Objective: 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.
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。.
Keywords: Diabetic nephropathy; Insulin-like growth factor 1; Insulin-like growth factor binding protein 3; Mulberry leaf polysaccharide.