芒果苷对糖尿病大鼠肾脏的保护作用及机制

Protective Effect of Mangiferin on Kidney in Diabetic Rats

目的研究芒果苷对糖尿病大鼠肾损伤的保护作用及机制。方法利用腹腔注射链脲佐菌素诱导建立糖尿病大鼠模型,并进行随机分组:正常对照组、糖尿病模型组及低[15 mg/(kg.d)]、中[30 mg/(kg.d)]和高剂量[60 mg/(kg.d)]芒果苷组。12周时,检测肾重、肾脏肥大指数、血糖、24 h尿蛋白量,观察肾组织形态改变,免疫组织化学法和Western Blotting法测定肾组织转化生长因子β、基质金属蛋白酶2和组织型金属蛋白酶抑制剂2的表达。结果与正常对照组大鼠相比,糖尿病组肾脏肥大指数、24 h尿蛋白量显著上升;肾组织中转化生长因子β和组织型金属蛋白酶抑制剂2表达均明显增加,而基质金属蛋白酶2表达则明显降低。与糖尿病组相比,芒果苷治疗组肾脏肥大指数、24 h尿蛋白量显著下降(P<0.01);肾组织中转化生长因子β和组织型金属蛋白酶抑制剂2表达均明显减少(P<0.05或P<0.01),而基质金属蛋白酶2表达明显升高(P<0.05或P<0.01)。结论芒果苷对链脲佐菌素诱导的糖尿病肾损伤具有明显的保护作用,其机制可能与调节糖尿病肾病发病中的细胞外基质组成有关,其中转化生长因子β、组织型金属蛋白酶抑制剂2和基质金属蛋白酶2在糖尿病肾病变发生、发展中具有重要作用。

Aim To investigate the therapeutic effects of mangiferin on experimental diabetic nephropathy in rats,and explore the underlying mechanism. Methods The diabetic rats was induced by intraperitoneal injection with streptozotocin（STZ）.The rats were randomly divided into five groups： the normal control group,the diabetic model group,the low（15 mg/（kg·d））,middle（30 mg/（kg·d））,high（60 mg/（kg·d）） doses of mangiferin therapy group.Renal weight,index number of kidney hypertrophy,fasting blood glucose and 24-hour urinary protein excretion were examined at 12 weeks.The structure of kidney was analyzed by light microscope.Immunohistochemistry and Western Blotting were used to detect the expression of transforming growing factor-β（TGF-β）,matrix metalloproteinases-2（MMP-2）,tissue inhibitors of matrix metalloproteinase-2（TIMP-2） in renal tissues. Results Compared with normal control group,the index number of kidney hypertrophy and 24-hour urinary protein were significantly up-regulated in the diabetic group;the protein expression of TGF-β and TIMP-2 were significantly up-regulated while MMP-2 was significantly decreased.Compared with the diabetic group,index number of kidney hypertrophy and 24-hour urinary protein were significantly decreased in mangiferin therapy groups（P0.01）;the protein expression of TGF-β and TIMP-2 were significantly decreased（P0.05 or P0.01）,MMP-2 was significantly up-regulated（P0.05 or P0.01）. Conclusion The expression of TGF-β,MMP-2 andTIMP-2 are related to diabetic nephropathy（DN）,mangiferin has protective effect on kidney of diabetic rats through affecting the changes of above mentioned indexes.