2型糖尿病相关静脉桥内膜增生的动物模型建立与机制分析

Establishment of an animal model and mechanism analysis of type 2 diabetes-related venous bridging intimal hyperplasia

目的探讨2型糖尿病(T2DM)相关静脉桥内膜增生的建模方法,并初步分析T2DM导致静脉桥病变的机制。方法2019年9—11月于北京安贞医院动物实验室进行实验。36只新西兰雄性大白兔随机数字表法分为T2DM组(n=24)和对照组(n=12)。T2DM组用链脲佐菌素50 mg/kg,于第1、3、6 d给药3次,诱发T2DM。2组均用血管吻合轮法建立兔颈动脉旁路移植模型。饲养4周后病理观察2组颈静脉桥病变,以及IL-6和VCAM-1的表达。结果T2DM组18只和对照组12只成功存活4周。与对照组比较,T2DM组静脉桥炎性细胞浸润明显增多,内膜显著增厚[(137.8±19.2)μm vs.(116.2±15.5)μm,t=3.249,P<0.01)];T2DM组静脉桥中IL-6和VCAM-1的蛋白质表达显著增多(IL-6:12.5±2.2 vs.7.8±1.4,t=6.549,P<0.01;VCAM-1:48.3±7.9 vs.22.1±5.6,t=9.921,P<0.01)。结论链脲佐菌素诱发T2DM联合血管吻合轮法颈动脉旁路移植是一种建立T2DM相关静脉桥内膜增生兔模型的可靠方法,T2DM可通过调控致炎性细胞因子表达影响静脉桥病变。

Objective To explore the modeling method of type 2 diabetes(T2DM)-related venous bridge intimal hyperplasia,and to analyze the mechanism of T2DM leading to venous bridge disease.Methods Thirty-six New Zealand male white rabbits were randomly divided into T2DM group(n=24)and control group(n=12).In the T2DM group,50 mg/kg of streptozotocin was administered 3 times on the 1st,3rd,and 6th day to induce T2DM.In both groups,the rabbit carotid artery bypass graft model was established by vascular anastomosis round method.After 4 weeks of rearing,pathological observation of the jugular vein bridge lesions and the expression of IL-6 and VCAM-1 in the 2 groups were observed.Results 18 rats in the T2DM group and 12 rats in the control group survived for 4 weeks.Compared with the control group,the venous bridge inflammatory cell infiltration in the T2DM group was significantly increased,and the intima was significantly thickened[(137.8±19.2)μm vs.(116.2±15.5)μm,t=3.249,P<0.01)];the vein of the T2DM group The protein expression of IL-6 and VCAM-1 in the bridge increased significantly(IL-6:12.5±2.2 vs.7.8±1.4,t=6.549,P<0.01;VCAM-1:48.3±7.9 vs.22.1±5.6,t=9.921,P<0.01).Conclusion Streptozotocin-induced T2DM combined with vascular anastomosis round carotid artery bypass grafting is a reliable method to establish a rabbit model of T2DM-related venous bridging intimal hyperplasia.T2DM can affect venous bridging disease by regulating the expression of inflammatory cytokines.