组比较,FGF-21组主动脉根部斑块面积、细胞凋亡数量、剪切后Caspase-12及CHOP蛋白的表达水平减少（P<0.05）。结论　FGF-21可能通过抑制剪切后Caspase-12及CHOP相关促凋亡蛋白表达,抑制ApoE^-/-小鼠主动脉斑块病变中细胞的凋亡及斑块进展。     

碱性成纤维细胞生长因子与低氧性肺血管重构

慢性低氧能导致肺动脉高压的形成，其病理基础为肺小动脉结构的重构。肺血管构型重构（pulmonary vascular structure remodeling，PVSR）表现为肺动脉中膜SMC增生、肥大，外膜纤维母细胞增殖，细胞外基质增多，并导致管壁增厚和管腔狭窄。现有的研究表明其发生可能涉及到多种细胞因子及生长因子的相互作用。碱性成纤维细胞生长因子（basic Fibroblast Growth Factor，bFGF）是肝素结合生长因子家族成员之一，在体内分布广泛。它既是生长因子，也是丝裂原。正常情况下不发挥作用，在缺氧时由于内皮受损，细胞完整性破坏，使储存的bFGF释放，导致血管内皮细胞和SMC增生、肥大和迁移。本文主要就bFGF参与低氧性肺血管重构的机制作一综述。     

初诊2型糖尿病患者血浆成纤维细胞生长因子21水平与相关因素

目的 本研究探讨2型糖尿病（T2DM）患者血浆成纤维细胞生长因子21（FGF-21）水平变化及其与体质指数（BMI）、血糖、血浆胰岛素水平等因素的关系.方法 选取2013年1月至7月于首都医科大学附属北京朝阳医院内分泌科就诊患者180例为研究对象,分为新诊断T2DM组（DM组,136例）,糖耐量受损组（IGR组,44例）,另选取同期体检健康志愿者52名为对照组（NDM组）,应用ELISA方法测定了上述人群的血浆FGF-21水平,并分析血浆FGF21水平与BMI、血糖、血脂、血浆胰岛素、胰岛素抵抗指数（HOMA-IR）、胰岛素敏感指数（HOMA-ISI）等的关系.组间比较采用独立样本t检验进行统计学分析.采用Pearson法进行相关性分析,相关因素分析采用多元线性回归分析法.结果 初诊T2DM患者血浆FGF21水平明显高于健康对照组（319.2±2.5比223.1± 1.4,t=2.804,P＜0.05）.初诊T2DM患者、健康对照组血浆FGF-21水平均与TG水平呈正相关（r=0.26、0.38,均P＜0.05）;在IGR组,血浆FGF-21水平与BMI呈正相关（r=0.33,P＜0.05）.多元回归分析表明HOMA-ISI是影响T2DM患者血浆FGF21水平的独立相关因素.结论 初发2型糖尿病患者血浆FGF21水平的改变与甘油三酯水平及胰岛素抵抗有关.     

成纤维细胞生长因子促血管形成作用的研究进展

缓慢进展的冠状动脉闭塞常引起缺血心肌侧枝循环的形成，目前认为这些侧枝循环的形成与成纤维细胞生长因子的作用密切相关，其潜在的临床意义已得到心血管界的重视，这些研究为药物血管搭桥的设想提供了新思路     

成纤维细胞生长因子与卒中后血管发生

增加缺血半暗带脑血流有利于促进神经功能恢复.成纤维细胞生长因子与卒中后血管发生密切相关,可使缺血半暗带脑血流得到改善,从而促进神经功能恢复.其应用将成为治疗缺血性卒中的一种新方法.     

成纤维细胞生长因子21与胰岛素抵抗

研究表明,成纤维细胞生长因子21(FGF21)可以改善胰岛素抵抗、增加胰岛素敏感性.其通过保护胰岛β细胞、与胰岛素协同、增强线粒体氧化、促进脂联素分泌等发挥作用.脑室内给予FGF21也可改善胰岛素敏感性.FGF21为治疗2型糖尿病、肥胖等疾病带来了新方向.     

