【摘要】 目的 :探讨抗坏血酸对糖尿病大鼠肾脏金属蛋白酶组织抑制因子 - 1(TIMP - 1)mRNA和蛋白表达的影响。方法 :实验大鼠随机分为 3组 :对照组 (C组 )、糖尿病组 (D组 )、糖尿病 +抗坏血酸 90mg/kg/d(DT组 ) ,实验第 9周检测血浆、肾脏抗坏血酸水平和醛糖还原酶 (AR)活性 ,同时用原位杂交和Western -blot检测TIMP - 1mRNA和蛋白表达水平。结果 :与正常对照组比较 ,糖尿病组血浆、肾脏抗坏血酸水平显著下降 (P <0 .0 5 ) ,肾脏AR活性明显升高 ,TIMP - 1mRNA和蛋白表达明显增加 (P均 <0 .0 1)。抗坏血酸治疗组血浆、肾脏抗坏血酸水平和正常对照组比较差异无显著性 ,AR活性、TIMP -1mRNA和蛋白表达水平较糖尿病组明显降低 (P均 <0 .0 1)。结论 :补充抗坏血酸可显著增加糖尿病大鼠血浆、肾脏抗坏血酸水平 ,明显降低糖尿病大鼠肾皮质AR活性、TIMP - 1mRNA和蛋白表达水平 ;多元醇途径可能部分介导了糠尿病大鼠肾脏TIMP - 1mRNA和蛋白表达。更多还原

【Abstract】 Objective:To explore the effects of ascorbic acid on the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA and protein in renal cortex in rats with streptozotocin-induced diabetes. Methods: 30 male Wistar rats(195±20g)were randomly divided into following groups:group C(control rats);group D(diabetic rats);and group DT(diabetic rats treated with ascorbic acid 90mg/kg·d).The concentrations of ascorbic acid and activity of aldose reductase (AR) in plasma and renal cortex were assayed at 9 weeks.In addition ,the protein expression of TIMP-1 in renal cortex was determined by Western-blot and the mRNA expression of TIMP-1 was measured by hybridization in situ. Results: Compared with group C,the levels of ascorbic acid in plasma and kidney decreased significantly in group D( P <0.01)?The activity of aldose reductase ,and the expressions of TIMP-1 mRNA and protein increased markedly ( P<0.01,respectively).The concentrations of ascorbic acid in plasma and kidney increased to normal level,and the others were markedly ameliorated after 8 weeks treatment with ascorbic acid in group DT. Conclusion:The findings suggest that administration of ascorbic acid can increase the levels of ascorbic acid and lower the expressions of TIMP-1 mRNA and protein in renal cortex in rats with streptozotocin-induced diabetes,and diabetes-induced expressions of TIMP-1 mRNA and protein may be mediated in part by polyol pathway.更多还原