rhGLP-1(7-36)对糖尿病肾病大鼠肾脏的保护机制研究

目的 探讨rhGLP-1（7-36）对糖尿病肾病（diabetic kidney disease，DKD）大鼠肾脏的保护机制。方法 DKD模型大鼠随机分成模型组、rhGLP-1（7-36）低剂量组（20 μg·kg^-1）、rhGLP-1（7-36）中剂量组（40 μg·kg^-1）、rhGLP-1（7-36）高剂量组（80 μg·kg^-1），另设正常组，皮下注射给药4周。全自动生化分析仪检测24 h尿微量白蛋白、血肌酐及尿肌酐水平，计算肌酐清除率；进行腹腔糖耐量实验并计算药时曲线下面积（area under the cure，AUC）；HE染色行肾组织病理形态学观察；Western blotting检测肾组织SIRT1蛋白水平。结果 与模型组相比，rhGLP-1（7-36）高剂量组大鼠肌酐清除率有明显改善（P<0.05）；24 h尿微量白蛋白水平明显下降（P<0.05）；腹腔糖耐量AUC水平明显减小（P<0.05）；肾组织病理变化有不同程度改善；肾组织SIRT1蛋白水平明显上升（P<0.05）。结论 rhGLP-1（7-36）能有效改善DKD大鼠的肾脏功能，其机制可能与上调肾脏组织的SIRT1水平有关。

Study on Protective Mechanism of rhGLP-1(7-36) on Kidney of Rats with Diabetic Kidney Disease

OBJECTIVE To explore the protective mechanism of rhGLP-1(7-36) on the kidney of diabetic kidney disease (DKD) rats. METHODS DKD model rats were randomly divided into model group, rhGLP-1(7-36) low dose group (20 μg·kg^-1), rhGLP-1(7-36) medium dose group(40 μg·kg^-1), rhGLP-1(7-36) high dose group(80 μg·kg^-1), another normal group. Subcutaneous injection was administered for four weeks. Full-automatic biochemical analyzer was used to detect urine microalbumin, serum creatinine, and urinary creatinine levels for 24 h, calculated creatinine clearance. The area under the curve(AUC) was calculated by intraperitoneal glucose tolerance test. HE staining was used to observe the pathological and morphological changes of renal tissue. Western blotting was used to detect the level of SIRT1 protein in kidney tissue. RESULTS Compared with the model group, the creatinine clearance of the rats in the rhGLP-1(7-36) high dose group was significantly improved; the 24 h urine level was significantly reduced(P<0.05); the AUC of intraperitoneal glucose tolerance was significantly reduced(P<0.05); the pathological changes of renal tissue were improved to varying degrees; SIRT1 protein level in renal tissue was significantly increased(P<0.05). CONCLUSION rhGLP-1(7-36) can effectively improve the renal function of DKD rats, and the mechanism may be related to the up-regulation of SIRT1 level in kidney tissue.