Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

Serum fibroblast growth factor 21: Lack of association with gestational diabetes and pregnancy outcomes

BACKGROUND The prevalence of gestational diabetes mellitus(GDM)has been increasing worldwide and is associated with multiple adverse pregnancy outcomes.Despite standard screening,some cases remain undiagnosed.Fibroblast growth factor 21(FGF21)plays a role in modulating glucose metabolism.There is an ongoing controversy regarding the relevance of FGF21 to GDM.AIM To evaluate the association between early second trimester serum FGF21 levels and gestational diabetes,and its predictive potential for outcomes.METHODS This cross-sectional observational study was conducted at a tertiary medical center,Chiang Mai University,Thailand.It included 28 pregnant women diag-nosed with GDM and 81 pregnant women with normal glucose status.Blood samples were collected according to the study schedule,and pregnancy outcomes were recorded meticulously.Descriptive analysis was employed to evaluate the data.RESULTS Most participants in our study had no risk factors for GDM(body mass index<24 kg/m2,no first-degree relatives with diabetes,no history of GDM),normal baseline glucose status(fasting glucose<110 mg/dL),and no insulin resistance(homeostatic model assessment of insulin resistance<2).There was a trend of increased FGF21 levels in the insulin-treated GDM group compared with dietary-treated GDM and non-GDM(73.58 pg/mL vs 62.94 pg/mL vs 63.59 pg/mL,respectively,P=0.73).However,no significant association was found between FGF21 concen-trations and pregnancy outcomes based on quintiles of FGF21 levels.CONCLUSION FGF21 was not associated with GDM or pregnancy outcomes;however,due to the small sample size,larger clinical trials with a diverse population are suggested to confirm these results.

Fibroblast growth factor 21 in dairy cows:current knowledge and potential relevance

Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress conditions.Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation.It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation.This finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or humans.However,the role of FGF21 in dairy cows has been less investigated so far.Following a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows.The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows.In the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed.In the third part,findings of exogenous FGF21 application on metabolism in dairy cows are reported.Finally,the potential relevance of FGF21 in dairy cows is discussed.It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows.However,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.

Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression

AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. METHODS： Hale rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group （R）, aFGF treatment group （A）, intestinal ischemia group （I）, and sham-operated control group （C）. In group I, the animals were killed after 45 min of superior mesenteric artery （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA occlusion and were treated with normal saline （0.15 mL） and aFGF （20 μg/kg, 0.15 mL）, then sustained at various times for up to 48 h after reperfusion. In group C, SHA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique （TUNEL）. Intestinal tissue samples were taken not only for RT- PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS： In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were （41.17±3.49）%, （42.83±5.23）%, and （53.33±6.92）% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points （50.67±6.95）%, （54.17±7.86）%, and （64.33±6.47）%, respectively, （P〈0.05））. The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group （P〈0.05） at 2-12 h after reperfusion, while the mRNA levels of P53 and P21VVAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion （P〈0.05）. CONCLUSION： P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

BACKGROUND The importance of early diagnosis of alcoholic liver disease underscores the need to seek better and especially non-invasive diagnostic procedures.Leukocyte cellderived chemotaxin-2(LECT2)has been widely studied to determine its usefulness in monitoring the course of non-alcoholic fatty liver disease but not for alcoholic liver cirrhosis(ALC).AIM To determine the concentration of LECT2 in the blood serum of patients in relation to progressive stages of ALC,its relation to fibroblast growth factor 1(FGF-1)and FGF-21,and to examine the possible wider use of LECT2 in diagnosing ALC.METHODS A retrospective case-control study was conducted with 69 ALC cases and 17 controls with no ALC.Subjects were recruited from the region of Lublin(eastern Poland).Liver cirrhosis was diagnosed based on clinical features,history of heavy alcohol consumption,laboratory tests,and abdominal ultrasonography.The degree of ALC was evaluated according to Pugh-Child criteria(the Pugh-Child score).Blood was drawn and,after centrifugation,serum was collected for analysis.LECT2,FGF-1,and FGF-21 were determined using enzyme-linked immunosorbent assay kits.RESULTS The LECT2 Levels in the control group were 18.99±5.36 ng/mL.In the study groups,they declined with the progression of cirrhosis to 11.06±6.47 ng/mL in one group and to 8.06±5.74 ng/mL in the other(P<0.0001).Multiple comparison tests confirmed the statistically significant differences in LECT2 Levels between the control group and both test groups(P=0.006 and P<0.0001).FGF-21 Levels were 44.27±64.19 pg/mL in the first test group,45.4±51.69 pg/mL in the second(P=0.008),and 13.52±7.51 pg/mL in the control group.The difference between the control group and the second test group was statistically significant(P=0.007).CONCLUSION We suggest that LECT2 may be a non-invasive diagnostic factor for alcoholinduced liver cirrhosis.The usefulness of LECT2 for non-invasive monitoring of alcohol-induced liver cirrhosis was indirectly confirmed by the multiple regression model developed on the basis of our statistical analysis.

Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice

BACKGROUND Fibroblast growth factor 21(FGF21),primarily secreted by the pancreas,liver,and adipose tissues,plays a pivotal role in regulating glucose and lipid metabolism.Acute pancreatitis(AP)is a common inflammatory disease with specific clinical manifestations.Many patients with diabetes present with concurrent inflammatory symptoms.Diabetes exacerbates intestinal permeability and intestinal inflammation,thus leading to the progression to AP.Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice.AIM To investigate the potential protective role of FGF21 against AP in diabetic mice.METHODS In the present study,a mouse model of AP was established in diabetic(db)/db diabetic mice through ceruletide injections.Thereafter,the protective effects of recombinant FGF21 protein against AP were evaluated,with an emphasis on examining serum amylase(AMS)levels and pancreatic and intestinal inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-alpha(TNF-),and intestinal IL-1β].Additionally,the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP.An antibiotic(Abx)cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, thePhylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformaticssoftware package, was used to predict different pathways between the groups and to explore the potentialmechanisms by which the gut microbiota influenced the protective effect of FGF21.RESULTSThe results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01)and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ±0.051, P < 0.01), and IL-1β (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notablesigns of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation inthe small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantlyaltered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment withan Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ±0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinaltissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P <0.001). These findings underscored the superior protective effects of the combination therapy involving an Abxcocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota compositionacross different groups was further characterized, and a differential expression analysis of gene functions wasundertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confertherapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathwayof n-acetylceramide degradation in the gut microbiota.CONCLUSION This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing bloodglucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effectsof FGF21 are augmented when combined with the Abx cocktail.

Expression of Fibroblast Growth Factor 21 in Escherichia coli Induced by Lactose

[ Objective] This study aimed to investigate the expression of recombinant protein of fibroblast growth factor 21 （ FGF21 ） in Escherichia coli induced by lactose and explore the possibility of engineering production. [ Method ] The effects of lactose concentration, induction duration, induction starting time, and induc- tion temperature on expression of the recombinant product were compared, and the optimal condition for lactose induction was determined with IPTG induction as a control. [ Result] As an induction agent, lactose plays an ideal rele in the production of recombinant FGF21. In addition, the expression level of lactose induction product is consistent with that of IPTG induction product. Induction in a 250 rrd flask containing 50 ml of medium at A600 0.8 - 1.0 using 0.5 g/L lactose at 35 ℃ for 6 h are the optimal condition. [ Conclusion] Lactose can induce the expression of FGF21 gene and achieve ideal results. This study provides experimental basis and reference for the industrial production of FGF21.