The serum fibroblast growth factor 21 is correlated with retinopathy in patients with type 2 diabetes mellitus

Aimsdespite advances in blood glucose control, the incidence of sight loss has not decreased in patients with diabetes. Several growth factors have been suggested as factors associated with diabetic retinopathy pathogenesis. In the current cross-sectional study, we examined the relationship between FGF21 and retinopathy as a microvascular complication of diabetes.MethodsAdult patients with type 2 diabetes mellitus (T2DM); were recruited and evaluated for retinopathy. Different clinical and biochemical factors, such as FGF21 were assessed and compared between groups.Results91 T2DM patients with retinopathy, 93 T2DM patients without retinopathy, and 86 healthy control subjects were recruited. FGF21 was significantly different between the three groups (P<0.001). In the multivariate logistic regression model obesity, cholesterol, HbA1c, and FGF21 were associated with diabetic retinopathy. ROC curve analysis was used for establishing a cut-off FGF21 concentration to predict diabetic retinopathy. The area under the curve in this model was 0.992. The best cut-off point for predicting retinopathy based on FGF21 was greater than 312 pg/ml, with a sensitivity of 97.80% and specificity of 96.77%.ConclusionFGF21 was associated with diabetic retinopathy and can be suggested as a surrogate diagnostic marker in the diagnosis of this state.     

成纤维细胞生长因子21基因在心脏中表达的研究

目的:探讨成纤维细胞生长因子21(Fibroblast growth factor 21,FGF21)基因是否在心脏中表达及其表达水平,为进一步研究FGF21与动脉粥样硬化发生发展的关系提供理论基础。方法:对培养的乳鼠心肌细胞、大鼠心脏微血管内皮细胞进行RealTime-PCR定量检测,并与FGF21的主要来源肝脏进行比较,测定FGF21基因在心肌细胞与内皮细胞中的表达水平。结果:RealTime-PCR结果显示FGF21基因在心肌细胞与内皮细胞中均有表达,且ΔCt值肝脏显著低于心肌细胞与内皮细胞[(5.50592±0.18630)vs(11.26081±0.25024)vs(15.99978±0.17076),P<0.05]。结论:ΔCt值与样品中FGF21基因的表达成反比,即肝脏组织表达FGF21基因的水平高于心肌细胞与内皮细胞。此外本研究发现,心肌细胞与内皮细胞中均有FGF21基因表达,可能对心肌损伤起一定作用。     

成纤维细胞生长因子21心肌保护作用的研究进展

成纤维细胞生长因子21(FGF21)主要参与糖脂代谢的调节,与肥胖、糖尿病、代谢综合征和非酒精性脂肪肝等多种疾病或病理过程密切相关。目前研究表明,FGF21可以拮抗心肌缺血和缺血再灌注损伤,发挥明显的心肌保护作用,其作用机制可能与抗心肌细胞凋亡、抗炎、抗氧化应激、调节心肌细胞能量代谢和线粒体功能等有关。本综述简要概括FGF21心肌保护作用及其机制的研究进展。     

高脂喂养apoE~(-/-)小鼠组织成纤维细胞生长因子21及其受体的改变

目的 探讨在环境和遗传因素共同诱导的胰岛素抵抗状态下组织成纤维细胞生长因子21(FGF-21)及其受体(FGFR)的变化.方法 雄性apoE~(-/-)小鼠,随机分为普通喂养组(NF组,n=20)和高脂喂养组(HF组,n=20),喂养16周.以3-[~3H]-葡萄糖为示踪剂的扩展胰岛素钳夹技术评价小鼠胰岛素敏感性和糖代谢变化.用实时荧光定量PCR法检测肝脏和脂肪组织FGF-21、FGFR1、FGFR2、FGFR3和FGFR4以及β-klotho mRNA表达,用Western印迹法测定血浆和组织FGF-21蛋白水平.结果 HF组小鼠空腹血糖、血浆胰岛素、甘油三酯、游离脂肪酸和胆固醇水平明显升高(均P<0.01).在钳夹稳态时,HF组血浆胰岛素水平明显高于NF组(P<0.01),HF组葡萄糖输注率(GIR)明显低于NF组(P<0.01).在钳夹结束时,HF组葡萄糖清除率(G_(Rd))明显低于NF组(P<0.01).钳夹稳态期,NF和HF组肝糖输出率(HGP)分别被抑制约70%和51%(均P<0.01).HF组肝和脂肪组织FGF-21和β-klotho mRNA水平均明显高于NF组(均P<0.01).HF组肝和脂肪组织FGFR1和FGFR3 mRNA的表达明显较NF组显著增高(P<0.01和P<0.05).FGFR4 mRNA水平在HF组肝组织中的表达明显高于NF组(P<0.05).HF组血浆FGF-21蛋白水平明显高于NF组(P<0.01),肝和脂肪组织FGF-21蛋白水平也显著升高(均P<0.05).结论 高脂喂养apoE~(-/-)小鼠FGF-21、β-Klotho及FGFR1和FGFR3水平显著升高,它们可能是FGF-21调节糖脂代谢的主要作用靶点.     

