Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation

The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.

Changes in expression and secretion patterns of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway molecules during murine neural stem/progenitor cell differentiation in vitro

In the present study, we investigated the dynamic expression of fibroblast growth factor 8 and Sonic Hedgehog signaling pathway related factors in the process of in vitro hippocampal neural stem/progenitor cell differentiation from embryonic Sprague-Dawley rats or embryonic Kunming species mice, using fluorescent quantitative reverse transcription-PCR and western blot analyses. Results demonstrated that the dynamic expression of fibroblast growth factor 8 was similar to fibroblast growth factor receptor 1 expression but not to other fibroblast growth factor receptors. Enzyme-linked immunosorbent assay demonstrated that fibroblast growth factor 8 and Sonic Hedgehog signaling pathway protein factors were secreted by neural cells into the intercellular niche. Our experimental findings indicate that fibroblast growth factor 8 and Sonic Hedgehog expression may be related to the differentiation of neural stem/progenitor cells.

Growth differentiation factor-15 is a prognostic marker in patients with intermediate coronary artery disease

Background Growth differentiation factor-15(GDF-15)is involved in multiple processes that are associated with coronary artery disease(CAD).However,little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD.This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD.Methods A prospective study was performed based on 541 patients with intermediate CAD(20%–70%).GDF-15 of each patient was determined in a blinded manner.The primary endpoint was major adverse cardiac event(MACE),which was defined as a composite of all-cause death,nonfatal myocardial infarction,revascularization and readmission due to angina pectoris.Results After a median follow-up of 64 months,504 patients(93.2%)completed the follow-up.Overall,the combined endpoint of MACE appeared in 134 patients(26.6%)in the overall population:26 patients died,11 patients suffered a nonfatal myocardial infarction,51 patients underwent revascularization,and 46 patients were readmitted for angina pectoris.The plasma levels of GDF-15(median:1172.02 vs.965.25 pg/m L,P=0.014)were higher in patients with ischemic events than those without events.After adjusting for traditional risk factors,higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE(HR=1.244,95%CI:1.048–1.478,Quartile 4 vs.Quartile 1,P=0.013).Conclusions The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.

GROWTH DIFFERENTIATION FACTOR-5 STIMULATES THE GROWTH AND ANABOLIC METABOLISM OF ARTICULAR CHONDROCYTES

Objective To observe the effect of growth differentiation factor-5 (GDF-5) on the growth and anabolic metabolism of articular chondrocytes. Methods The articular chondrocytes isolated from rats were treated with various concentrations of rmGDF-5, and the growth of chondrocytes measured by MTT assay, the cellular cartilage matrices formation detected sulfated glycosaminoglycan by Alcian blue staining and type Ⅱcollagen by RT-PCR. Results After 7 days culture, MTT assay showed that GDF-5 enhanced the growth of chondrocytes in a dose-dependent manner, RT-PCR showed that GDF-5 clearly induced the synthesis of type Ⅱ collagen because of the col2a1 mRNA band more and more strong in a dose-dependent. Chondrocytes were cultured with GDF-5 for 14 days, the intensity of Alcian blue staining was greatly enhanced, especially, at a high concentration of 1000ng/mL, and GDF-5 enhanced the accumulation of the Alcian blue-stainable material in a concentration-dependent manner and in a does-dependent manner. Conclusion GDF-5 enhanced the growth of mature articular chondrocytes, and stimulated the cellular cartilage matrices formation in mono-layer culture.

Identification of cytokines involved in hepatic differentiation of mBM-MSCs under liver-injury conditions

AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.

