羟苯磺酸钙对糖尿病大鼠肾小球MMP9/TIMP1的影响

目的 观察羟苯磺酸钙对糖尿病(DM)大鼠肾小球基质金属蛋白酶9(MMP9)、金属蛋白酶组织抑制因子1(TIMP1)、胶原Ⅳ以及肾小球基底膜超微结构的影响。方法 糖尿病模型由Spregue-Dawley(SD)大鼠单肾切除联合腹腔注射链脲佐菌素(STZ)诱导，糖尿病给药组(DD组)每天给予羟苯磺酸钙100mg／kg。12周后观察各组大鼠肾脏超微结构的改变以及免疫组化检查肾组织MMP9、TIMP1和胶原Ⅳ表达的变化。结果 12周后电镜检查显示DD组肾小球毛细血管基底膜增厚轻于糖尿病对照组(DM组)，无胶原纤维的增生，内皮细胞孔距不及单肾切除对照组(NC组)均匀，但较DM组均匀，足细胞突起排列尚整齐，免疫组织化学显示DD组TIMP1、胶原Ⅳ明显低于DM组。结论 羟苯磺酸钙能抑制胶原Ⅳ过度积聚、减轻肾小球基底膜增厚，这可能与抑制糖尿病大鼠肾脏TIMP1表达、上调MMP9／TIMP1比值有关。

Effects of calcium dobesilate on glomerulus MMP9/TIMP1 of diabetic rats

Objective To investigate the effects of calcium dobesilate on the expression of glomeruli matrix metalloproteinases-9 (MMP-9),tissue inhibitor of metalloproteinase-1 (TIMP-1),collagen IV and ultrastructure of glomerular basement membrane in diabetic rats.Methods Rat diabetic model was established by unilateral nephrectomized and intraperitoneal injection STZ.The model rats accepted 100mg/kg calcium dobesilate (Group DD) or distilled water (Group DM).12 weeks later,the renal pathology and ultrastructure of kidneys were detected in both groups.Immunohistochemistry staining was employed to study the expression of glomerulus MMP-9,TIMP-1 and collagen IV.Results After 12 weeks,electron microscopy showed that thickness of glomerular capillary basement membrane in Group DD was less than that of Group DM.No hyperplasia of collagen fibers was found,the hole distance of endothelial cells is not so even as that of the normal group,but more even than that of Group DM, podocyte process is still in order. Immunohistochemistry staining of glomerulus showed that expressions of TIMP-1 and collagen IV in Group DD are obviously less than those in Group DM. Conclusion Calcium dobesilate can improve microangiopathy of diabetes mellitus by inhibiting the over-accumulation of collagen IV.Calcium dobesilate may also contribute to diabetes by inhibiting expression of TIMP-1,up-regulating the rate of MMP-9/TIMP-1.