羟苯磺酸钙改善糖尿病大鼠视网膜病变及其机制研究

Improvement of calcium dobesilate on diabetic retinopathy in rats and its mechanism

目的观察羟苯磺酸钙对糖尿病大鼠视网膜病变的影响并探讨其机制。方法以65 mg/kg一次性ip链脲佐菌素诱导糖尿病模型,将糖尿病模型大鼠分为模型组、复方血栓通组(1.05 g/kg)和羟苯磺酸钙组(0.334 g/kg),另设对照组,均ig给药,1次/d,对照组给予等剂量蒸馏水,共12周。采用Real-time PCR法检测Ⅳ型胶原及血管内皮生长因子(VEGF)m RNA在视网膜组织中的表达;光镜下观察视网膜血管形态学改变,测定视网膜毛细血管面积密度;透视电镜观察大鼠视网膜超微结构。结果与对照组比较,模型组大鼠视网膜Ⅳ型胶原m RNA表达升高(P<0.05),VEGF m RNA升高(P<0.01),毛细血管面积密度显著增高(P<0.001)。与模型组比较,羟苯磺酸钙组大鼠视网膜Ⅳ型胶原m RNA、VEGF m RNA表达和毛细血管面积密度均降低(P<0.05)。结论羟苯磺酸钙能下调视网膜中Ⅳ型胶原、VEGF的表达,抑制纤维组织增生和血管新生,从而改善糖尿病视网膜病变。

Objective To observe the effect of calcium dobesilate on the diabetic retinopathy in rats and to explore its mechanism. Methods Rats were ip administered with streptozotocin （65 mg/kg） to induce diabetes model. The diabetic rats were randomly divided into model group, Compound Xueshuantong group （1.05 g/kg）, and calcium dobesilate group （0.334 g/kg）. Other rats were recruited as the control group. The expression of collagen 1V mRNA and vascular endothelial growth factor （VEGF） mRNA in retinas of rats were determined by Real-time PCR method. The morphology was observed under light microscope, and retinal capillary areas were determined. The ultrastructure of retinal capillary was observed under electron microscope. Results Compared with the control group, the indexes of rats in model group such as collagen IV mRNA expression （P 〈 0.05）, VEGF mRNA expression （P 〈 0.01）, and capillary density （P 〈 0.001） significantly increased. Compared with the model group, collagen IV mRNA, VEGF mRNA expression, and capillary density in calcium dobesilate group were significantly decreased （P 〈0.05）. Conclusion Calcium dobesilate can down-regulate the expressions of collagen IV and VEGF in retinas of rats, restrain fibrous tissue hyperplasia and angiogenesis, thereby improve the diabetic retinopathy.