槲皮素脂质体对糖尿病大鼠肾脏糖基化终产物及其受体表达的影响

摘要

Objective To observe the effects of quercetin liposome (LQ) on formation of advanced glycation end prod-ucts(AGEs)and receptor for advanced glycation end products (RAGE) in kidney of diabetic rats. Methods LQ was made by rotary evaporation, and the model of type 2 diabetic rats were established by being fed on high-sugar and high-fat diet combined with intraperitoneally injection of streptozotocin (STZ). Then type 2 diabetic rats were randomly divided into six groups:diabetic model group (group DM), low level of LQ group (group LQ-L ), medium level of LQ group (group LQ-M), high level of LQ group (group LQ-H), positive control group (group aminoguanidine, AG) and control group (group N). After 8 weeks of interventions, blood glucose, body weight, kidney hypertrophy index (KI), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured in each group. ELISA was used to detect serum AGEs, and 24 h urine albumin. The pathologi-cal change of glomerular basement membranes was observed by PAS staining and the expressions of AGEs in kidney was as-sessed by immunohistochemical method. The transcription level of RAGE mRNA in kidney was determined by RT-PCR. Re-sults Compared with the group N, the level of blood glucose, KI, BUN, Scr, serum AGEs and 24 h urine albumin were in-creased significantly in group DM, while the level of body weight decreased. Also the volume of kidney glomerulus increased and glomerular basement membranes thickened, the transcription levels of AGEs and RAGE mRNA in kidney tissue in-creased in DM group (P<0.05). Compared with group DM, the level of blood glucose, KI, BUN, Scr, serum AGEs and 24 h urinary albumin decreased, while the level of body weight increased in all three LQ groups. Meantime, the change of patho-logical morphology of glomerular basement membranes reduced and the expressions of AGEs and RAGE mRNA in kidney tissue decreased in all three LQ groups. All changes in the medium LQ dose group were more obvious than those of other two LQ groups (P<0.05). Conclusion Similar to AG, LQ has effect on inhibiting the action of proteinum unenzymatic glycosyl-ation and on decreasing the production of AGEs in serum as well as the expression of RAGE mRNA in kidney. Therefore, LQ play important protective role in kidneys of diabetic rats.%目的 观察槲皮素脂质体(LQ)对糖尿病大鼠肾脏糖基化终产物(AGEs)及其受体(RAGE)表达的影响.方法 采用旋转蒸发法制备槲皮素脂质体,高糖高脂饲料联合腹腔注射链脲佐菌素(STZ)建立2型糖尿病大鼠模型,并随机分为糖尿病模型组(DM组),槲皮素脂质体低(LQ-L)、中(LQ-M)、高(LQ-H)剂量组,氨基胍(AG)对照组(AG组),另设正常组(N组).灌胃治疗8周后测定各组大鼠血糖、体质量、肾脏肥大指数(KI)、血尿素氮(BUN)、血肌酐(Scr),ELISA法测血清AGEs表达和24 h尿微量白蛋白,PAS染色观察肾脏病理改变,免疫组化测肾组织AGEs表达,RT-PCR检测肾皮质RAGE mRNA表达水平.结果 与N组比较,DM组大鼠血糖、KI、BUN、Scr、血清AGEs和24 h尿微量白蛋白显著升高,体质量明显降低;肾小球体积萎缩,基底膜增厚;肾组织AGEs和RAGE mRNA表达增高(均P<0.05).与DM组比较,LQ各剂量组大鼠血糖、KI、BUN、Scr、血清AGEs和24 h尿微量白蛋白均降低,体质量增加;病理改变明显减轻;肾组织AGEs和RAGE mRNA表达降低,以中剂量组作用更明显(均P<0.05).结论 LQ可抑制蛋白质非酶糖基化反应,从而减少肾组织AGEs生成及RAGE mRNA表达水平,对糖尿病大鼠肾脏具有保护作用.