莫诺苷对晚期糖基化终末产物加重链脲佐菌素诱导糖尿病肾病保护作用及其机制

Protection of morroniside on STZ-induded diabetic nephropathy aggravated by AGEs in mice and its mechanism

目的探讨山茱萸Cornus officinalis中效应成分莫诺苷对晚期糖基化终末产物(AGEs)加重链脲佐菌素(STZ)诱导糖尿病肾病(DN)小鼠的保护机制。方法将STZ诱导成功的DN小鼠饲喂高AGEs饲料,并分别ig给予氨基胍(0.1 g/kg)、二甲双胍(0.2 g/kg)、卡托普利(0.02 g/kg)、莫诺苷低剂量(0.02 g/kg)和莫诺苷高剂量(0.10 g/kg)12周。检测空腹血糖、胰岛素、血清肌酐和尿素氮、血清和肾脏AGEs、24 h尿蛋白等指标,RT-PCR法检测肾组织中晚期糖基化终末产物受体(RAGE)m RNA表达,Westorn blotting法检测肾组织中RAGE蛋白表达,观察各组小鼠胰腺和肾脏的病理改变。结果莫诺苷可显著降低DN小鼠血糖,改善"三多一少"症状,增加胰岛素分泌,降低24 h尿蛋白、血清尿素氮和肌酐、血清和肾脏AGEs水平,缓解胰腺及肾脏病变,下调肾皮质RAGE m RNA和蛋白的表达。结论莫诺苷具有保护DN小鼠的作用,且高剂量作用较优,其相关机制可能与降低血清、肾脏AGEs水平,下调肾皮质RAGE m RNA和蛋白的表达有关。

Objective To observe the protective mechanism ofmorroniside （an active component in Comus officinalis） on the diabetic nephropathy （DN） mice induced by streptozocin （STZ） and aggravated by advanced glycation end products （AGEs）. Methods The DN mice were fed with high-AGEs fodders, and ig administered with aminoguanidine （0.1 g/kg）, metformin （0.2 g/kg）, captopril （0.02 g/kg）, low-dose morroniside （0.02 g/kg）, and high-dose morroniside （0.10 g/kg） for 12 weeks. After that, the fasting glucose, insulin, serum creatinine, urea nitrogen, serum and renal AGEs, 24＇h urine protein, etc were measured, the RT-PCR method was used to detect the levels of receptor for advanced glycation end products （RAGE） mRNA, the Western blotting technique was used to test the protein expression levels, and the pathologic changes of mice pancreas and kidney were observed. Results Morroniside could significantly decrease the fasting blood glucose levels, alleviate the symptoms of polydipsia, polyphagia, polyuria, and weight loss, increase the insulin production, and reduce the levels of 24 h urine protein, serum urea nitrogen, creatinine, sentrn and renal AGEs. Furthermore, morroniside could also anesis the lesions of pancreas and kidney and reduce the levels of RAGE mRNA and protein expression in renal cortex. Conclusion Morroniside has the protactive effects on DN mice and high-dose morroniside was much better. The mechanism may be related to the reduced levels of AGEs and RAGE mRNA and protein expression.