摘要
目的 观察不同剂量盐酸吡咯列酮对单肾切除糖尿病大鼠模型慢性肾脏损害的作用。方法 采用单肾切除的小剂量链脲佐菌素诱导性糖尿病大鼠 ,随机均分为单肾切除对照 (CTR)组、糖尿病非治疗 (DM )组、3mg·kg-1·d-1吡咯列酮 (DM LP)治疗组、9mg·kg-1·d-1吡咯列酮治疗组和 2 0mg·kg-1·d-1吡咯列酮治疗组共 5组。药物灌胃 10周 ,收集2 4h尿液标本 ,测定血糖和动脉收缩压后处死大鼠 ,并留取血标本和肾脏组织。结果 与CTR组相比 ,另 4组糖尿病大鼠的血清胰岛素水平均明显降低 ,DM组表现出明显的高糖和高脂血症 ,动脉收缩压、2 4h尿蛋白量、肾小球细胞外基质(ECM)沉积和相对肾重均明显升高。 3mg·kg-1·d-1吡咯列酮在不影响血糖、血脂和血压的情况下 ,能明显减轻蛋白尿和肾小球ECM沉积 ,降低相对肾重 ;9mg·kg-1·d-1吡咯列酮能明显改善血糖和高三酰甘油血症 ,但不影响动脉收缩压和高胆固醇血症 ,其减轻蛋白尿和肾小球ECM沉积以及降低相对肾重的作用与 3mg·kg-1·d-1剂量治疗组的差异无显著性 ;2 0mg·kg-1·d-1吡咯列酮除有与 9mg·kg-1·d-1剂量相似程度改善高血糖和高三酰甘油血症的作用外 ,还能明显降低大鼠动脉收缩压 ;其减轻蛋白尿、肾小球ECM沉积和肾脏肥大的作用较 3和
Objective To observe the effects of different dosages of pioglitazone on uninephrectomized diabetic rats. Methods Male uninephrectomized Wistar rats were randomly allocated to five groups: non diabetic control rats (CTR), diabetic rats without treatment (DM), 3, 9 and 20 mg·kg -1 ·d -1 pioglitazone treated diabetic rats (DM LP, DM MP and DM HP respectively). After 10 weeks of drug gavage, blood glucose, systolic blood pressure (SBP) serum triglyceride (TG), serum total cholesterol (TC), serum insulin level, 24 hour urinary protein excretion and kidney hypertrophy index (LK/BW) were evaluated. Periodic acid schiff (PAS) stain was also used to measure the glomerular extracellular matrix (ECM) deposition. Results Comparing with CTR, DM demonstrated hyperglycemia, hyperlipidemia, hypertension and significantly increased urinary protein excretion and LK/BW. Contrary to DM, DM LP showed no changes in blood glucose, serum TG and CHO and SBP, but the proteinuria and glomerular ECM deposition were ameliorated significantly. Comparing with DM, DM MP had greatly attenuated BG and serum TG, but not SBP and TC; its proteinuria and ECM deposition were similar to those of DM LP. Besides the comparable control of BG and serum TG, DM HP showed a decline in SBP comparing with DM MP, there was further attenuation of proteinuria and pathological progress in this group. Conclusion Different dosages of pioglitazone might have diverse effects on the uninephrectomized diabetic rats. 3 mg·kg -1 ·d -1 pioglitazone is beneficial and independent of its metabolic effects. Although 9 mg·kg -1 ·d -1 pioglitazone ameliorates the metabolic disorder in diabetic rats, it fails to show delay of nephropathy in comparing with 3 mg·kg -1 ·d -1 . 20 mg·kg -1 ·d -1 pioglitazone can ameliorate the hypertension of uninephrectomized diabetic rats, its effects of decreasing the proteinuria and delaying the progression of renal pathologic charge are augmented further.
出处
《上海医学》
CAS
CSCD
北大核心
2003年第11期797-800,共4页
Shanghai Medical Journal
基金
国家自然科学基金资助项目 (3 0 2 0 0 12 5 )