血清GDF-15、FGF-21水平对脓毒症患者病情评估及预后预测的临床价值

目的探讨血清生长分化因子15(GDF-15)、成纤维化生长因子21(FGF-21)水平对脓毒症患者病情评估及其对预后的预测价值。方法回顾性将2020年1月至2023年6月承德医学院附属医院ICU收治的脓毒症患者102例作为研究对象。按Sepsis-3脓毒症诊断标准,按病情不同将患者分为脓毒症组(n=46)与脓毒症休克组(n=56);并按28 d预后不同将患者分为存活组(n=75)与死亡组(n=27)。收集患者常规临床资料,包括性别、年龄、白细胞(WBC)计数、D-二聚体、淋巴细胞(LY)计数、入院24 h的急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分。比较不同组别临床资料及血清GDF-15、FGF-21水平差异,分析患者GDF-15、FGF-21与APACHEⅡ评分的关系,并使用受试者操作特征(ROC)曲线评价GDF-15、FGF-21对患者28 d死亡的预测价值。结果脓毒症组与脓毒症休克组的性别构成比、年龄、LY等比较,差异均无统计学意义(P>0.05);脓毒性休克组WBC、D-二聚体、APACHEⅡ评分、GDF-15、FGF-21水平均高于脓毒症组,且28 d病死率高于脓毒症组,差异均有统计学意义(P<0.05)。死亡组与存活组的性别构成比、年龄、LY比较,差异均无统计学意义(P>0.05);死亡组WBC、D-二聚体、APACHEⅡ评分、血清GDF-15、FGF-21水平均高于存活组,差异均有统计学意义(P<0.05)。经Pearson相关分析得出,脓毒症患者血清GDF-15、FGF-21水平与APACHEⅡ评分均呈正相关(r=0.378、0.394,P<0.001)。Logistic回归分析得出,血清GDF-15(OR=1.169,95%CI:1.041~1.312)、FGF-21水平(OR=1.406,95%CI:1.129~1.752)和APACHEⅡ评分(OR=1.346,95%CI:1.095~1.653)均是脓毒症患者28 d死亡的危险因素(P<0.05)。ROC曲线分析得出,血清GDF-15、FGF-21预测脓毒症患者28 d死亡的曲线下面积(AUC)分别为0.888、0.820,与APACHEⅡ评分(AUC为0.867)相比差异均无统计学意义(P>0.05)。结论血清GDF-15、FGF-21水平增高与脓毒症患者病情较重相关,且对患者预后有一定预测能力。

非酒精性脂肪性肝病合并2型糖尿病患者血清FGF-21和microRNA-21水平的变化及其临床意义

目的探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病患者血清成纤维细胞生长因子-21(FGF-21)和microRNA-21(miR-21)水平变化及其临床意义。方法选取2020年1月—2024年1月聊城市第二人民医院收治的106例NAFLD合并2型糖尿病患者,根据患者NAFLD纤维化程度,将进展性纤维化患者作为观察组(27例),非进展性肝纤维化患者作为对照组(79例)。收集患者的临床资料,对比两组患者的脂质代谢、糖代谢、肝脏硬度,并检测患者血清FGF21水平和miR-21相对表达量。结果观察组甘油三酯(TG)和肝脏弹性硬度值(LSM)均高于对照组(P<0.05),高密度脂蛋白(HDL-C)低于对照组(P<0.05)。观察组糖化血红蛋白(HbA1c)和胰岛素抵抗指数(HOMA-IR)均高于对照组(P<0.05),FGF-21水平和miR-21相对均表达量低于对照组(P<0.05)。多因素一般Logistic回归分析,结果显示:TG水平[OR=3.710(95%CI:1.288,10.688)]、LSM[OR=1.657(95%CI:1.188,2.311)]、HbA1c水平[OR=1.806(95%CI:1.184,2.754)]、HOMA⁃IR水平[OR=8.423(95%CI:2.860,24.804)]均是进展性肝纤维化的危险因素(P<0.05);HDL-C水平[OR=0.002(95%CI:0.000,0.042]、FGF-21水平[OR=0.229(95%CI:0.056,0.940)]和miR⁃21相对表达量[OR=0.020(95%CI:0.000,0.785)]均是进展性肝纤维化的保护因素(P<0.05)。受试者工作特征曲线结果显示,LSM、FGF-21、miR-21联合预测进展性肝纤维化的曲线下面积为0.925(95%CI:0.865,0.988),敏感性为92.6%(95%CI:0.757,0.991),特异性为83.5%(95%CI:0.735,0.914)。结论NAFLD合并2型糖尿病患者血清FGF-21水平和miR-21相对表达量对病情进展有重要意义,是预测进展性肝纤维化的重要指标。

