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目的 观察血管紧张素Ⅱ (ATⅡ )受体拮抗剂L 15 880 9对 2型糖尿病大鼠模型肾脏的保护作用 ,并探讨其作用机制。方法 2型糖尿病大鼠在L 15 880 9治疗 16周后 ,测定肾组织ATⅡ含量 ,利用组织学检查观察肾组织结构的改变 ,免疫组化观察基质金属蛋白酶 2 (MMP 2 )及其金属蛋白酶 2组织抑制剂 (TIMP 2 )在肾小球的表达 ,酶谱法测定肾皮质MMP 2的活性 ,Western印迹检测肾皮质TIMP 2的含量。结果 L 15 880 9治疗使糖尿病大鼠血浆和肾皮质ATⅡ浓度进一步升高 ,肾小球基质增生明显减轻 ,肾小球MMP 2染色强度和肾皮质MMP 2的活性增强 ,但不能使肾小球TIMP 2染色及肾皮质TIMP 2含量降至正常。结论 L 15 880 9对类似人类 2型糖尿病大鼠肾脏病变有保护作用 ,对肾脏细胞外基质沉积的改善部分是通过促进基质转化而实现的。
Objective To observe the protective effect of angiotensin Ⅱ (ATⅡ) receptor antagonist L 15 880 9 on the kidney of type 2 diabetic rats and to explore its mechanism. Methods The type Ⅱ diabetic rats were treated with L 15 880 9 for 16 weeks. The content of ATⅡ in renal tissue was measured. The changes of renal structure were observed by histological examination. The expression of matrix metalloproteinase 2 (MMP 2) and metalloproteinase 2 The expression of tissue inhibitor of metalloproteinase (TIMP-2) in glomerulus was assayed. The activity of MMP 2 in renal cortex was detected by zymography. The content of TIMP 2 in renal cortex was detected by Western blotting. Results The treatment with L 15 880 9 increased the concentration of ATⅡ in the plasma and renal cortex of diabetic rats, and significantly reduced the glomerular matrix hyperplasia. The staining intensity of glomerulus MMP 2 and the activity of MMP 2 in renal cortex were enhanced, but not in glomeruli TIMP 2 staining and renal cortex TIMP 2 levels decreased to normal. Conclusion L 15 880 9 has a protective effect on renal lesions in a similar human type 2 diabetic rat. Part of the improvement in the extracellular matrix deposition of the kidney is partly mediated through the promotion of stromal transformation.