BMP-4 induced proliferation and oriented differentiation of rat hepatic oval cells into hepatocytes

Objective:To explore the role of bone morphogenetic protein 4(BMP-4) in hepatic progenitor cells(HPCs).Methods:The effect of BMP-4 on rat hepatic oval cells was examined by using the WB-F344 rat hepatocytic epithelial stem-cell-like cell line.This hepatocytic cell line could exert various hepatocytc functions including the secretion of albumin and urea.Immunohistochemistry was used to examine the effects of BMP-4 and its antagonist,Noggin,on the proliferation and differentiation of these cells,cellular uptake and excretion of indocyanine green,the periodic acid-schiff(PAS) assay for glycogen storage and the expression of hepatic markers.Results:Our results showed for the first time that BMP-4 may acted as a potential inducer of hepatic differentiation in rat hepatic oval cells.Conclusions:This cell source offers a much-needed attractive and expandable source for future investigations of drug screening,stem cell technologies and cellular transplantation,in a society with increasing levels of liver disease and damage.

An effective inducer of dopaminergic neuron-like differentiation

Rat bone marrow-derived mesenchymal stem cells were cultured and passaged in vitro. After induction with basic fibroblast growth factor for 24 hours, passage 3 bone marrow-derived mesenchymal stem cells were additionally induced into dopaminergic neurons using three different combinations with basic fibroblast growth factor as follows： 20% Xiangdan injection; ali-trans retinoic acid ＋ glial-derived neurotrophic factor; or sonic hedgehog ＋ fibroblast growth factor 8. Results suggest that the bone marrow-derived mesenchymal stem cells showed typical neuronal morphological characteristics after induction. In particular, after treatment with sonic hedgehog ＋ fibroblast growth factor 8, the expressions of nestin, neuron-specific enolase, microtubule- associated protein 2, tyrosine hydroxylase and vesicular monoamine transporter-2 in cells were significantly increased. Moreover, the levels of catecholamines in the culture supernatant were significantly increased. These findings indicate that Xiangdan injection, all-trans retinoic acid ＋ glial-derived neurotrophic factor, and sonic hedgehog ＋ fibroblast growth factor 8 can all induce dopaminergic neuronal differentiation from bone marrow-derived mesenchymal stem cells. In particular, the efficiency of sonic hedgehog ＋ fibroblast growth factor 8 was highest.

Effect of the gap junction blocker 1-heptanol on chondrogenic differentiation of mouse bone marrow mesenchymal stem cells in vitro

Objective：To investigate the effect of the gap junction blocker 1-heptanol on the in vitro chondrogenic differentiation of mouse bone marrow mesenchymal stem cells（MSCs） following induction by GDF-5. Methods：MSCs were isolated from mouse bone marrow and cultured in vitro. After 3 passages cells were induced to undergo chondrogenic differentiation with recombinant human GDF-5（100 ng/ml）, with or without 1-heptanol（2.5 la mol/L）. The effect of 1-heptanol on MSCs proliferation was investigated using the MTT assay. Type II collagen mRNA and protein were examined by RT-PCR and immunocytochemistry respectively, and the sulfate glycosaminoglycan was assessed by Alcian blue dye staining. Connexin43（Cx43） protein was examined by western blotting. Results：GDF-5 induced proliferation and chondrogenic differentiation of MSCs. While 1-heptanol treatment had no effect on this proliferation, it inhibited the expression of both type II collagen mRNA and protein. The Alcian blue staining revealed that 1-heptanol also inhibited the deposition of the typical cartilage extracellular matrix promoted by recombinant GDF-5. Western blotting demonstrated that 1-heptanol had no effect on the expression of Cx43. Conclusion：These results suggest that mouse bone marrow MSCs can be differentiated into a chondrogenic phenotype by GDF- 5 administration in vitro. While the gap junction blocker, 1-heptanol, did not reduce gap junction Cx43, these intercellular communication pathways clearly played an important functional role in GDF-5-induced cartilage differentiation.

Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons

Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.It is widely distributed in the central and peripheral nervous systems.Whether and how GDF-15 modulates nociceptive signaling remains unclear.Behaviorally,we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats.Electrophysiologically,we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia(DRG)neurons.Furthermore,GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents,and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction.GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels,suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel.Immunohistochemistry results showed that activin receptor-like kinase-2(ALK2)was widely expressed in DRG medium-and small-diameter neurons,and some of them were Nav1.8-positive.Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors.Inhibition of PKA and ERK,but not PKC,blocked the inhibitory effect of GDF-15 on Nav1.8 currents.These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK,which mediate the peripheral analgesia of GDF-15.

