ET-1mRNA反义寡核苷酸治疗模式下糖尿病大鼠生存状况及肾脏病理进展研究

Study on the survival status and renal pathological progress of diabetic rats under ET-1 mrna antisense oligonucleotide therapy

目的对糖尿病肾病(DN)大鼠模型利用内皮素反义寡核苷酸(ET-1AS-ODN)技术进行干预治疗,探讨ET-1AS-ODN在糖尿病肾病(DN)早期肾功能的保护作用。方法使用64只健康的SD雄性大鼠,通过腹腔注射链尿佐菌素(STZ)以剂量为55~60 mg/kg的方法制备糖尿病模型。随后,对其中32只大鼠给予ET-1AS-ODN 6 OD/kg/wk的治疗。在治疗过程中,对大鼠的生存状况及肾功能病理进展情况进行动态观察和测量。结果经过2、4、6、8周实验动物饲养后,与生理盐水对照组相比,8周后模型组(DM)生存率极低(P<0.05),肾功能检测血肌酐(Scr)、尿肌酐、尿素氮(BUN)水平、ET-1含量显著增高。ET-1AS-ODN治疗组在8周后效果显著,能够明显降低DN大鼠的血肌酐(Scr)和尿素氮(BUN)水平,并提高肌酐清除率(Ccr),其差异有统计学意义(P<0.05)。结论经AS-ODN早期干预治疗可以有效改善糖尿病大鼠的生存状态,并对肾功能具有保护作用。

Objective To investigate the protective effect and mechanism of endothelin antisense oligodeoxynucleotide(ET-1As-ODN)in the early renal function of diabetic nephropathy(DN)by using endothelin antisense oligonucleotide(ET-1AS-ODN).Methods 64 healthy SD male rats were selected to prepare diabetic models by intrabitoneal injection of streptozotocin(STZ)at 60 mg/kg,and 32 of them were treated with endothelin antisense oligonucleotide(ET-1AS-ODN)at 6 OD/kg/wk.The survival status and pathological progression of renal function in rats were dynamically observed and measured.Results Compared with the normal group,the survival rate of the model group(DM)was very low after 8 weeks(P<0.05),and the content of creatinine(Scr),urinary creatinine,urea nitrogen(BUN)and ET-1 in the blood were significantly increased.After 8 weeks of treatment with ET-1mRNA antisense oligonucleotide,the level of BUN and Scr significantly reduced and the level of Ccr increased in the rats of ET-1AS-ODN group(P<0.05).Conclusion The early intervention of AS-ODN can effectively improve the survival status of diabetes rats and protect renal function.