氨基胍对糖尿病大鼠肾组织中糖化终产物受体mRNA表达的调节

Effect of aminoguanidine on mRNA expression of specific receptor of the advanced glycation end products in diabetic kidney tissue in rats

目的研究氨基胍对糖尿病肾组织内糖化终产物（ＡＧＥｓ）受体（ＲＡＧＥ）ｍＲＮＡ表达的影响。方法采用逆转录聚合酶链式反应（ＲＴＰＣＲ）检测病程８周肾内ＲＡＧＥｍＲＮＡ水平。结果诱发糖尿病４周后糖尿病大鼠肾皮、髓质内ＲＡＧＥｍＲＮＡ表达增加（Ｐ＜０．０５），８周时更为明显（Ｐ＜０．０５）；口服补充氨基胍４周对肾内这种改变未产生影响（Ｐ＞０．０５），给药８周，糖尿病大鼠肾皮、髓质内增强的ＲＡＧＥｍＲＮＡ表达明显缓解（Ｐ＜０．０５）。与此同时，氨基胍在不影响血糖的基础上，使糖尿病大鼠升高的糖化血红蛋白（ＧＨｂ）水平下降２６．７２％。结论糖尿病状态下，肾组织内ＲＡＧＥｍＲＮＡ高表达可能是高血糖诱发ＡＧＥｓ形成的结果；氨基胍可通过调节ＲＡＧＥｍＲＮＡ的异常表达，缓解ＡＧＥｓ对肾组织的损伤。

Objective Investigatingtheeffectofaminoguanidine (AG) on RAGE (receptor for advanced glycation end products) mRNA expression in renal tissue of streptozotocin (STZ) induced diabetic rats. Methods Four groups of rats, including (1)control rats without AG; (2)control rats with AG; (3)diabetic rats without AG and (4)diabetic rats receiving AG, were observed for 8 weeks, with the measurements of RAGE mRNA expression every 4 weeks by quantitative reverse transcription polymerase chain reaction (RT PCR). Results After 4 weeks of diabetes inducement,RAGEmRNAlevelsshoweda continuous increase until 8th week, in both diabetic renal cortex and medulla (P<0.05, diabetes vs control). The RAGE mRNA levels in renal cortex and medulla of control rats did not change significantly with age. AG, as the prototype inhibitor of AGEs formation, when administered to diabetic rats for 4 weeks, did not haveanyvisibleeffecton the alterations of renal RAGE mRNA in diabetes. By continuous administration up to 8th week, thosealterationsof RAGE mRNA both in diabetic renal cortex and medulla were all attenuated (P<0.05, diabetes with AG vs diabetes without AG). Similarly, after 8 weeks, diabetic rats had a significantly higher GHb level (diabetes vs control: 7.71%±0.22% vs 2.95%±0.52%, P<0.001). AG treatment for 8 weeks lowered GHb levels by 26.72% (P<0.05). Conclusion The excessive gene expression of RAGE in renal tissue of diabetic rats might occur as a result of hyperglycemia induced AGEs formation and the decrease of AGEs level by AG therapy attenuated the abnormal RAGE gene expression pattern which could contribute to preventing renal damage from AGEs accumulation.