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.

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.

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.

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.

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.

Fibroblast growth factor 21(FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB(TFEB)-regulated lipophagy

Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation.However,it has been proved to be associated with post-transplant hyperlipemia.The mechanism behind this is unknown,and it is urgent to explore preventive strategies for hyperlipemia after transplantation.Therefore,we established a hyperlipemia mouse model to investigate the mechanism,by injecting TAC intraperitoneally for eight weeks.After TAC treatment,the mice developed hyperlipemia(manifested as elevated triglyceride(TG)and low-density lipoprotein cholesterol(LDL-c),as well as decreased high-density lipoprotein cholesterol(HDL-c)).Accumulation of lipid droplets was observed in the liver.In addition to lipid accumulation,TAC induced inhibition of the autophagy-lysosome pathway(microtubule-associated protein 1light chain 3β(LC3B)II/I and LC3B II/actin ratios,transcription factor EB(TFEB),protein 62(P62),and lysosomal-associated membrane protein 1(LAMP1))and downregulation of fibroblast growth factor 21(FGF21)in vivo.Overexpression of FGF21may reverse TAC-induced TG accumulation.In this mouse model,the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway.We conclude that TAC downregulates FGF21and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway.Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells

Background Fibroblast growth factor 21 （FGF21） is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.Methods The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein （ox-LDL）, and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells （CMECs） were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.Results The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis （P ＜0.05）.Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.

Protection Effect of Exogenous Fibroblast Growth Factor 21 on the Kidney Injury in Vascular Calcification Rats

Background： Chronic kidney disease （CKD） is closely related to the cardiovascular events in vascular calcification （VC）. However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 （FGF21 ） is an endocrine thctor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases, Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats. Methods： The male Sprague-Dawley rats were divided into three groups： （ 1 ） control group, （2） Vitamin D3 plus nicotine （VDN）-induced VC group, （3） FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases （ALPs） activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of β-Klotho and FGF receptor 1 （FGFR1） protein were measured by enzyme-linked immunosorbent assay （EL1SA）. The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining. Results： The renal lhnction impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% （34.750 ± 4.334 pmol/L vs. 27.630± 2.387pamol/L） and 4.0% （7.038 ± 0.590 mmol/L vs. 6.763 ±0.374 mmol/L; P 〈 0.01 ）, respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% （P 〈 0.01 ） and 11.7% （P 〈 0.05） as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. EL1SA assays showed that the expression of [3-Klotho, a component of FGF21 receptor system was increased in VDN-treated VC rats by 37.4% （6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P 〈 0.01）, indicating an FGF2 l-resistant state. Moreover, FGF21 treatment downregulated the level of β-Klotho in renal tissue by 16.7% （9.054 ± 0.963 pg/mg vs. 7.544± 1.362 pg/mg, P 〈 0.05）. However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration （0.191 ± 0.0376 rig/rag vs. 0.189 ± 0.032 ng/mg rs. 0.181± 0.034 mg/mg; P 〉 0.05）. Conclusions： In the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting offthe vicious circle between VC and kidney injury.

Relationship between fibroblast growth factor 21 and thyroid stimulating hormone in healthy subjects without components of metabolic syndrome

Objective:To determine the relationship between human fibroblast growth factor 21(FGF21)and thyroid stimulating hormone(TSH)by testing the level of FGF21,lipid metabolism,and car-bohydrate metabolism-related indices,as well as the level of TSH,among metabolic syndrome-free patients with normal physical examination results.Methods:An enzyme-linked immunosorbent assay(ELISA)was used to test the levels of serum FGF21 and free fatty acids(FFA)in metabolic syndrome-free patients with normal physi-cal examination results,and electrochemiluminescence(ECLIA)was used to measure TSH,thy-roglobulin antibodies(TGAbs),and thyroid peroxidase antibody(TPOAb)levels.Results:Three hundred fifty-six metabolic syndrome-free patients(116 males and 240 females;average age,43±13 years)with normal physical examination results were enrolled.Among the pa-tients with normal physical examination results,FGF21 had a weak relationship with obesity indices,such as the waist circumference(r=0.110,P=0.038),the waist-to-hip ratio(r=0.119,P=0.025),and the triglycerides level(TG;r=0.302,P=0.000),and a weak relationship with blood lipid levels,such as total cholesterol(TCHO;r=0.113,P=0.012)and low-density lipoprotein-cholesterol(LDL-C;r=0.175,P=0.001),but no relationship with TSH(r=-0.023,P=0.666).In addition,the FGF21 levels in thyroid autoantibody-positive and-negative groups were not significantly different.Conclusion:Among the metabolic syndrome-free patients with normal physical examina-tion results,FGF21 has no apparent relationship with TSH or thyroid autoimmunity.

