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用腹腔注射链脲佐菌素(streptozotocin,STZ)的方法制备大鼠糖尿病模型,观察羟苯磺酸钙对大鼠早期糖尿病肾病的肾脏保护作用。雄性Wistar大鼠随机分为正常对照组、DN空白对照组、羟苯磺酸钙75、150及300mg·kg-1组、培哚普利0.4mg·kg-1组。给药8周。动态检测各组大鼠血糖、24h尿白蛋白,末次给药后测定大鼠糖化血红蛋白(HbA1c),用放射免疫法测定血浆及肾皮质内皮素(ET)含量,用免疫组化技术检测肾皮质纤溶酶原激活物抑制剂-1(PAI-1)、基质金属蛋白酶-9(MMP-9)的表达,光镜、电镜下观察肾脏病理形态的改变。结果显示:羟苯磺酸钙能降低早期DN大鼠24h尿白蛋白及血浆和肾皮质ET水平,降低肾脏局部PAI-1表达,升高MMP-9表达。羟苯磺酸钙可以保护血管内皮,抑制肾脏纤维化,减轻肾脏病理损伤,从而保护大鼠肾脏功能。
The rat model of diabetes was induced by intraperitoneal injection of streptozotocin (STZ), and the renal protective effect of calcium dobesilate on diabetic nephropathy in rats was observed. Male Wistar rats were randomly divided into normal control group, DN blank control group, calcium dobesilate 75,150 and 300 mg · kg-1 group, perindopril 0.4 mg · kg-1 group. Administered for 8 weeks. The blood glucose of rats in each group was measured dynamically, urinary albumin was detected 24h, HbA1c was measured after the last administration, the content of endothelin (ET) in plasma and renal cortex was detected by radioimmunoassay, and renal cortex was detected by immunohistochemistry The expression of PAI-1 and MMP-9 were detected by light microscope and electron microscope. The pathological changes of kidney were observed. The results showed that calcium dobesilate could decrease the levels of urinary albumin and plasma ET and ET in early DN rats, decrease the expression of PAI-1 in the kidney and increase the expression of MMP-9. Calcium dobesilate can protect the vascular endothelium, inhibit renal fibrosis, reduce renal pathological damage, thereby protecting rat kidney function.