羟苯磺酸钙对早期糖尿病肾病大鼠肾脏的保护作用  

Protective effect of calcium dobesilate against early diabetic nephropathy of rat kidney

作　　者：高美娟[1] 刘明[2] 李波[1] 李明龙[3] 卞丽香[1] 于桂娜[1] 

机构地区：[1]山东大学附属省立医院内分泌科,山东济南250021 [2]山东大学附属省立医院核医学科,山东济南250021 [3]山东大学附属省立医院保健科,山东济南250021

出　　处：《药学学报》2009年第2期126-133,共8页Acta Pharmaceutica Sinica

基　　金：山东省科技厅资助项目(2001BB1DBA1)

摘　　要：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 aim of this study is to study the effect of calcium dobesilate on streptozotocin （STZ）-induced early diabetic nephrophathy （DN） in rats. All male Wistar rats were randomly divided into six groups： normal group; DN blank group; calcium dobesilate 75, 150, and 300 mg·kg^-1 groups and perindopril 0.4 mg·kg^-1 group. Blood glucose and the 24 h urinary albumin were measured dynamically during the experiment, after 8 weeks administration, the level of glycosylated hemoglobin （HbAlc） was determined, the expressions of plasminogen activator inhibitor-1 （PAI-1） and matrix metalloprotein-9 （MMP-9） in cortex of kidney were examined with immunohistochemical staining. The endothelin （ET） in plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism was observed with light and electron microscopes. Calcium dobesilate could decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down-regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings suggested that calcium dobesilate could protect blood vessel endothelium, inhibit kidney fibrous degeneration, ameliorate renal pathological damage, and protect kidney function in many ways.

关 键 词：羟苯磺酸钙 糖尿病肾病 血管紧张素转换酶抑制剂 纤溶酶原激活物抑制剂-1 基质金属蛋白酶-9 内皮素 

分 类 号：R963[医药卫生—微生物与生化药学]