Fibroblast growth factor 21 and dietary interventions: what we know and what we need to know next

Dietary interventions include the change of dietary styles,such as fasting and dietary or nutrient restrictions;or the addition of plant-derived compounds(such as polyphenols known as curcumin,resveratrol,or anthocyanin,or other nutraceuticals)into the diet.During the past a few decades,large number of studies have demonstrated therapeutic activities of these dietary interventions on metabolic and other diseases in human subjects or various animal models.Mechanisms underlying those versatile therapeutic activities,however,remain largely unclear.Interestingly,recent studies have shown that fibroblast growth factor 21(FGF21),a liver-derived hormone or hepatokine,mediates metabolic beneficial effects of certain dietary polyphenols as well as protein restriction.Here I have briefly summarized functions of FGF21,highlighted related dietary interventions,and presented literature discussions on role of FGF21 in mediating function of dietary polyphenol intervention and protein restriction.This is followed by presenting my perspective view,with the involvement of gut microbiota.It is anticipated that further breakthroughs in this field in the near future will facilitate conceptual merge of classical medicine and modern medicine.

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。

血清成纤维细胞生长因子-21、亚甲基四氢叶酸还原酶基因多态性与妊娠期亚临床甲状腺功能减退症的相关性

目的 探究血清成纤维细胞生长因子-21(FGF-21)、亚甲基四氢叶酸还原酶(MTHFR)基因多态性与妊娠期亚临床甲状腺功能减退症(SCH)的相关性。方法 选取2022年7月至2023年7月山西省临汾市人民医院收诊的妊娠期SCH患者106例为SCH组,另选取院内同期孕检的健康妊娠期女性106例为健康组。收集两组病历资料,筛查SCH的相关因素,分析血清FGF-21、MTHFR基因多态性对SCH发生的评估效能。结果 SCH组的空腹血糖、血清促甲状腺素(TSH)、FGF-21高于健康组(P<0.05);两组CC、CT、TT基因型分布频率比较,差异有统计学意义(P<0.05)。SCH组T等位基因分布频率高于健康组(P<0.05)。多因素分析结果显示,血清FGF-21(OR=3.330,95%CI:1.138~9.743)、MTHFR基因多态性(OR=4.104,95%CI:1.403~12.008)是SCH发生的影响因素(P<0.05)。血清FGF-21、MTHFR基因多态性单一及联合诊断SCH发生的受试者操作特征曲线下面积分别为0.738、0.670、0.851。结论 血清FGF-21水平升高、MTHFR基因TT基因型的妊娠期女性SCH发生风险更高,两项联合具有一定的诊断价值。

利用1型糖尿病小鼠模型分析犬成纤维生长因子21的长效降糖效果

本研究分别将Fc片段、穿膜肽R11和穿膜肽TAT与犬成纤维生长因子21(canine fibroblast growth factor 21,cFGF-21)相连构建了3种融合蛋白,旨在探讨cFGF-21对1型糖尿病的长效降糖作用。用链脲佐菌素(STZ)建立1型糖尿病小鼠模型,随后分别用cFGF-21、R11-cFGF-21、Fc-cFGF-21和TAT-cFGF-21治疗。治疗分为3个阶段:1)每天给药一次(第1~14天);2)每3 d给药一次(第15~29天);3)每5 d给药一次(第30~44天)。在治疗过程中,每隔3 d检测一次小鼠血糖,在每阶段结束时检测试验小鼠12 h内血糖波动。试验结束前,对所有小鼠进行口服葡萄糖耐量试验。通过ELISA法检测小鼠血清中炎症相关因子IL-10、IL-1β、IL-17A和抗炎因子IL-10表达水平。通过Real-time PCR检测肝、脂肪、肠和肾等组织中的糖代谢相关因子的转录水平。试验结束后,对所有小鼠进行糖基化血红蛋白(HbA1c)、血脂四项和肝功能、血清胰岛素和HbA1c检测并对小鼠胰腺组织进行病理分析。结果显示:在治疗的第一阶段,与cFGF-21组相比,TAT-cFGF-21降糖效果明显降低,R11-cFGF-21和Fc-cFGF-21组没有显著差异;在治疗的第二、三阶段,与cFGF-21组相比,TAT-cFGF-21组血糖明显上升,R11-cFGF-21和Fc-cFGF-21组可在给药3~5 d内能将血糖控制在更低的水平。治疗8周后,与cFGF-21组相比,R11-cFGF-21和Fc-cFGF-21组口服葡萄糖耐量(OGTT)和血脂紊乱明显改善,糖化血红蛋白(HbA1c)接近正常水平,肝损伤明显修复,而TAT-cFGF-21组与cFGF-21组没有明显差距。此外,ELISA检测和HE染色结果显示,相较cFGF-21和TAT-cFGF-21组,R11-cFGF-21和Fc-cFGF-21组氧化应激和炎症反应得到显著改善且胰岛β细胞修复效果明显。经R11和Fc修饰的cFGF-21长效降糖能力的显著增加,而TAT-cFGF-21长期的降血糖能力较弱。此外,经R11和Fc修饰的cFGF21能显著改善氧化应激、胰腺炎症和脂质代谢,修复肝损伤和胰岛β细胞,治疗效果明显优于cFGF21。

