摘要
目的 观察盐酸吡咯列酮对单肾切除的糖尿病大鼠肾脏纤维化的影响,并从纤维化相关基因表达改变的角度探讨其机制。方法 采用PAS、Northern blot和Western blot方法,检测口服吡咯列酮[3mg/(kg·d)]治疗对单肾切除的SIZ(35mg/kg)诱导性糖尿病大鼠模型的肾小球 ECM积聚情况,肾皮质中TGF-β1和TIMP-1的mRNA水平,以及PAI-1蛋白表达水平的作用。结果 与CTR和CTR+P组相比,DM的血糖、血脂、SBP和左肾/体重比均明显升高,肾小球ECM积聚程度明显增加,肾皮质中TGF-β1和TIMP-1的mRNA水平明显增加,PAI-1的蛋白含量也明显增加;与DM组相比,DM+P组的血糖、血脂和SBP无明显改变,但24h尿蛋白量、左肾/体重比和肾小球ECM积聚程度明显降低,肾皮质中TGF-β1和TIMP-1的mRNA水平明显降低,PAI-1的蛋白含量也明显降低。结论 吡咯列酮在不影响代谢的情况下能延缓单肾切除的糖尿病大鼠肾脏纤维化的进展。其作用机制可能与吡咯列酮能够抑制肾皮质中TGF-β1、TIMP-1和PAI-1的基因表达水平有关。
Purpose: To study the effects of pioglitazone on the renal fibrosis of uninephrectomized diabetic rats and its possible mechanisms. Methods: Uninephrectomized male Wistar rats (180 - 200 g) were randomly assigned to four groups: non-diabetic control rats (CTR), non-diabetic rats treated with 3 mg/ (kg·d) pioglitazone (CTR + P), low dose (35 mg/kg) streptozotocin-induced diabetic rats (DM), and 3 mg/(kg·d) pioglitazone-treated diabetic rats (DM + P). After 10 weeks of treatment, blood glucose, serum triglyceride, serum total cholesterol, systolic blood pressure (SBP), 24-hour urinary protein excretion and left kidney weight/body weight (LK/BW) were examined. Periodic acid-schiff (PAS) stain was used to measure the glomerular extracelluar matrix deposition. Northern blot was used to detect the mRNA levels of transforming growth factor (TGF)-β1 and tissue inhibitor of metalloproteinases (TIMP)-1 in renal cortex. The protein expressions of plasminogen activator inhibitor (PAI)-1 in the renal cortex were also measured by Western blot. Results: Compared with the CTR and the CTR + P, DM demonstrated hyperglycemia, hyperlipidemia, hypertension and significantly increased urinary protein excretion and LK/BW, extracellular matrix (ECM) was also increased in this group. These changes were associated with significantly upregulated TGF-β1 and TIMP-1 mRNA and PAI-1 protein expression in the renal cortex. Compared with the DM group, administration of pioglitazone significantly attenuated the proteinuria, increased LK/BW and ECM, but not hyperglycemia, hyperlipidemia and hypertension, it also ameliorated the upregulated mRNA levels of TGF-β1 and TIMP-1 and the increased protein expression of PAI-1. Conclusions: Our results suggested that pioglitazone might delay the renal fibrotic progress of the uninephrectomized diabetic rats without metabolic effects. The downregulated gene expression of TGF-β1, TIMP-1 and PAI-1 by pioglitazone might be involved.
出处
《复旦学报（医学版）》
EI
CAS
CSCD
北大核心
2003年第3期235-238,F004,共5页
Fudan University Journal of Medical Sciences
基金
上海市百人计划(98BR038)
上海市教委曙光计划基金(01SG08)