血清FGF-21、Gal-3联合对肥胖型多囊卵巢综合征患者体外受精-胚胎移植治疗后妊娠结局的预测价值

目的探讨血清成纤维细胞生长因子21(FGF-21)、半乳糖凝集素-3(Gal-3)联合对肥胖型多囊卵巢综合征(PCOS)患者体外受精-胚胎移植(IVF-ET)治疗后妊娠结局的预测价值。方法选取2019年2月至2023年2月在南阳市中心医院确诊的98例肥胖型PCOS患者作为研究对象,根据IVF-ET治疗后的妊娠结局分为成功组(n=48)和失败组(n=50);采用酶联免疫吸附测定(ELISA)法检测血清中FGF-21、Gal-3表达水平;受试者工作特征(ROC)曲线分析血清FGF-21、Gal-3联合对肥胖型PCOS患者IVF-ET治疗后妊娠结局的预测价值。采用Logistic回归分析探索肥胖型PCOS患者IVF-ET治疗后妊娠结局的影响因素。结果与成功组比较,失败组LH、FTI、Glu、INS的水平升高,FSH、SHBG水平、Gn天数降低(P<0.05)。与成功组比较,失败组患者FGF-21水平升高,Gal-3水平降低(t=8.412、8.298,P<0.001、<0.001)。FGF-21、Gal-3联合预测肥胖型PCOS患者IVF-ET治疗后妊娠结局的AUC高于FGF-21、Gal-3单独预测的AUC值(Z=14.317,P<0.001;Z=11.793,P<0.001)。多因素Logistic回归分析结果显示,FGF-21、Gal-3为肥胖型PCOS患者IVF-ET治疗后妊娠结局的影响因素(P<0.05)。结论IVF-ET治疗后妊娠失败的肥胖型PCOS患者血清中FGF-21水平升高、Gal-3水平降低,二者对肥胖型PCOS患者IVF-ET治疗后妊娠结局有一定的预测价值。

清燥救肺汤对特发性肺纤维化肺损伤修复作用及骨桥蛋白、生物标志物和血清FGF-21、HIF-1α的影响

目的:观察清燥救肺汤对特发性肺纤维化患者肺损伤修复作用及生物标志物和血清成纤维细胞生长因子-21(FGF-21)、缺氧诱导因子-1α(HIF-1α)的影响。方法:选择122例特发性肺纤维化患者按随机数字表法分为对照组和观察组各61例。对照组行常规西医治疗,观察组在对照组治疗基础上,同时口服清燥救肺汤。比较两组治疗后临床疗效,治疗前后给予两组中医证候积分评价,给予患者6 min步行距离(6MWT)、圣乔治呼吸问卷(SGRQ)评价,检测患者肺总量(TLC)、一氧化碳弥散量(DLCO)、肺活量(VC)水平,检测患者基质金属蛋白酶-7(MMP-7)、骨桥蛋白、FGF-21、HIF-1α、Ⅱ型肺泡细胞表面抗原(KL-6)、白细胞介素-8(IL-8)水平。结果:治疗后观察组患者总有效率高于对照组(P<0.05);观察组中医证候积分较对照组低(P<0.05);观察组6MWT水平、SGRQ评分较对照组高(P<0.05);观察组TLC、DLCO、VC水平较对照组高(P<0.05);观察组MMP-7、骨桥蛋白、KL-6水平较对照组低(P<0.05);观察组患者FGF-21、HIF-1α水平高于对照组(P<0.05),观察组IL-8水平低于对照组(P<0.05)。结论:清燥救肺汤治疗特发性肺纤维化患者,可提升抗炎作用及肺损伤修复作用,降低生物标志物水平,缓解病情,提升患者运动耐力、生活质量及临床疗效。

血清Nesfatin-1、IGFBP-3、FGF-21联合检测对特发性矮小症的诊断价值

目的探究血清摄食抑制因子(Nesfatin-1)、类胰岛素生长因子结合蛋白3(IGFBP-3)、成纤维细胞生长因子21(FGF-21)联合检测对特发性矮小症(ISS)的诊断价值。方法本研究选取2022年6月至2023年6月期间在本院诊治的85例ISS患儿记为ISS组,另选74例在本院体检的儿童记为对照组,记录两组儿童一般资料并进行比较分析。酶联免疫吸附实验(ELISA)检测受试者血清Nesfatin-1、IGFBP-3、FGF-21;使用原子吸收光谱仪测定受试者血清营养元素钙(Ca)、镁(Mg)、铜(Cu)、铁(Fe)、锌(Zn)的水平。X线骨密度仪检查受试者骨龄(BA)。Pearson相关性分析ISS患儿血清Nesfatin-1、IGFBP-3、FGF-21水平的相关性;多因素Logistic回归分析影响儿童发生ISS的影响因素;受试者工作特征(ROC)曲线分析Nesfatin-1、IGFBP-3、FGF-21水平对ISS的诊断价值;通过Z检验比较曲线下面积(AUC)的差异。结果与对照组相比,ISS组BA、身高、体重、BMI以及IGFBP-3、FGF-21水平较低,Nesfatin-1水平、性发育状态I级人数较高(P<0.05);ISS组患儿Nesfatin-1与IGFBP-3、FGF-21水平呈负相关(r_(Nesfatin-1 vs IGFBP-3)=-0.469,r_(Nesfatin-1 vs FGF-21)=-0.483),IGFBP-3与FGF-21水平呈正相关(r_(IGFBP-3 vs FGF-21)=0.456)(P<0.05);BA、性发育状态、IGFBP-3、FGF-21是儿童发生ISS的独立保护因素,而Nesfatin-1是儿童发生ISS的独立危险因素(P<0.05);Nesfatin-1、IGFBP-3、FGF-21单独诊断ISS的AUC分别为0.831、0.836、0.823,3者联合诊断ISS的AUC为0.928,优于单独及两两联合诊断(P<0.05)。结论ISS患儿血清中Nesfatin-1水平较高,IGFBP-3、FGF-21水平较低,3者是儿童发生ISS的影响因素,联合诊断ISS具有较高价值。