FGF−21、IMA、MCP−1与急性心肌梗死患者预后的关系

目的 研究成纤维细胞生长因子-21 (fibroblast growth factor 21,FGF-21)、缺血修饰白蛋白(ischemia modified albumin,IMA)、单核细胞趋化蛋白-1 (monocyte chemotactic protein-1,MCP-1)与急性心肌梗死(acute myocardial Infarction,AMI)患者预后的关系。方法 选择本院2017年5月-2020年7月诊治的110例AMI患者,根据患者预后情况分为预后不良组和预后良好组,收集患者临床资料,分析其血清FGF-21、IMA、MCP-1水平与AMI患者预后的关系以及诊断主要不良心血管事件(major adverse cardiovascular event,MACE)发生的效能。结果 预后良好组患者血清FGF-21、IMA、MCP-1水平低于预后不良组,差异有统计学意义(P<0.05);血清FGF-21、IMA、MCP-1水平3者联合预测预后的ROC曲线下面积(area under curve,AUC)以及敏感度最高(P<0.05);不同血清FGF-21、IMA、MCP-1水平患者MACE发生率比较,差异有统计学意义(P<0.05);Cox单因素以及多因素分析结果显示,FGF-21>150.12 ng/L、IMA> 75.78 U/mL、MCP-1> 49.67 pg/mL、肌酸激酶-同工酶(CK-MB)> 35 U/L以及心肌肌钙蛋白Ⅰ(cTnⅠ)> 75.78 U/mL均是影响AMI患者预后不良的独立危险因素(P<0.05)。结论 血清FGF-21、IMA、MCP-1水平均可较好地预测AMI患者预后不良的发生,且三者联合预测效能更高,同时血清FGF-21、IMA、MCP-1水平增高与MACE的发生密切相关,是AMI患者预后不良的危险因素。

非酒精性脂肪肝患者血清FGF21水平变化与颈动脉粥样硬化斑块发生的相关性

目的:探讨非酒精性脂肪肝(NAFLD)患者血清成纤维细胞生长因子21(FGF21)水平变化及与颈动脉粥样硬化斑块发生的相关性。方法:选取2023-01-2023-09确诊的NAFLD患者131例,根据是否存在颈动脉粥样硬化斑块分为无斑块组(n=59)和斑块组(n=72),选取同期体检健康者39例为对照组。检测所有对象血清尿酸(UA)、低密度脂蛋白胆固醇(LDL-C)、小而密低密度脂蛋白胆固醇(sdLDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、总胆固醇(TC)和FGF21水平并比较组间差异。Logistic回归分析FGF21与NAFLD患者颈动脉粥样硬化斑块发生的相关性。结果:与对照组比较,无斑块组和斑块组患者UA、TC、TG、LDL-C、sdLDL-C和FGF21水平均升高,HDL-C水平降低(P<0.05或P<0.01);与无斑块组比较,斑块组LDL-C、sdLDL-C和FGF21升高(P<0.05或P<0.01)。Logistic回归分析显示,在充分调整协变量后,血清FGF21升高与NAFLD患者动脉粥样硬化斑块发生呈正相关。结论:血清FGF21是NAFLD患者颈动脉粥样硬化斑块发生的危险因素。

