氨基胍对糖尿病大鼠肾组织中内皮素及其受体基因表达的作用

The effect of aminoguanidine on gene expression of endothelins and their receptors in diabetic kidney tissue

目的探讨非酶糖化作用对糖尿病大鼠肾组织中内皮素及其受体基因表达的影响。方法采用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）技术，观察糖尿病大鼠肾皮质中内皮素及其受体基因表达的变化，以及氨基胍对其表达的影响。结果诱发糖尿病８周的大鼠肾皮质内ＥＴ－１及ＥＴ－Ａ受体的基因表达明显增加，ＥＴ－３ｍＲＮＡ水平与正常相比未见明显改变，但ＥＴ－Ｂ受体ｍＲＮＡ表达下降。氨基胍给药使糖尿病大鼠肾皮质内增加的ＥＴ－１及ＥＴ－Ａ受体ｍＲ－ＮＡ水平明显降低，同时使ＥＴ－３及ＥＴ－Ｂ受体ｍＲＮＡ表达明显增加。结论糖尿病状态下，ＥＴ－１、ＥＴ－３可能以不同的方式参与肾脏结构和功能的改变；氨基胍治疗能有效地调节糖尿病肾组织内异常的ＥＴ及其受体的基因表达，缓解肾脏损害。

Objective To investigate aminoguanidine effects on ETs and their receptors in the kidney of diabetic rats Methods Four groups of rats,control rats with and without aminoguanidine (AG) treatment,diabetic rats without aminoguanidine and diabetic rats who received aminoguanidine were followed up for 8wk with 4 weekly measurements of urinary albumin excretion by means of RIARTPCR were used to measure the amount of ETs and their receptors mRNAs expression Results 8wk after the onset of diabetes,ET1 and ET receptor A(ETAR) mRNA levels increased significantly in diabetic renal cortex. In contrast,ET3 mRNA level was not altered in renal cortex from diabetic and control rats and ETAR mRNA level was declined in diabetic renal cortex.Aminoguanidine treatment partly ameliorated the increase in mRNA for EFI in renal cortex of diabetic rats, while,made elevated ETAR mRNA level observed in diabetic cortex lower to normal level. On the other hand,AG administration enhanced ET3 gene cxpression in diabetes beyond the levels in normal rats as well as upregulated ETARmRNA expression in diabetes rats reaching the levels observed in control ratsConclusion ET1 and ET3 may affect kidney function in different ways,that enhanced renal endothelin may favor the development of renal lesions related with diabetesAminoguanidine therapy may be effective in regulate abnormal ETs and ET receptors gene expression in the renal cortex of diabetic nephropathy,raising the possibility that AGEs formed in renal cortex may affect ETs and ET receptors gene expressions which contributes to the regulation of renal hemodynamics and glomerular ECM proliferation associated with diabetes