慢性乙型肝炎患者血清GR、FGF-21、DNMT1水平对肝纤维化程度的评估价值

目的探讨慢性乙型肝炎(CHB)患者血清谷胱甘肽还原酶(GR)、成纤维细胞生长因子21(FGF-21)、DNA甲基化转移酶1(DNMT1)水平对肝纤维化程度的评估价值。方法选取2021年5月至2023年5月于永煤集团总医院诊治的80例CHB患者为研究组,另选取同期健康体检者80例作为对照组。比较两组血清GR、FGF-21、DNMT1水平与HBV-DNA载量。依据肝纤维化程度将研究组患者分为无纤维化17例、轻度纤维化20例、中度纤维化25例、重度纤维化18例。分析血清GR、FGF-21、DNMT1水平与HBV-DNA载量、肝纤维化程度、Child-Pugh分级、炎症分级相关性。采用受试者工作特征曲线(ROC)分析血清GR、FGF-21、DNMT1对肝纤维化程度的评估价值。结果研究组血清GR、DNMT1水平高于对照组,FGF-21水平低于对照组(P<0.05);GR、DNMT1与HBV-DNA载量、肝纤维化程度、Child-Pugh分级、炎症分级呈正相关,而FGF-21与HBV-DNA载量、肝纤维化程度、Child-Pugh分级、炎症分级呈负相关(P<0.05);GR、FGF-21、DNMT1联合检测评估肝纤维化程度的AUC大于单项指标评估(P<0.05)。结论CHB患者血清GR、DNMT1水平升高,FGF-21水平降低,联合检测其水平对肝纤维化程度具有一定评估价值。

FGF-21对2型糖尿病并大血管病变兔糖脂代谢的影响

目的探讨FGF-21对2型糖尿病并大血管病变兔糖脂代谢的影响。方法建立2型糖尿病动脉粥样硬化兔模型,实验分为四组,A组:生理盐水治疗组;B组:FGF-21治疗组;C组:胰岛素治疗组;D组:FGF-21+胰岛素治疗组。观察各组治疗前后空腹及餐后2h血糖、4周末血脂的变化。结果 (1)B、C、D组均较A组可明显的降低空腹血糖及餐后2h血糖,三组之间差异无统计学意义(P>0.05),增加FGF-21剂量时,可有效地降低血糖及餐后2h血糖。(2)与A组比较,B、C、D组均可明显降低血浆总胆固醇及低密度脂蛋白胆固醇,升高高密度脂蛋白胆固醇,B、C两组比较差异无统计学意义(P>0.05),D组对血脂调节优于B、C两组,差异有统计学意义(P<0.05)。结论 FGF-21可改善2型糖尿病并大血管病变兔的糖脂代谢,和剂量有一定的相关性;FGF-21可协同胰岛素调节脂类代谢。

血清成纤维细胞生长因子21和脂肪酸结合蛋白4检测对急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗术后心力衰竭的预测价值

