高血糖状态对缺血后血管新生影响的机制研究

目的探讨链脲佐菌素(STZ)诱导的高血糖状态对大鼠单侧下肢缺血后血管新生影响的作用机制。方法糖尿病组(n=18)采用柠檬酸钠缓冲液稀释STZ,70 mg/kg一次性腹腔注射制作糖尿病模型;正常对照组大鼠(n=18)给予等量柠檬酸钠缓冲液一次性腹腔注射。均手术结扎切除左侧股动、静脉造成单侧下肢缺血。分别于手术当天和第7天检测尾静脉血糖;第15天两组各处死9只大鼠检测血清血糖、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、总抗氧化能力(TAOC)、黄嘌呤氧化酶(XOD)、肌肉组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)和环磷酸鸟苷(cGMP)含量,碱性磷酸酶染色法测定缺血区域肌肉毛细血管密度;两组剩余各9只大鼠血管造影法观察双下肢血管生成情况。结果术后15 d,毛细血管缺血区域毛细血管评分记数和毛细血管密度均表明糖尿病组明显低于正常对照组(P<0.05),与血清中血糖、HDL及组织中的SOD、XOD、NO和cGMP含量变化相关。结论STZ诱导的高血糖状态对缺血后血管新生有明显的抑制作用,可能与糖脂代谢紊乱、氧化应激状态及内皮功能受损有关。

Mechanism of effect of hyperglycemia on angiogenesis after ischemia

Objective To explore the mechanism of effect of streptozotocin(STZ)-induced hyperglycemia on angiogenesis in the ischemic hindlimb of diabetic rats. Methods For the diabetes group(n=18),STZ was diluted by sodium citrate buffer and was administed to the rats by intraperitoneal injection at 70 mg/kg to establish the diabetes model.Those in the normal control group(n=18)were intraperitoneally injected with sodium citrate buffer.Unilateral hindlimb ischemia was established by excising the left femoral artery and vein.The blood glucose of vena caudalis was measured at the day of operation and the seventh day.Nine rats in each group were sacrificed at the fifteenth day for the detection of serum glucose,total cholesterol(TC),triglyeride(TG),low-density lipoprotein(LDL),high-density lipoprotein(HDL),total anti-oxygen capability(TAOC),xanthine oxidase(XOD),muscle tissue superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO) and cyclic guanosine monophosphate(cGMP).Muscule capillary vessel density of ischemic region was measured by alkaline phosphatase staining methods.The angiogenesis of both hindlimbs of the other 9 rats in each group was observed by angiography. Results Fifteen days after operation,angiographic score and capillary vessel density of ischemic region were significantly lower in diabetes group than in control group(P<0.05),and the differences were associated with the changes in blood glucose,HDL,tissue SOD,XOD,NO and cGMP. Conclusion Angiogenesis after ischemia can be significantly inhibited by STZ-induced hyperglycemia,which may be correlated with glucose and lipid metabolism disorder,oxidative stress and endothelial function injury.