肌肉生长抑制素GDF-8

肌肉生长抑制素GDF-8属于TGF-β超家族一员,最早研究发现在骨骼肌中特异性表达,是骨骼肌生长发育的抑制因子。对该因子的基因定位、结构、功能和作用机制进行综述,并阐明其在运动实践中的应用前景。

6周负重跑训练和补充大豆多肽对D-半乳糖衰老大鼠骨骼肌IGF-I mRNA和GDF-8 mRNA表达的影响

目的:探讨6周负重跑训练和补充大豆多肽对衰老大鼠骨骼肌IGF-I mRNA和GDF-8 mRNA表达的影响。方法:56只雄性SD大鼠随机分为7组:成年组,模型组,大负重组,小负重组,补肽组,补肽+大负重组和补肽+小负重组。除成年组外,其余各组大鼠采用6周D-半乳糖皮下注射复制亚急性骨骼肌衰老模型,同时按分组分别施加大(70%最大负重)、小(30%最大负重)两种负重方式的跑台训练或/和补充15%大豆多肽的干预。6周实验结束后禁食12小时,处死所有大鼠,无菌取材,测试骨骼肌IGF-I mRNA和GDF-8mRNA表达量。结果:与成年组相比,模型组骨骼肌IGF-I mRNA表达显著下降(P<0.01),GDF-8 mRNA表达显著升高(P<0.01),负重或补肽单独干预及其联合干预均可有效逆转以上趋势(P<0.01),并且负重和补肽两者具有显著交互作用。结论:负重跑训练或补充大豆多肽干预,可有效改善衰老大鼠骨骼肌IGF-I mRNA低表达和GDF-8 mRNA高表达,并且两种手段联合运用也可达到相同效果。

诱导骨髓间充质干细胞成肌分化时GDF-8表达的变化

目的探讨大鼠骨髓间充质干细胞(BMSCs)在体外诱导成肌分化时转化生长因子-8(GDF-8)表达的变化。方法原代培养后扩增的第5代BMSCs以5-氮胞苷(5-Azc)进行成肌诱导分化,用免疫荧光、逆转录定量聚合酶链反应(RT-PCR)、免疫印迹(Western Blot)检测GDF-8的表达。结果体外诱导BMSCs成肌分化时免疫荧光检测发现,在不同时间点于绝大多数细胞的胞浆内都有明显的GDF-8表达,而没有用5-Azc处理的BMSCs则无表达,RT-PCR和Western Blot的检测也支持免疫组织化学的结果。结论在促使BMSCs向肌细胞分化的同时,细胞内同时也有抑制成肌分化的负性调节因子GDF-8的表达。

小鱼际■法对骨骼肌钝性损伤家兔生长分化因子8与F-肌动蛋白的影响

目的研究小鱼际■法对家兔钝性损伤骨骼肌内生长分化因子8 (growth differentiation factor,GDF-8)、F-肌动蛋白(F-actin)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)与白细胞介素6(interleukin-6,IL-6)表达的影响,探讨小鱼际■法治疗骨骼肌损伤的生理过程。方法选取18只3月龄新西兰大耳白兔,雌雄各半,随机分为空白组、模型组、治疗组,每组各6只。空白组除正常饲养外不进行任何处理;模型组通过自制重锤击打右后肢股四头肌构建骨骼肌钝伤模型,其后正常饲养;治疗组与模型组进行相同的造模处理,并在造模成功后第5天开始对损伤处进行小鱼际■法治疗,每天2次,每次5分钟,持续治疗3天。饲养第8天取材,取受损处肌肉组织(空白组取相同位置),使用苏木精—伊红(hematoxylin-eosin,HE)染色技术观察肌肉组织形态,使用Western Blot法检测所取组织中GDF-8与F-肌动蛋白的表达情况,使用ELISA法检测组织中炎症因子TGF-β1和IL-6的表达情况。结果 HE染色结果显示,与空白组相比,模型组有严重的肌肉纤维损伤,表明骨骼肌损伤模型造模成功;与模型组相比,治疗组的肌肉肌纤维恢复状态更好,肌肉受损程度更低,炎性细胞与不规则的结缔组织更少。Western Blot法检测结果表明,与空白组相比,模型组受损肌肉中GDF-8与F-肌动蛋白指标显著升高;与模型组相比,治疗组受损肌肉中GDF-8与F-肌动蛋白指标明显降低。ELISA法检测结果表明,模型组TGF-β1指标高于空白组,治疗组TGF-β1相比于模型组又有明显上升;模型组、治疗组IL-6含量均高于空白组,治疗组IL-6含量相比于模型组有明显下降。所有组间指标差异均具有统计学意义(P<0.05)。结论使用小鱼际■法治疗骨骼肌钝伤家兔能有效加速骨骼肌的恢复,并减缓受伤骨骼肌恢复过程中的纤维化程度与炎症反应,提升恢复后的肌肉运动能力。