目的探究血清成纤维细胞生长因子21(FGF21)和脂肪酸结合蛋白4(FABP4)检测对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后心力衰竭的预测价值。方法选取2020年9月至2022年9月内蒙古医科大学附属医院接诊的113例STEMI患者为研究对象,依据PCI术后1年是否发生心力衰竭(心衰),将其分为心衰组(n=32)和非心衰组(n=81)。应用ELISA法测定血清FGF21、FABP4表达水平,比较两组血清FGF21、FABP4水平,多因素logistic回归分析影响STEMI患者PCI术后发生心力衰竭的相关因素,ROC曲线评估血清FGF21、FABP4水平对STEMI患者PCI术后心力衰竭发生的预测价值。结果心衰组心率次数、C反应蛋白(CRP)、心肌肌钙蛋白(cTnI)、N末端B型利钠肽原(BNP)、利尿剂使用比例均显著高于非心衰组,左心室射血分数(LVEF)显著低于非心衰组(P<0.05)。心衰组血清FGF21、FABP4表达水平均明显高于非心衰组[(228.37±33.07)ng/L比(185.68±25.52)ng/L、(34.26±5.51)ng/ml比(26.87±4.67)ng/ml,t=7.345、7.195,P<0.05]。血清FGF21(95%CI 1.371~8.191)、FABP4(95%CI 1.176~4.090)及发病到至导丝通过时间(95%CI 1.058~8.157)是影响STEMI患者PCI术后发生心力衰竭的危险因素(OR>1,P<0.05),LVEF(95%CI 0.473~0.913)是保护因素(OR<1,P<0.05)。血清FGF21、FABP4单独及二者联合预测STEMI患者PCI术后发生心力衰竭的曲线下面积(AUC)分别为0.828、0.856、0.934,二者联合优于单一(Z二者联合-FGF21=1.971、Z二者联合-FABP4=2.417,P=0.048、P=0.015)。结论STEMI患者PCI术后发生心力衰竭血清FGF21、FABP4水平均明显升高,二者联合对STEMI患者PCI术后发生心力衰竭的风险具有更高的预测价值。

FGF-21通过上调肝脏LDL受体的表达降低血浆中LDL水平

目的成纤维细胞生长因子-21(FGF-21)可降低实验动物血浆中的低密度脂蛋白(LDL)的浓度,但其作用机制尚不清楚,本实验试图通过研究FGF-21对LDLR的调节作用揭示FGF-21调节血浆LDL浓度的机制。方法向谷氨酸钠(MSG)肥胖大鼠连续注射FGF-21蛋白40d后,检测其血浆中LDL的变化,并用荧光定量PCR的方法结合免疫荧光检测FGF-21对肝脏组织中LDLR mRNA及蛋白的影响。结果 MSG肥胖鼠经FGF-21处理,血浆内的LDL降低18%,其肝脏组织中LDLR mRNA含量提高9倍;HepG2细胞内的LDLR mRNA表达量随FGF-21处理时间增加而提高,且呈剂量依赖性;流式细胞仪检测显示,经FGF-21处理后HepG2细胞表面LDLR蛋白数量增加。结论 FGF-21通过增加肝细胞的LDLR表达量从而降低血浆中LDL浓度。

3T3-L1脂肪细胞膜FGF-21结合蛋白的初步鉴定

成纤维细胞生长因子(fibroblast growth factor,FGF)-21是最近发现的1个可以独立调节血糖的细胞因子,有望成为治疗2型糖尿病的备选药物.但是,FGF-21调解血糖的机理尚不十分清楚.为探讨该因子功能受体,应用偶联方法,以3T3-L1脂肪细胞为靶标,以FGF-21为诱饵,在3T3-L1脂肪细胞膜上寻找结合蛋白.结果表明,生物素标记的FGF-21可与脂肪细胞膜蛋白形成分子质量大小约300kD以上两组复合物.竞争试验显示,非标记的FGF-21可与生物素标记的FGF-21竞争、抑制标记的FGF-21参入复合物;应用非标记FGF-21剂量越大,抑制后者参入复合物的程度越强.结果提示,该复合物是FGF-21特异性的.此外,随着生物素标记的FGF-21剂量增加,观察到的标记复合物越多;但是,当FGF-21剂量达12.5mg/L以上时,观察到的复合物数量不再增加.实验结果提示,复合物形成与FGF-21剂量相关;FGF-21特异结合的蛋白质结合位点饱和后,复合物形成量最大.同时,采用FGF受体特异性抑制剂SU5402可特异性抑制FGF-21在3T3-L1脂肪细胞中的促进葡萄糖吸收作用,提示本实验所观察到的FGF-21-膜蛋白复合物可能就是FGF-21-FGF受体.