FGF21类似物通过抑制线粒体自噬促进白色脂肪细胞“棕色化”的机制研究

目的:探讨成纤维细胞生长因子21(FGF21)长效类似物PF-05231023通过抑制白色脂肪组织(WAT)线粒体自噬对WAT“棕色化”的作用以及其中涉及的分子机制。方法:(1)使用高脂饮食(HFD)复制小鼠肥胖模型,18只C57BL/6J小鼠被分为3组:正常对照(NC)组、HFD组和PF-05231023干预(PF+HFD)组,每组6只。饲养12周后麻醉小鼠,摘眼球取血,分离血清,检测小鼠血清中的总胆固醇(TC)、甘油三酯(TG)、低密度胆固醇脂蛋白(LDL-C)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的水平;收集小鼠腹股沟WAT(iWAT)、附睾WAT(eWAT)和肝脏,一部分组织用于Western blot实验,检测“棕色化”相关指标解偶联蛋白1(Ucp-1)和过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)以及线粒体自噬相关指标PTEN诱导激酶1(Pink1)、parkin、beclin-1和微管相关蛋白1轻链3-II(LC3-II)蛋白表达水平,另一部分固定于多聚甲醛中,用于后续HE和免疫组织化学染色。(2)3T3-L1细胞采用经典的“鸡尾酒”方法诱导成为成熟的脂肪细胞。CCK-8法检测不同浓度PF-05231023干预对细胞活力的影响。用PF-05231023干预3T3-L1细胞48 h,收集细胞团块用于Western blot实验检测“棕色化”相关指标Ucp-1和PGC-1α以及线粒体自噬相关指标Pink1、parkin、beclin-1和LC3-II蛋白表达水平。油红O染色检测细胞积累。免疫荧光染色检测Ucp-1蛋白含量。随后将3T3-L1细胞分为正常组、PF-05231023干预组、Pink1激动剂MTK458干预组和MTK458+PF-05231023干预组,收集细胞团块用于Western blot实验检测上述指标。结果:(1)PF-05231023干预不影响小鼠能量摄入并且能降低HFD诱导肥胖小鼠的体重、肝重和脂肪重量(P<0.05),降低脂质积累(TC、TG和LDL-C)和肝损伤(ALT和AST)并减轻肝脏空泡样变性和脂肪细胞面积大小(P<0.05);(2)与HFD组相比PF-05231023干预增加了iWAT和eWAT中Ucp-1和PGC-1α蛋白表达水平(P<0.01),免疫组织化学染色结果中PF-05231023干预组比HFD组Ucp-1蛋白含量更高;(3)PF-05231023干预可呈剂量依赖式增加诱导成熟的3T3-L1细胞中Ucp-1和PGC-1α的蛋白表达水平(P<0.01),减少细胞脂质积累,免疫荧光染色结果显示PF-05231023干预后诱导成熟的3T3-L1细胞中Ucp-1蛋白含量增加;(4)PF-05231023干预可抑制iWAT、eWAT和诱导成熟的3T3-L1细胞中线粒体自噬相关指标Pink1、parkin、beclin-1和LC3-II蛋白表达水平(P<0.05);(5)MTK干预可增加Pink1、parkin和beclin-1和LC3-II蛋白表达水平,增加Ucp-1蛋白表达水平,与MTK干预组比,MTK和PF-05231023共同干预后可部分降低Pink1、parkin、beclin-1和LC3-II蛋白表达水平,部分恢复Ucp-1蛋白表达水平(P<0.01)。结论:(1)PF-05231023干预能够改善HFD诱导小鼠的肥胖和相关代谢紊乱;(2)PF-05231023干预能够抑制WAT和诱导成熟的3T3-L1细胞线粒体自噬,并通过抑制线粒体自噬促进“棕色化”;(3)其机制可能与抑制Pink1-parkin信号通路有关。

血清FGF21和脂联素与心肌梗死后急性心力衰竭的相关性研究

目的:探讨血清成纤维细胞生长因子21(FGF21)和脂联素(APN)与急性心肌梗死(AMI)后急性心力衰竭(AHF)的相关性。方法:依据中国心力衰竭诊断和治疗指南诊断标准,纳入140例符合纳入和排除标准且首次诊断为AMI的患者,试验组包括急性非ST段抬高型心肌梗死(NSTEMI)组、NSTEMI合并AHF组、急性ST段抬高型心梗(STEMI)组、STEMI合并AHF组,每组35例。纳入同期在医院进行体检者70名为对照组。用ELISA法测定每组受检者血清FGF21与血清APN的含量,应用相关性分析判断两指标与AMI及AMI后AHF的相关性。结果:与未合并AHF组相比,合并AHF组血清FGF21含量升高(Z=-3.20),APN含量降低(Z=-2.05),差异均有统计学意义(均P<0.05)。与对照组相比,试验组血清FGF21含量升高(H=165.50),血清APN含量降低(H=178.70),差异均有统计学意义(均P<0.001)。相关性分析显示,血清FGF21含量与AMI后AHF发病率呈正相关(r=0.57,P<0.001),血清APN含量与AMI后AHF发病率呈负相关(r=-0.82,P<0.001)。结论:血清FGF21、APN含量与AMI后AHF发病率显著相关。

