摘要
目的探讨糖尿病前期到2型糖尿病(T2DM)发展阶段中,DOK1基因在小鼠多个组织里的表达差异,以及其与血脂水平间的相关性。方法将小鼠分为0 d组(对照)、20 d组、40 d组、60 d组、80 d组及糖尿病组(T2DM)。0 d组喂普通饲料,其余4组喂高脂饲料建立糖尿病前期模型,T2DM组在此基础上以链脲佐菌素(STZ)低剂量多次腹腔注射建立T2DM模型。测定各组小鼠的空腹、腹腔注射葡萄糖耐量实验(IPGTT)和胰岛素耐量实验(IPITT)血糖,并使用qPCR技术检测9种组织(心脏、肝脏、肾脏、骨骼肌、胰腺、脂肪、脾脏、肺和结肠组织)中DOK1基因的表达情况。ELISA方法测定血清中的DOK1水平,并利用全自动生化分析仪测定血清中的血脂水平。通过Spearman相关性分析80 d及T2DM组小鼠血清DOK1与TG、TC、HDL-C、LDL-C、脂蛋白A[LP(a)]和游离脂肪酸(FFA)的相关性。结果成功建立了糖尿病前期和T2DM模型小鼠;与0 d组比较,80 d组、T2DM组的空腹、IPGTT、IPITT血糖和血脂水平明显升高(P<0.001);与0 d组比较,T2DM组心脏、肝脏、肾脏、骨骼肌、胰腺和脂肪组织DOK1 mRNA表达水平均明显下降(P<0.05);与0 d组比较,80 d组心脏、肝脏、肾脏和骨骼肌DOK1 mRNA表达水平均明显下降(P<0.05);与0 d组比较,40 d组与60 d组肝脏组织DOK1 mRNA表达水平明显下降(P<0.05);与0 d组比较,各组脾脏、肺及结肠组织中DOK1 mRNA表达水平差异均无统计学意义(P>0.05)。80 d和T2DM组小鼠血清DOK1与TG、TC、LDL-C、LP(a)、FFA呈负相关关系(r=-0.7878、-0.7272、-0.7637、-0.7642、-0.8925,P<0.001),与HDL-C呈正相关关系(r=0.9613,P<0.001)。结论DOK1的降低与胰岛素抵抗的机制有关,并有可能在与糖尿病有关的脂质代谢失调中起到关键作用。
Objective To explore the expression differences of the docking protein 1(DOK1)gene in multiple tissues of mice during the development stage from prediabetes to type 2 diabetes mellitus(T2DM),as well as its correlation with blood lipid levels.Methods The mice were divided into the 0 d group(control),the 20 d group,the 40 d group,the 60 d group,the 80 d group and the T2DM group.The 0 d group was fed with normal diet,while the other four groups were fed with high-fat diet to establish the prediabetes model.On this basis,the T2DM group was given low-dose multiple intraperitoneal injections of streptozotocin(STZ)to establish the T2DM model.The fasting and intraperitoneal glucose tolerance test(IPGTT)and insulin tolerance test(IPITT)blood glucose of mice in each group were detected,and the expression of the DOK1 gene in nine tissues(heart,liver,kidney,skeletal muscle,pancreas,adipose,spleen,lung and colon tissues)was detected by qPCR.The level of DOK1 in serum was determined by ELISA,and the lipid level in serum was measured by an automatic biochemical analyzer.The correlations between serum DOK1 and TG,TC,HDL-C,LDL-C,lipoprotein A[LP(a)],and free fatty acids(FFA)were analyzed by Spearman correlation analysis.Results The prediabetic and T2DM model mice were successfully established.Compared with the 0 d group,the blood glucose and lipid levels in the 80 d group and the T2DM group were significantly increased(P<0.001).Compared with the 0 d group,the expression level of DOK1 mRNA in the T2DM group was significantly decreased in heart,liver,kidney,skeletal muscle,pancreas and adipose tissue(P<0.05).Compared with the 0 d group,the expression level of DOK1 mRNA in the 80 d group was significantly decreased in heart,liver,kidney and skeletal muscle tissue(P<0.05).Compared with the 0 d group,the expression levels of DOK1 mRNA in the 40 d group and the 60 d group was significantly decreased in the liver tissues(P<0.05).Compared with group 0 d,there was no statistically significant difference in the expression level of DOK1 mRNA in the spleen,lung and colon tissues among each group(P>0.05).DOK1 in the 80 d group and the T2DM group was negatively correlated with TG,TC,LDL-C,LP(a),and FFA(r=-0.7878,-0.7272,-0.7637,-0.7642,-0.8925,P<0.001),while positively correlated with HDL-C(r=0.9613,P<0.001).Conclusion The reduction of DOK is related to the mechanism of insulin resistance and may play a key role in lipid metabolism disorders associated with diabetes.
作者
蔡小玲
王海燕
苏占海
哈小琴
CAI Xiaoling;WANG Haiyan;SU Zhanhai;HA Xiaoqin(Department of Medical Laboratory,Qinghai Provincial People’s Hospital,Xining,Qinghai 810000,China;College of Clinical Medicine,Qinghai University,Xining,Qinghai 810001,China;Department of Medical Laboratory,the 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army,Lanzhou,Gansu 710050,China)
出处
《重庆医学》
2025年第8期1781-1786,共6页
Chongqing Medical Journal
基金
青海省创新平台建设专项项目(2018-SF-L3)。