初诊2型糖尿病患者短期胰岛素泵强化治疗对血浆FGF-21水平及胰岛素敏感性的影响

目的探讨短期胰岛素泵强化治疗对初诊2型糖尿病(T2DM)患者胰岛素敏感性和血浆成纤维细胞生长因子-21(FGF-21)水平的影响。方法采用自身前后对照,运用高胰岛素-正葡萄糖钳夹术评价30例新诊断T2DM患者接受2 w短期胰岛素泵(CSII)强化治疗前后胰岛素敏感性的变化,并采用酶免法测定治疗前后血浆FGF-21水平。结果 T2DM患者血浆FGF-21水平明显高于对照组〔(1.6±0.1)vs(1.1±0.4)μg/L,P<0.01〕。T2DM患者经胰岛素泵强化治疗2 w后,血浆FGF-21水平较治疗前明显下降〔(1.6±0.1)vs(1.3±0.1)μg/L,P<0.05〕。多元逐步回归分析表明,WHR、2 h PBG、SBP及FFA是影响血浆FGF-21水平的独立相关因素(YFGF-21=0.625XWHR+0.034XPBG+0.003XSBP-0.419XFFA+0.626)。结论短期胰岛素泵强化治疗可明显降低T2DM患者血浆FGF-21水平,血浆FGF-21水平与代谢紊乱有关,并可能参与了T2DM的发生和发展。

人源FGF-21在脂肪细胞糖代谢中的作用

近年来研究发现,成纤维细胞生长因子(FGF)-21是一种新的代谢调节因子.为了深入研究人源FGF-21(hFGF-21)的生物活性,本实验利用SUMO高效表达载体,高效表达成熟的hFGF-21,并利用小鼠3T3-L1脂肪细胞检测hFGF-21的糖代谢活性.实验结果表明,hFGF-21可促进脂肪细胞的葡萄糖吸收,且葡萄糖吸收效率呈剂量依赖性.hFGF-21作用4h即可促进脂肪细胞糖吸收,其活性可持续24h以上.hFGF-21与胰岛素共同作用的葡萄糖吸收效果,明显优于它们的单独作用结果,说明hFGF-21与胰岛素发挥协同作用.脂肪细胞经hFGF-21预处理后,显著增加了胰岛素促进脂肪细胞吸收葡萄糖的效率,说明hFGF-21可以增加胰岛素的敏感性.本实验为临床应用hFGF-21治疗糖尿病,增加胰岛素敏感性提供了依据.

FGF-21与罗格列酮钠对棕榈酸诱导的胰岛细胞株凋亡的保护作用及机制研究

目的探讨成纤维细胞生长因子-21(FGF-21)和罗格列酮钠(RO)对棕榈酸(PA)诱导的HIT-T15胰岛细胞凋亡的保护作用和机制。方法①0.25、0.50和1.00 mmol/L的PA干预HIT-T15细胞24 h,流式细胞仪检测细胞凋亡。②在0.50 mmol/L的PA中分别加入FGF-21〔12.50 nmol/L(A)、25.00 nmol/L(B)、50.00 nmol/L(C)〕、1μmol/L RO及3个不同浓度的FGF-21与RO联合,检测细胞凋亡,免疫细胞化学法、Western blot检测各组细胞磷酸化c-jun氨基末端激酶(p-JNK)的表达。结果①PA组细胞凋亡高于对照组(P<0.05)。②FGF-21 A、B、C组能明显降低0.50 mmol/L PA诱导的凋亡(P<0.05),但凋亡率高于对照组(P<0.05)。FGF-21与RO联合干预组的细胞凋亡低于PA组(P<0.05)。联合干预组的细胞凋亡低于单用FGF-21组(P<0.05)。③0.50 mmol/L PA组的p-JNK蛋白表达高于对照组(P<0.05)。不同浓度FGF-21组的p-JNK的表达均低于PA组(P<0.05)。FGF-21与RO联合干预组的p-JNK均低于PA组(P<0.05)。联合干预组p-JNK的表达低于单用FGF-21组(P<0.05)。结论①PA可剂量依赖性的诱导HIT-T15胰岛细胞的凋亡。②FGF-21能抑制PA诱导的HIT-T15胰岛细胞株的凋亡,此机制可能是抑制了p-JNK的表达,并且与RO有协同作用。