成纤维细胞生长因子1及其突变体对2型糖尿病小鼠血糖的影响  

The effects of fibroblast growth factor 1 and its mutant on blood glucose in type 2 diabetic mice

作　　者：金辉[1] 王陈翔[1] 梁晶[1] Jin Hui;Wang Chenxiang;Liang Jing(Department of Pharmacy of the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第一医院药学部,325000

出　　处：《中华糖尿病杂志》2020年第6期409-414,共6页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：温州市公益性社会发展(医疗卫生)科技项目(Y20160162)。

摘　　要：目的研究成纤维细胞生长因子1(FGF1)及其突变体(FGF1^ΔHBS)对链脲佐菌素(STZ)诱导的2型糖尿病小鼠血糖的影响。方法利用STZ建立2型糖尿病小鼠模型,完全随机法分为模型组、FGF1给药组、FGF1^ΔHBS给药组(低、中、高剂量)和正常对照组,模型组和正常对照组给予等量的生理盐水。急性作用研究采用单次腹腔注射方式给药(FGF1给药组按0.5 mg/kg给予单次腹腔注射,FGF1^ΔHBS按低、中、高三种剂量给予单次腹腔注射),慢性作用研究采用腹腔注射方式隔天给药(进行完急性作用研究后,各组小鼠按上述剂量继续隔天腹腔注射),连续28 d,观察记录小鼠生活状态,监测血糖变化情况。观察FGF1及其突变体对小鼠血清胰岛素和肝糖原含量的影响。通过小鼠胚胎成纤维细胞实验考察比较FGF1与FGF1^ΔHBS促细胞增殖作用。多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验。结果模型组小鼠比正常组体重、血糖、血清胰岛素和肝糖原含量明显增加(t=9.347、20.321、12.723、4.545,均P<0.05)。与模型组相比,FGF1及FGF1^ΔHBS(低、中、高剂量)给药组小鼠血糖明显下降(t=15.650、15.513、16.261、16.929,均P<0.05),且单次作用可持续24 h,血清胰岛素明显下降[(0.41±0.14)、(0.46±0.06)、(0.4±0.06)、(0.37±0.06)比(0.90±0.12)ng/ml,t=10.509、9.282、10.616、11.256,均P<0.05],肝糖原含量进一步增加[(24.38±6.8)、(26.5±3.43)、(27.2±3.15)、(28.45±2.23)比(15.16±3.66)mg/g,t=3.372、6.391、7.049、8.762,均P<0.05]。FGF1^ΔHBS低、中、高各剂量组差异无统计学意义(均P>0.05)。FGF1^ΔHBS的吸光度较FGF1下降,显示促细胞增殖作用明显下降(0.42±0.01比0.65±0.04,t=14.067,P<0.05)。结论FGF1^ΔHBS基本丧失了促细胞分裂能力,但其降血糖作用与FGF1基本相似,机制可能是通过改变胰岛素敏感性来增加肝糖原含量,具有进一步开发成为治疗糖尿病药物的潜力。Objective To study the effects of fibroblast growth factor 1(FGF1)and its mutant(FGF1^ΔHBS)on blood glucose of type 2 diabetic mice induced by streptozotocin.Methods The model of type 2 diabetic mice was established using streptozotocin(STZ).Mice were randomly divided into model group,FGF1 treatment group,FGF1^ΔHBS treatment group(low,medium and high dose)and control group.The model group and control group were given the same amount of saline.The acute effect study was given by single intraperitoneal injection(the FGF1 group was given a single intraperitoneal injection at 0.5 mg/kg,and FGF1^ΔHBS was given a single intraperitoneal injection at low,medium,and high does),while the chronic effect study was given by intraperitoneal injection every other day for 28 consecutive days(after the acute effect study,mice in each group were injected intraperitoneally at the above dose the next day).Observe and record the living conditions of mice,monitored the blood glucose changes of mice.Observe the effect of FGF1 and its mutants on the changes of serum insulin and liver glycogen in mice.Comparison of the proliferation effects of FGF1 and FGF1^ΔHBS on the mice embryonic fibroblasts.One-way analysis of variance was used for comparison between groups,and LSD-t test was used for pantwise comparison between groups.Results Compared with the normal group,the body weight,blood glucose,serum insulin and liver glycogen content increased significantly(t=9.347,20.321,12.723,4.545,all P<0.05).Compared with the model group,the blood glucose of FGF1 and FGF1^ΔHBS treatment group(low,medium and high doses)was decreased significantly(t=15.650,15.513,16.261,16.929,all P<0.05),and the single effect lasted for 24 hours.Serum insulin[(0.41±0.14),(0.46±0.06),(0.40±0.06)and(0.37±0.06)vs(0.90±0.12)ng/ml,t=10.509,9.282,10.616,11.256,all P<0.05]decreased significantly,and the liver glycogen content[(24.38±6.8),(26.5±3.43),(27.2±3.15)and(28.45±2.23)vs(15.16±3.66)mg/g,t=3.372,6.391,7.049,8.762,all P<0.05]increased further.There was no

关 键 词：糖尿病 2型 成纤维细胞生长因子1 突变体 

分 类 号：R587.1[医药卫生—内分泌]