不同生长激素-胰岛素样生长因子1轴功能状态下患者体内成纤维生长因子21的变化及其与糖脂代谢的关系

Variations of serum fibroblast growth factor 21 in patients with GH-IGF1 axis dysfunctions and its relations with glucolipid metabolism

目的探讨不同生长激素-胰岛素样生长因子1(GH-IGF1)轴功能状态下血清成纤维生长因子21(FGF21)水平及其与糖脂代谢的关系。方法纳入2015年1月至2016年5月在首都医科大学附属北京天坛医院内分泌科住院治疗的肢端肥大症患者35例作为GH-IGF1轴功能亢进组,鞍区疾病(如颅咽管瘤、垂体无功能大腺瘤术后,炎症,外伤等)GH-IGF1功能减低患者32例作为GH-IGF-1轴功能低下组,同期来院行健康体检的健康者30例作为对照组,采用双抗夹心酶联免疫吸附(ELISA)法检测所有受试者血清FGF21的表达,比较三组之间身高、体质量、体质量指数(BMI)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FPG)、糖化血红蛋白(Hb A1c)水平;并分析血清FGF21水平与糖代谢及脂代谢的相关性。结果 FGF21:GH-IGF1功能亢进组(606,898)μg·L-1低于GH-IGF1功能低下组(25.0,64.5)μg·L-1,差异有统计学意义(P<0.05),而与对照组(158.75,233.25)μg·L-1比较,均差异无统计学意义(P>0.05)。TG:GH-IGF1功能亢进组(1.14,2.20)mmol·L-1及GH-IGF1功能低下组(1.22,3.13)mmol·L-1均高于对照组(0.74,1.20)mmol·L-1,且差异有统计学意义(P<0.05)。HDL:GH-IGF1功能亢进组(1.19±0.26)mmol·L-1及GHIGF1功能低下组(1.14±0.44)mmol·L-1均低于对照组(1.63±0.64)mmol·L-1。TC:GH-IGF1功能低下组(4.85±1.25)mmol·L-1高于对照组(4.30±0.53)mmol·L-1;GH-IGF1功能亢进组FPG、Hb A1c高于其他两组;均差异有统计学意义(P<0.05);相关性分析显示,FGF21与GH、IGF-1呈负相关,而与TG、TC呈正相关。结论 FGF21在GH-IGF1轴功能低下组表达水平大于GH-IGF1轴功能亢进组,可能与其他因素共同介导了GH-IGF1轴的生长发育与物质代谢的过程,为临床探索GHIGF1轴功能异常所致疾病的机制及治疗提供了新的思路。

Objective Abstract： Objective To investigate the concentration of serum fibroblast growth factor 21（FGF21） in patients with GH-IGF1 axis dysfunction and its relationship with glucolipid metabolism. Methods 35 inpatient cases of acromegaly treated at the Department of Endocrinology of Beijing Tiantan Hospital affiliated to Capital Medical University from January 2015 to May 2016 were enrolled into the GH-IGF1 axis hyperfunction group,32 inpatient cases of saddle area disease（such as craniopharyngioma,large pituitary non-functional adenomas,postoperative inflammation,and trauma） into the GH-IGF1 axis hypofunction group and 30 cases of healthy subjects who came to our hospital for health examination during the above-mentioned period were enrolled as the control group.The serum FGF21 expression of all the subjects were tested using the double antibody sandwich ELISA method The three groups were compared in terms of their heigh,weight and body mass index（BMI）,total cholesterol（TC）,triglyceride（TG）,low density lipoprotein cholesterol（LDL-C）,high density lipoprotein cholesterol（HDL-C）,fasting blood glucose（FPG）,and glycosylated hemoglobin（Hb A1 c）. Also the correlation between the serum FGF21 concentrations and the glucose-lipid metabolism was analyzed. Results The concentration of serum FGF 21 of the hyperfunction group（606,898） μg·L^-1 was lower than that of the hypofunction group（25,64. 5） μg·L^-1,with the difference being statistically significant（P〈0. 05）. Compared with the control group（158. 75,233. 25） μg·L^-1,there was no statistically significant（P〉0. 05）. The TG of both GH-IGF1 hyperfunction group（1. 14,2. 20） mmol·L^-1 and GH-IGF1 hypofunction group（1. 22,3. 13） mmol·L^-1 was higher than the control group（0. 74,1. 20） mmol·L^-1,while the HDL lower than the control group,which were statistically significant（P〈0. 05）. The TC of the GH-IGF1 hypofunction group（4. 85 ± 1. 25）mmol·L^-1 was higher than the control group（4. 30 ± 0. 53） mmol·L^-1. The FPG and Hb A1 c of the GH-IGF1 hyperfunction groupwere higher than the other two groups; their differences were both statistically significant（P〈0. 05）. A correlation analysis found that FGF21 was negatively correlated to GH and IGF-1,and positively correlated to TG and TC. Conclusion The expression of FGF21 in GH-IGF1 axis hypofunction group was higher than GH-IGF1 hyperfunction group,which may mediate the growth and metabolism of GH-IGF1 axis together with other factors. And providing a new way for exploring the mechanism and treatment of GH-IGF1 axis dysfunction.