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目的构建大鼠DN模型,探讨外源性予腺病毒(Ang-1)对肾脏的血管生成标志物血栓调节蛋白-1(TM-1)和Ki-67的影响及肾新生血管生成方面的作用。方法将糖尿病大鼠分为Ang-1腺病毒组、空白载体组和DM模型组。Ang-1腺病毒组造模完成后8周,单次注射Ang-1腺病毒,剂量0.05ml/只;空白载体组单次注射Ang-1腺病毒的载体;DM模型组单次注射同剂量的0.9%生理盐水。另有正常对照组(NC),单次注射同剂量的0.9%生理盐水。注射后8、12、20和28周,分别对各组24h尿蛋白定量、肾组织的TM-1和Ki-67进行检测。结果 Ang-1腺病毒组、空白载体组和DM模型组24h尿蛋白表达较NC组升高(P<0.05),肾小球组织中TM-1和Ki-67表达较NC组增强(P<0.05),20周达峰值,各时点Ang-1腺病毒组的TM-1和Ki-67均强于同时点空白载体组和DM模型组(P<0.05)。24h尿蛋白与糖尿病大鼠肾组织的TM-1和Ki-67表达均呈正相关(P<0.05)。结论糖尿病大鼠的肾小球组织有新生血管生成,Ang-1具有促进糖尿病大鼠的肾小球组织有新生血管生成作用,TM-1和Ki-67可能参与其中。
Objective To construct rat model of DN and investigate the effects of exogenous adenovirus (Ad-1) on renal angiogenesis markers thrombomodulin-1 (TM-1) and Ki-67 and renal neovascularization . Methods Diabetic rats were divided into Ang-1 adenovirus group, blank vector group and DM model group. The Ang-1 adenovirus group was injected with Ang-1 adenovirus at a dose of 0.05ml / week for 8 weeks after the model was established. A single injection of Ang-1 adenovirus vector was used in the blank vector group. Of 0.9% saline. Another normal control group (NC), a single injection of the same dose of 0.9% saline. At 8, 12, 20 and 28 weeks after injection, 24-hour urinary protein and TM-1 and Ki-67 in renal tissue were detected respectively. Results The expressions of 24 h urinary protein in Ang-1 adenovirus group, blank vector group and DM model group were higher than those in NC group (P <0.05), and the expression of TM-1 and Ki-67 in glomerular tissue were significantly increased compared with NC group (P < 0.05) and peaked at 20 weeks. TM-1 and Ki-67 of Ang-1 adenovirus group were higher than those of blank vector group and DM model group at each time point (P <0.05). 24h urine protein and the expression of TM-1 and Ki-67 in kidney tissue of diabetic rats were positively correlated (P <0.05). Conclusion Glomerular neovascularization is induced in diabetic rats. Ang-1 can promote glomerular neovascularization in diabetic rats, and TM-1 and Ki-67 may participate in it.