脓毒症并发急性肾损伤患者血清MCP-1、MFG-E8、sCD14-ST的表达及临床意义

目的研究脓毒症并发急性肾损伤(AKI)患者血清单核细胞趋化蛋白-1(MCP-1)、乳脂球表皮生长因子8(MFG-E8)、可溶性白细胞分化抗原14亚型(sCD14-ST)的表达水平并探讨其临床意义。方法将2018年1月至2020年10月大连医科大学附属第二医院重症医学科收治的120例脓毒症患者纳入研究,将其按照是否并发AKI分为AKI组57例和非AKI组63例。比较两组患者的临床基线资料和血清MCP-1、MFG-E8、sCD14-ST水平,采用多因素Logistic回归分析明确脓毒症并发AKI与各项因素的关系,并以受试者工作特征(ROC)曲线分析血清MCP-1、MFG-E8、sCD14-ST诊断脓毒症并发AKI的效能。结果AKI组患者的血清MCP-1、sCD14-ST水平分别为(548.32±134.29)ng/mL、(1542.19±245.23)pg/mL,明显高于非AKI组的(346.28±103.56)ng/mL、(551.32±123.49)pg/mL,而MFG-E8水平为(7.62±2.10)pg/mL,明显低于非AKI组的(15.12±2.37)pg/mL,差异均有统计学意义(P<0.05);AKI组患者的高血压病史、肺部感染人数占比明显高于非AKI组,且急性生理与慢性健康状况评估Ⅱ(APACHEⅡ)评分和动脉血乳酸、尿素氮(BUN)、血肌酐(Scr)水平明显高于非AKI组,而氧合指数明显低于非AKI组,差异均有统计学意义(P<0.05);经多因素Logistic回归分析发现,高血压病史、肺部感染、APACHEⅡ评分、动脉血乳酸以及血清MCP-1、sCD14-ST水平均是脓毒症并发AKI的独立危险因素(P<0.05),而血清MFG-E8水平是脓毒症并发AKI的保护性因素(P<0.05);血清MCP-1、MFG-E8、sCD14-ST联合检测诊断脓毒症并发AKI的曲线下面积、灵敏度、特异度、约登指数均高于上述三项指标单独诊断,差异均有统计学意义(P<0.05)。结论脓毒症并发AKI患者均存在血清MCP-1、sCD14-ST明显高表达,而MFG-E8则明显低表达,且联合检测可能为临床脓毒症并发AKI的诊断提供可靠依据。

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study

Background:Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers.The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15(GDF-15)and N-terminal prohormone of brain natriuretic peptide(NT-proBNP)in assessing hospitalized patients with acute heart failure(AHF).Methods:In total,260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016.Medical history and blood samples were collected within 24 h after the admission.The primary endpoint was the all-cause mortality within 1 year.The patients were divided into survival group and death group based on the endpoint.With established mortality risk factors and serum GDF-15 level,receiver-operator characteristic(ROC)analyses were performed.Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.Results:Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors(P<0.001).In ROC analyses,area under curve(AUC)for GDF-15 to predict 1-year mortality was 0.707(95%confidence interval[CI]:0.648–0.762,P<0.001),and for NT-proBNP was 0.682(95%CI:0.622–0.738,P<0.001).No statistically significant difference was found between the two markers(P=0.650).Based on the optimal cut-offs(GDF-15:4526.0 ng/L;NT-proBNP:1978.0 ng/L),the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction(AUC=0.743,95%CI:0.685–0.795,P<0.001).Conclusions:GDF-15,as a prognostic marker in patients with AHF,is not inferior to NT-proBNP.Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.Clinical trial registration:ChiCTR-ONC-12001944,http://www.chictr.org.cn.

