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四氧嘧啶糖尿病大鼠诱导的肾损伤。霉酚酸酯作为治疗剂的作用。

Renal injury induced in alloxan diabetic rats. Role of Mycophenolate Mofetil as therapeutic agent.

作者信息

Elseweidy Mohamed M, Elswefy Sahar E, Ali Abd Elmoniem, Shawky Mohamed

机构信息

Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

Pathology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.

出版信息

Pathol Res Pract. 2014 Dec;210(12):979-84. doi: 10.1016/j.prp.2014.05.014. Epub 2014 May 23.

DOI:10.1016/j.prp.2014.05.014
PMID:24939145
Abstract

BACKGROUND

Renal injury may develop in uncontrolled chronic hyperglycemia due to increased oxidative stress and release of pro-inflammatory mediators, leading to diabetic complications.

METHODS

Mycophenolate Mofetil (MMF) is an immunosuppressant drug, an inhibitor of inosine monophosphate dehydrogenase (IMPDH), relevant to inflammation processes. MMF effect was tested in alloxan-diabetic rats on selected parameters like oxidative stress, gene expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1), in relation to microalbuminuria and renal function.

RESULTS

We found that the onset of microalbuminuria preceded the increase in serum glucose after alloxan treatment. Gene expression of TNF-α and TGF-β1 showed gradual increase after one and two weeks of alloxan administration as compared to the normal group. MMF administration decreased the gene expression of TNF-α and TGF-β1 in kidney tissues, serum glucose, fructosamine, urea, creatinine, C-reactive protein, malondialdehyde, urinary microalbumin and total protein. Histological examination of kidney tissues showed significant improvement in MMF treated rats as compared to diabetic control.

CONCLUSIONS

MMF modulated renal injury of alloxan diabetic rats. Collective data may support its therapeutic effect but further clinical trials may be requested.

摘要

背景

由于氧化应激增加和促炎介质释放,未控制的慢性高血糖可能导致肾损伤,进而引发糖尿病并发症。

方法

霉酚酸酯(MMF)是一种免疫抑制剂,是肌苷单磷酸脱氢酶(IMPDH)的抑制剂,与炎症过程相关。在四氧嘧啶诱导的糖尿病大鼠中,就氧化应激、肿瘤坏死因子-α(TNF-α)和转化生长因子-β1(TGF-β1)的基因表达等选定参数,检测MMF对微量白蛋白尿和肾功能的影响。

结果

我们发现,四氧嘧啶治疗后,微量白蛋白尿的出现先于血糖升高。与正常组相比,四氧嘧啶给药1周和2周后,TNF-α和TGF-β1的基因表达呈逐渐增加。给予MMF后,肾组织中TNF-α和TGF-β1的基因表达、血糖、果糖胺、尿素、肌酐、C反应蛋白、丙二醛、尿微量白蛋白和总蛋白均降低。与糖尿病对照组相比,MMF治疗大鼠的肾组织组织学检查显示有显著改善。

结论

MMF可调节四氧嘧啶糖尿病大鼠的肾损伤。总体数据可能支持其治疗效果,但可能需要进一步的临床试验。

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