Serum fibroblast growth factor 21 concentrations in type 2 diabetic retinopathy patients

Aims/purposeFibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition.MethodsIn a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis.ResultsSerum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P = 361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR = 13.772, 95% CI = 3.062–61.948, P = 001).ConclusionsSerum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5 pg/mL).     

非酒精性脂肪性肝炎患者血清成纤维细胞生长因子-21和脂联素水平变化及其临床意义探讨

目的 探讨非酒精性脂肪性肝炎(NASH)患者血清成纤维细胞生长因子-21(FGF21)、脂联素(APN)和胰岛素抵抗水平变化及其临床意义。方法 2 018年7月～2019年8月我院就诊的41例NASH患者和41例同期健康人群,检测空腹血糖(FBG)和空腹胰岛素(FINS),计算稳态模型胰岛素抵抗(HOMA-IR)指数,采用ELISA法检测血清FGF21水平,采用放射免疫法检测血清APN水平。结果 NASH患者FBG水平为(8.7±1.6)mmol/L,显著高于健康人【(5.6±0.5)mmol/L,P<0.05】,FINS水平为(30.9±9.8)μIU/mL,显著高于健康人【(12.5±3.6)μIU/mL,P<0.05】,HOMA-IR水平为(1.9±1.1),显著低于健康人【(3.8±2.5),P<0.05】;NASH血清FGF21水平为(279.7±106.4)pg/mL,显著高于健康人【(141.2±62.5) pg/mL,P<0.05】,血清APN水平为(2.9±0.8)μg/mL,显著低于健康人【(4.1±1.0)μg/mL,P<0.05】;10例重度组患者血清FGF21水平为(285.7±116.4)pg/mL,显著高于16例中度组和15例轻度组【分别为(174.5±75.3)pg/mL和(150.7±65.5)pg/mL,P<0.05】,血清APN水平为(2.1±0.5)μg/mL,显著低于中度组和轻度组【分别为(2.6±0.9)μg/mL和(3.0±1.1)μg/mL,P<0.05】,FBG水平为(9.9±2.6)pg/mL,显著高于中度组和轻度组【分别为(7.5±2.1)pg/mL和(6.6±1.5)pg/mL,P<0.05】,FINS水平为(35.9±8.8)pg/mL,显著高于中度组和轻度组【(27.1±4.0)pg/mL和(15.5±3.6)pg/mL,P<0.05】,HOMA-IR水平为(1.5±1.0),显著低于中度组和轻度组【分别为(1.7±1.2)和(2.1±1.0),P<0.05】;17例存在高血压糖尿病或高脂血症的NASH患者血清FGF21水平为(315.7±99.2)pg/mL,显著高于24例无合并症组【(254.2±91.1)pg/mL, P<0.05】,血清APN水平为(2.6±0.7)μg/mL,显著低于无合并症组【(3.1±0.8)μg/mL,P<0.05】。结论 合并有高血压、糖尿病和高脂血症的NASH患者血清FGF21水平升高,而血清APN和胰岛素抵抗指标降低,检测NASH患者血清FGF21、APN和胰岛素抵抗水平,有助于评估患者病情。     

Structural and biochemical properties of fibroblast growth factor 23

Fibroblast growth factor (FGF) 23 shares a fundamentally common structure with the members of the FGF family and has a unique sequence extension at the C-terminus. The molecular behavior of FGF23 as a systemic factor can be justified by the altered conformation of the beta-trefoil structure similar to that suspected in FGF19. On the other hand, the biological activity of FGF23 is quite distinct from those of other FGFs and requires the C-terminal unique extended structure. Two types of enzyme-linked immunosorbent assays (ELISA) have been developed to detect the intact mature form of FGF23 and its C-terminal portion. The former ELISA method enables the detection of rodent FGF23 and human FGF23. Studies on experimental animal models and laboratory examinations of physiologic and disordered conditions using these assays are contributing toward elucidating the physiology and pathophysiology of FGF23.