Transforming growth factor-β1 involved in urotensin Ⅱ-induced phenotypic differentiation of adventitial fibroblasts from rat aorta

Background Urotensin Ⅱ （UⅡ） is a new vasoconstrictive peptide that may activate the adventitial fibroblasts.Transforming growth factor-β1 （TGF-β1） is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-β1 is involved in UⅡ-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.Methods Adventitial fibroblasts were prepared by the explant culture method. TGF-β1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of α-smooth nuscle actin （α-SM-actin）, the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR （real-time RT-PCR） and Western blotting, respectively.Results UⅡ stimulated the secretion of TGF-β1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% （P ＜0.01）, than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10-8 mol/L of UⅡ （P ＜0.01）, which was increased by 59.9%,compared with in the control group （P ＜0.01）. The secretion of TGF-β1 induced by UⅡ was significantly blocked by SB-710411 （10-7 mol/L）, a specific antagonist of UⅡ receptor. In addition, both UⅡ （10-8 mol/L） and TGF-β1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UⅡ was inhibited by the specific neutralizing antibody （20 μg/ml） of TGF-β1, while the α-SM-actin expression stimulated by TGF-β1 （20 ng/ml）was inhibited by SB-710411 （10-7 mol/L）, the UⅡ receptor antagonist.Conclusion This study suggests that UⅡ could induce TGF-β1 secretion in adventitial fibroblasts via UT activation, and TGF-β1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UⅡ, and TGF-β1 signaling might be one of the important pathways by which UⅡ is involved in vascular fibrosis.

甲状腺功能减低症患者血清IGF-1和IL-8联合检测的价值分析

目的:观察研究甲状腺功能减低症患者血清胰岛素样生长因子-1(IGF-1)及白介素-8(IL-8)的检验结果。方法:选择甲状腺功能减低症患者50例为试验组,以50例健康者为对照组。被检者均进行IGF-1和IL-8检查。结果:试验组患者IGF-1低于对照组(P<0.05),试验组IL-8水平低于对照组(P<0.05)。结论:甲状腺功能减低症患者的血清IGF-1和IL-8均有明显降低,两指标有助于对患者进行鉴别诊断。

生长分化因子8调控女性生殖生理活动及生殖疾病相关分子机制的研究进展

生长分化因子8(GDF-8)又称为肌肉生长抑制素,属于转化生长因子β(TGF-β)超家族成员之一,广泛参与人体各种生理功能。GDF-8在女性卵巢、子宫与胎盘中均有表达。近年来,GDF-8在女性生殖系统中的重要性逐渐被揭示出来。在生殖生理方面,GDF-8参与卵泡发育、排卵、卵巢类固醇激素生成、胚胎着床与胎盘发育等一系列过程;在生殖病理方面,GDF-8不仅参与女性生殖疾病发生,如多囊卵巢综合征(PCOS)、子宫肌瘤等,而且也影响着不孕症患者的妊娠结局。本文将从GDF-8对卵泡发育、排卵、胎盘功能调控以及在生殖疾病调控和辅助生殖技术应用中的作用等方面进行综述,以期为相关疾病的临床诊断和治疗提出新的思路和方法。