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。

单核细胞/高密度脂蛋白胆固醇比值、成纤维细胞生长因子21、C肽表达水平与2型糖尿病性骨质疏松症相关性分析

目的:分析单核细胞/高密度脂蛋白胆固醇比值(MHR)、成纤维细胞生长因子21(FGF21)、C肽表达水平与2型糖尿病(T2DM)性骨质疏松症患者的相关性。方法:选取收治的T2DM性骨质疏松症患者90例为研究组,选取同期治疗的单纯T2DM患者57例为对照组。比较两组一般资料、骨钙素(BGP)、25羟基维生素D3[25(OH)D3]、Ⅰ型前胶原N端前肽(PINP)、MHR、FGF21、C肽水平差异;采用Spearman秩相关分析MHR、FGF21、C肽与患者骨代谢指标[BGP、25(OH)D3、PINP]的相关性;多元Logistic回归分析影响T2DM患者发生骨质疏松症的危险因素;绘制ROC曲线评价MHR、FGF21、C肽及三者联合检测对T2DM患者发生骨质疏松症的诊断价值。结果:研究组女性占比率高于对照组(P<0.05);相较于对照组,研究组MHR水平更高,而BGP、25(OH)D3、PINP、FGF21及C肽水平更低(均P<0.05);Spearman相关性分析显示,MHR与BGP、25(OH)D3、PINP均呈负相关(均P<0.05),FGF21及C肽与BGP、25(OH)D3、PINP均呈正相关(均P<0.05);多元Logistc分析显示,MHR是T2DM患者发生骨质疏松症的危险因素(P<0.05);FGF21及C肽是T2DM患者发生骨质疏松症的保护因素(均P<0.05);ROC曲线显示,MHR、FGF21、C肽及三者联合检测预测T2DM患者发生骨质疏松的曲线下面积分别为0.894、0.759、0.810、0.969。结论:T2DM骨质疏松症患者MHR水平上升,FGF21、C肽水平下降,且上述指标与患者骨质疏松密切相关,通过联合检测MHR、FGF21、C肽三者水平对于预测T2DM患者发生骨质疏松具有较好的应用价值。

血清FGF21联合NT-proBNP预测第二代药物洗脱支架植入术后支架内再狭窄的临床研究

目的观察血清成纤维细胞生长因子(FGF)-21与第二代药物洗脱支架(DES)植入术后支架内再狭窄(ISR)的关系以及联合N-末端脑钠肽前体(NT-proBNP)预测ISR的价值。方法选取2019年1月—2021年6月海南医学院第二附属医院心血管内科一区接受二代DES经皮冠状动脉介入(PCI)的冠心病(CAD)患者175例,并在PCI术前采集外周血样本,通过酶联免疫吸附测定法检测血清FGF21水平。在PCI后9~24个月复查冠状动脉造影,并根据是否发生ISR分为ISR组32例和非ISR组143例。应用广义加性模型(GAM)探讨FGF-21与ISR风险的关系,多因素Logistic回归分析影响CAD患者DES植入术后2年ISR风险的临床因素,受试者工作特征(ROC)曲线分析其预测价值。结果ISR组血清FGF21水平高于非ISR组(Z=7.081,P<0.001)。多因素Logistic回归分析结果显示,支架总长度≥38 mm、NT-proBNP和FGF21升高是CAD患者DES植入术后2年ISR风险增加的独立预测因素[OR(95%CI)=1.072(1.040~1.106)、1.004(1.002~1.007)、1.038(1.021~1.056)]。血清FGF21水平和DES植入术后2年ISR发生率的拟合曲线结果显示两者呈正相关(r=0.508,P<0.001)。血清FGF21预测DES植入术后2年ISR风险的曲线下面积(AUC)为0.891,NT-proBNP的AUC为0.739,且FGF21联合NT-proBNP预测的AUC为0.966(P<0.001)。结论血清FGF21是接受二代DES PCI治疗的CAD患者2年ISR风险的独立危险因素。联合FGF21和NT-proBNP对ISR的预测潜力具有更高价值。