Construction of type 2 diabetes rat models of lower limb ischemia by feeding with high-fat diet / 中国组织工程研究

ABSTRACT

BACKGROUND:The method of ligating or resecting rat lower limb femoral or iliac artery has been widely used to make rat models of lower limb ischemia, but there have been no stable and efective methods used to establish diabetic models of chronic atherosclerotic occlusive diseases and to evaluate the ischemic status of hindlimbs of models. OBJECTIVE: To establish type 2 diabetes rat models of lower limb ischemia by feeding with high-fat diet and to evaluate them. METHODS:Twenty rats were randomly and evenly divided into diabetes group (n=10) and control group (n=10). Rats in the diabetes group were fed with high-fat diet for 6 months, and were intraperitonealy injected with streptozotocin (50 mg/kg) to induce diabetes. Rats in the control group were fed with normal diet for 6 months. Rats in these two groups were subjected to ligation of femoral artery to establish right lower limb ischemia models. RESULTS AND CONCLUSION:At the first day of modeling, color Doppler flow imaging and CT angiography showed obviously decreased blood flow suggesting the success of establishing ischemia model. At 7 and14 days after modeling, the blood flow of rats in these two groups showed a gradual recovery as detected by color Doppler flow imaging. At 28 days after modeling, blood flow of rats in the diabetes group was significantly slower than that in the control group (P < 0.05). CT angiography showed that at 28 days after modeling, only a smal amount of compensatory increase in blood flow of the blood vessels at the ligation position of proximal right lower limb femoral artery was seen in the diabetes group, while no obvious blow was observed in the distal part. Histopathologic and immunohistochemical staining showed that at 28 days after modeling, destroyed tissue structure and inflammatory cel infiltration were observed in the ischemic region and capilary density on the affected side was lower than that on the healthy side. The protein expression of vascular endothelial growth factor in the ischemic muscle tissue of rats in the diabetes group was significantly increased compared with that in the control group (P < 0.05). These results show that diabetic rat models of lower limb ischemia can be successfuly established by long term high-fat diet feeding and femoral artery ligation and they can be validated by CT angiography.