2型糖尿病肾病患者生长分化因子-15的表达及临床意义

目的：探讨生长分化因子-15（GDF-15）在2型糖尿病肾病中的表达水平及其临床意义。方法纳入80例2型糖尿病（T2DM）患者，根据Mogensen分期标准，分为正常白蛋白尿组（30例）、微量白蛋白尿组（20例）和大量白蛋白尿组（30例），采用ELISA法测定血浆GDF-15水平。结果大量白蛋白尿组GDF-15水平高于微量白蛋白尿组和正常白蛋白尿组（P均＆lt;0.01），分别为1773.9（1099.1-2357.4）pg/ml、864.0（636.1-994.3）pg/ml和704.5（548.8-975.8）pg/ml；微量白蛋白尿组GDF-15水平高于正常白蛋白尿组（P＆gt;0.05），且在肾功能轻度受损（60≤肾小球滤过率＆lt;90 ml/min/1.73 m2）时GDF-15浓度即有增加，为999.5（769.2-1372.1）pg/ml。偏相关分析显示，血浆GDF-15与糖尿病病程、尿微量白蛋白（mAlb）、尿素氮（BUN）及肌酐（sCr）呈正相关（r=0.246，0.493，0.390，0.471，P均＆lt;0.05），与估计的肾小球滤过率（eGFR）及血浆白蛋白（Alb）呈负相关（r=-0.438，-0.397，P均＆lt;0.01）。多元线性回归分析提示较高水平的GDF-15为mAlb增加的独立危险因素。在对肾功能受损（eGFR＆lt;90 ml/min/1.73 m2）的诊断中，GDF-15和mAlb的曲线下面积分别为0.801和0.717，GDF-15曲线下面积大于mAlb（P＆lt;0.05）。当733.78 pg/ml作为GDF-15诊断肾功能受损的临界值时，敏感性和特异性达到最佳，分别为88.1%和58.1%。结论GDF-15在2型糖尿病肾病不同临床阶段有不同程度的增高，不但与mAlb、eGFR有良好的相关性，而且是mAlb增加的独立危险因素，故在2型糖尿病肾病的早期诊断、病情评估及预测其疾病转归方面具有一定的应用价值。

人血清生长分化因子15与冠心病患者慢性心力衰竭的相关性研究

目的 探讨生长分化因子15（GDF-15）与冠心病患者慢性心力衰竭的关系及诊断价值.方法 选择复旦大学附属华山医院心内科269例行冠状动脉造影（CAG）检查的患者,根据CAG、心电图及心肌酶学检查结果分为3组：其中冠心病心肌梗死患者98例（MI组）,本组再根据纽约心脏病协会（NYHA）心功能分级Ⅰ～Ⅳ级分为4个亚组;未经历心肌梗死的冠心病患者84例（CAD组）;CAG正常患者87例（对照组）.采用酶联免疫吸附法测定患者GDF-15浓度.分析GDF-15与NYHA分级和血清N末端脑钠肽原（NT-proBNP）的关系.结果 MI组平均及其各不同心功能分级亚组[纽约心脏病协会（NYHA）Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级]、CAD组血清GDF-15浓度明显高于对照组,差异有统计学意义[1 622（888,1 995）,983 （808,1 501）、1 614（810,1 825）、1 940（1 837,2 063）、3 905（3 690,4 019）,945（856,1 000） ng/L比798 （728,873） ng/L] （P ＜0.05）.MI组平均及其各不同心功能分级亚组（NYHA Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级）血清NT-proBNP浓度明显高于对照组,差异有统计学意义[564（158,857）,233（105,552）、278（133,716）、790（636,1 490）、4 665（3 712,5 442） ng/L比121（108,134）ng/L] （P ＜0.05）.相关性分析显示GDF-15水平与血清NT-proBNP水平呈显著正相关（r=0.861,P＜0.01）,与血清LVEF呈显著负相关（r=-0.936,P＜0.01）.GDF-15与NT-proBNP对慢性心力衰竭的受试者工作特征曲线结果显示其下面积分别为0.804、0.795（P ＜0.01）.GDF-15的最佳临界值为1 086.38 ng/L时,对慢性心力衰竭诊断的敏感性为72.4％,特异性为93.6％.结论 GDF-15是一个新的冠心病患者慢性心力衰竭预后诊断标志物,能够对心力衰竭的严重程度进行客观评价.