摘要目的 观察桑叶多糖对1型糖尿病肾病大鼠血清胰岛素样生长因子1(IGF-1)和胰岛素样生长因子结合蛋白3(IGFBP-3)及肾脏IGF-1和IGFBP-3 mRNA表达的影响,并探讨其对1型糖尿病肾病的疗效及可能机制.方法 大剂量链脲佐菌素建立1型糖尿病肾病大鼠模型. SD大鼠随机分为正常对照组、模型组、胰岛素组、桑叶多糖组,每组8只.桑叶多糖组给予桑叶多糖200 mg· kg-1· d-1灌胃,胰岛素组给予短效胰岛素1 U/d皮下注射,干预时间为8周.检测血液和尿液相关指标,计算体重变化量和肾小球细胞外基质的相对面积,酶联免疫吸附法测定血清IGF-1和IGFBP-3,荧光定量PCR检测肾脏IGF-1、IGFBP-3 mRNA的表达量.结果 干预8周后,与对照组比较,模型组大鼠血糖、三酰甘油、总胆固醇、低密度脂蛋白、极低密度脂蛋白、24 h尿蛋白、血肌酐、尿素氮均明显升高,差异均有统计学意义(均P＜0.01),而桑叶多糖组与模型组比较上述指标均明显降低,差异均有统计学意义(均P＜0.01).模型组大鼠与对照组比较血清IGF-1 和IGFBP-3 水平升高(均P＜0.001),而桑叶多糖组与模型组比较血清IGF-1[(0.777 ±0.018) ng/ml比(0.864 ±0.022) ng/ml, P＜0.001]和IGFBP-3[(0.759 ±0.016) ng/ml比(0.846 ±0.021) ng/ml,P＜0.001]均降低.模型组大鼠与对照组相比肾脏IGF-1和IGFBP-3 mRNA表达增加(均P＜0.001),而桑叶多糖组与模型组比较肾脏IGF-1 (1.450 ±0.032 比1.810 ±0.090, P＜0.001)和 IGFBP-3 (1.684 ±0.018 比1.968 ± 0.044,P＜0.001)mRNA表达水平减少.与模型组比较,桑叶多糖组的肾脏病理变化较小.结论 桑叶多糖对糖尿病肾病有一定的治疗作用,其作用机制可能是通过减少血清IGF-1和IGFBP-3及下调肾脏IGF-1和IGFBP-3 mRNA的过度表达来实现.

abstractsObjective To observe the effects of mulberry leaf polysaccharide ( MLP) on insulin-like growth factor 1 ( IGF-1) and insulin-like growth factor blinding protein 3 ( IGFBP-3) as well as the expression of IGF-1 and IGFBP-3 mRNA in the kidney of type 1 Diabetic Nephropathy ( DN) rats, and to investigate its therapeutic effects and underlying mechanisms .Methods Type 1 DN rat model was established by intraperitoneally injecting streptozocin ( STZ ) .SD rats were randomly divided into the control, model, insulin and MLP groups, with eight rats in each group.Rats in MLP group were given orally with MLP 200 mg/kg daily for 8 weeks and insulin group rats were given subcutaneously injection of short acting insulin 1 U daily for 8 weeks.The changes in body weight , blood and urine parameters were recorded.Extracellular matrix (ECM) was calculated.The contents of IGF-1 and IGFBP-3 in blood serum were evaluated by enzyme-linked immunosorbent assay ( ELISA) .The mRNA expressions of IGF-1 and IGFBP-3 in the kidney were evaluated by fluorescence quantitative PCR .Results Compared with rats in control group, blood glucose, triglyceride, total cholesterol, low density lipoprotein, very low density lipoprotein, 24 h urine protein, serum creatinine and urea nitrogen in the model group rats were significantly increased (all P＜0.01), and these parameters of MLP group were significantly lower than the model group ( all P＜0.01).The contents of IGF-1 and IGFBP-3 in the blood serum of the model group were significantly higher than those in the control group (both P＜0.001), while in the MLP group they were lower than the model group[IGF-1:(0.777 ±0.018) ng/ml vs (0.864 ±0.022) ng/ml, P＜0.001; IGFBP-3: (0.759 ± 0.016) ng/ml vs (0.846 ±0.021) ng/ml, P＜0.001].The mRNA expressions of IGF-1 and IGFBP-3 in the kidney of the model group were significantly higher than those in the control group ( both P＜0.001), while in the MLP group they were lower than in the model group (IGF-1: 1.450 ±0.032 vs 1.810 ±0.090, P＜0.001; IGFBP-3: 1.684 ±0.018 vs 1.968 ±0.044, P＜0.001).Compared with the model group rats , there were fewer pathological changes of kidney in MLP group rats .Conclusion MLP has a certain therapeutic effect on DN, which may be achieved by decreasing the contents of IGF-1 and IGFBP-3 in the blood serum and down-regulating the over-expression of IGF-1 and IGFBP-3 mRNA in the kidney.