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伞形酮——香豆素衍生物——减弱 I 型糖尿病大鼠的肾损伤。

Attenuation of renal damage in type I diabetic rats by umbelliferone - a coumarin derivative.

机构信息

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Mumbai, India.

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Mumbai, India.

出版信息

Pharmacol Rep. 2017 Dec;69(6):1263-1269. doi: 10.1016/j.pharep.2017.06.014. Epub 2017 Jun 27.

Abstract

BACKGROUND

It is well known that diabetes is one of the non-communicable disease affecting a large population worldwide. When diabetes remains untreated or uncontrolled, it leads to further serious complications, affecting vital organs like eyes, kidney, heart, etc. The present study was designed to evaluate effects of umbelliferone, a phytochemical, in treatment of diabetic nephropathy.

METHODS

Experimental model used was streptozotocin (55mg/kg, ip) induced diabetic nephropathy in male Sprague Dawley rats. After 28days of streptozotocin administration, diabetic animals were treated with umbelliferone at two dose levels, 20 and 40mg/kg for next 28days.

RESULTS

The results of the study showed that umbelliferone treatment significantly decreased the elevated plasma creatinine and blood urea nitrogen level while significantly increased the total protein and albumin level in diabetic animals. Creatinine clearance was improved in umbelliferone treated animals. Renal oxidative stress was decreased in umbelliferone treated animals significantly. Histopathological study of the kidney was carried out by specific stains like Hematoxylin-Eosin, Periodic Acid Schiff and Masson Trichrome stain. The sections of the kidney showed that umbelliferone treatment decreased the glomerular damage, mesangial matrix expansion as well as the renal fibrosis. Determination of renal transforming growth factor beta one (TGF-β1) expression by immunohistochemical analysis, western blotting and circulating TGF-β1 by ELISA assay showed that umbelliferone decreased the renal tissue and circulating TGF-β1 level.

CONCLUSION

Umbelliferone treatment can significantly reduce the diabetes induced renal damage and can improve the pathological conditions related to the diabetic nephropathy by down regulation of TGF-β.

摘要

背景

众所周知,糖尿病是影响全球大量人口的非传染性疾病之一。当糖尿病得不到治疗或控制时,会导致进一步的严重并发症,影响到眼睛、肾脏、心脏等重要器官。本研究旨在评估植物化学物质伞形酮治疗糖尿病肾病的效果。

方法

实验模型使用链脲佐菌素(55mg/kg,ip)诱导雄性 Sprague Dawley 大鼠糖尿病肾病。链脲佐菌素给药 28 天后,用伞形酮以 20 和 40mg/kg 两个剂量水平对糖尿病动物进行治疗,持续 28 天。

结果

研究结果表明,伞形酮治疗可显著降低糖尿病动物升高的血浆肌酐和血尿素氮水平,同时显著增加总蛋白和白蛋白水平。伞形酮治疗组的肌酐清除率得到改善。伞形酮治疗组的肾脏氧化应激显著降低。通过苏木精-伊红、过碘酸希夫和 Masson 三色染色等特殊染色对肾脏进行组织病理学研究。肾脏切片显示,伞形酮治疗可减少肾小球损伤、系膜基质扩张以及肾纤维化。通过免疫组织化学分析、Western 印迹和 ELISA 测定循环 TGF-β1 测定,确定肾转化生长因子β 1(TGF-β1)的表达,结果表明伞形酮降低了肾组织和循环 TGF-β1 水平。

结论

伞形酮治疗可显著减轻糖尿病引起的肾脏损伤,并通过下调 TGF-β 改善与糖尿病肾病相关的病理状况。

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