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葡萄籽对链脲佐菌素诱导的糖尿病大鼠凋亡相关基因表达及氧化应激的影响。

The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats.

作者信息

Güçlü Aydın, Yonguç Nilüfer, Dodurga Yavuz, Gündoğdu Gülşah, Güçlü Zuhal, Yonguç Tarık, Adıgüzel Esat, Turkmen Kultigin

机构信息

Department of Nephrology, Ahi Evran University Training and Research Hospital , Kırşehir , Turkey .

出版信息

Ren Fail. 2015 Mar;37(2):192-7. doi: 10.3109/0886022X.2014.991996. Epub 2015 Jan 7.

DOI:10.3109/0886022X.2014.991996
PMID:25565258
Abstract

BACKGROUND

Diabetic nephropathy is the most common cause of end-stage renal disease. Emerging evidences indicate that many mechanistic pathways including apoptosis play an important role in the pathogenesis and progression of macrovascular and microvascular complications of diabetes mellitus. The aim of the present study is to show the effects of grape seed extract (GSE) on oxidative stress and apoptosis in the kidney of streptozotocin-induced diabetic rats.

MATERIALS AND METHODS

The study included control group, diabetic group without treatment and diabetic group treated with GSE (n=7) group. GSE was given orally (100 mg/kg/day) for six weeks. Following parameters were evaluated; oxidative stress index, caspase 1, IL1-alpha, caspase 2, IL1-beta, BCL2-associated agonist of cell death (BAD), X-linked inhibitor of apoptosis (XIAP), DNA fragmentation factor, alpha subunit and beta bubunit (DFFA, DFFB), BH3 interacting domain death agonist (BID), caspase 6, Bcl2-like 1 (BCL-XL), caspase 8, tumor necrosis factor receptor superfamily, member 1 b (TNFRSF1B) and IAP-binding mitochondrial protein (DIABLO).

RESULTS

Oxidative stress index levels were significantly increased in the kidney of diabetic group without treatment compared to control group, and decreased in diabetic+GSE group compared to diabetic group without treatment. In the kidney of diabetic group without treatment, caspase 1, IL-1 alpha, BAD, DFFA, DFFB and caspase-6 gene expressions were significantly higher compared to control group. In diabetic+GSE group caspase 1, caspase 2, XIAP, DFFA, BID, BCL-XL and TNFRSF1B genes were significantly decreased compared to control group.

CONCLUSIONS

Grape seed reduces oxidative stress and apoptosis gene expression suggesting the protective effect on diabetic nephropathy.

摘要

背景

糖尿病肾病是终末期肾病最常见的病因。新出现的证据表明,包括细胞凋亡在内的许多机制途径在糖尿病大血管和微血管并发症的发病机制及进展中起重要作用。本研究的目的是展示葡萄籽提取物(GSE)对链脲佐菌素诱导的糖尿病大鼠肾脏氧化应激和细胞凋亡的影响。

材料与方法

该研究包括对照组、未治疗的糖尿病组和接受GSE治疗的糖尿病组(每组n = 7)。GSE口服给药(100mg/kg/天),持续六周。评估以下参数:氧化应激指数、半胱天冬酶1、白细胞介素1-α、半胱天冬酶2、白细胞介素1-β、细胞死亡的BCL2相关激动剂(BAD)、X连锁凋亡抑制蛋白(XIAP)、DNA片段化因子α亚基和β亚基(DFFA、DFFB)、BH3相互作用结构域死亡激动剂(BID)、半胱天冬酶6、Bcl2样蛋白1(BCL-XL)、半胱天冬酶8、肿瘤坏死因子受体超家族成员1b(TNFRSF1B)和IAP结合线粒体蛋白(DIABLO)。

结果

与对照组相比,未治疗的糖尿病组大鼠肾脏中的氧化应激指数水平显著升高,而与未治疗的糖尿病组相比,糖尿病 + GSE组的氧化应激指数水平降低。与对照组相比,未治疗的糖尿病组大鼠肾脏中半胱天冬酶1、白细胞介素-1α、BAD、DFFA、DFFB和半胱天冬酶-6基因表达显著更高。与对照组相比,糖尿病 + GSE组中半胱天冬酶1、半胱天冬酶2、XIAP、DFFA、BID、BCL-XL和TNFRSF1B基因显著降低。

结论

葡萄籽可降低氧化应激和细胞凋亡基因表达,提示其对糖尿病肾病具有保护作用。

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