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稻米糠醇浓缩物通过下调 SREBP1 而非β-氧化降低糖尿病肾病的降脂和抗氧化作用。

Hypolipidemic and Antioxidant Properties of Oryzanol Concentrate in Reducing Diabetic Nephropathy via SREBP1 Downregulation Rather than β-Oxidation.

机构信息

Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.

出版信息

Mol Nutr Food Res. 2018 Apr;62(8):e1700511. doi: 10.1002/mnfr.201700511. Epub 2018 Apr 3.

DOI:10.1002/mnfr.201700511
PMID:29469229
Abstract

SCOPE

Diabetic nephropathy (DN) is a micro-vascular complication of chronic diabetes. Sterol regulatory element binding protein1 (SREBP1) participation in the development of DN is reported. Oryzanol concentrate (OC) at 0.1% and 0.3% is tested for its antioxidant and hypolipidemic effects. The aim of the work is to study the involvement of OC in the amelioration of DN in STZ-induced diabetic animal model.

METHODS AND RESULTS

Animals were grouped into starch, high-fat, and OC-treated control/diabetic groups (SFC/SFD, HFC/HFD, OFC/OFD). The markers of DN, increased glomerular filtration rate and kidney weight, were evident in HFD and reduced in OFD group by ≈1.09 and ≈1.3 fold, respectively. The amelioration of defensive antioxidant enzyme activities and lipid peroxidation, expressions of lipid-associated biomolecules (SREBP1 and FAS) were also observed. HFD showed increased ECM accumulation of glycoproteins, particularly Type IV collagen, fibronectin. SREBP1-associated gene transforming growth factor-β (TGF-β) was reduced on treatment (OFD ≈ 1.3 fold) as to HFD (≈2.7 fold).

CONCLUSION

Oryzanol concentrate, having hypolipidemic and antioxidant properties, also downregulated the lipid biosynthesis through reduced SREBP1-TGF-β interactions (EMSA) and could effectively ameliorate DN. Gene (ACC2, Cpt1, and ACOX) expression studies showed that β-oxidation was not involved in reducing DN.

摘要

范围

糖尿病肾病(DN)是慢性糖尿病的一种微血管并发症。有报道称固醇调节元件结合蛋白 1(SREBP1)参与了 DN 的发生。稻糠甾醇浓缩物(OC)以 0.1%和 0.3%的浓度进行了抗氧化和降血脂作用的测试。本工作的目的是研究 OC 在改善 STZ 诱导的糖尿病动物模型中 DN 中的作用。

方法和结果

动物被分为淀粉、高脂肪和 OC 处理的对照组/糖尿病组(SFC/SFD、HFC/HFD、OFC/OFD)。在 HFD 组中,DN 的标志物,即肾小球滤过率和肾脏重量的增加,分别明显增加了≈1.09 和≈1.3 倍,而在 OFD 组中则降低了≈1.09 和≈1.3 倍。防御性抗氧化酶活性和脂质过氧化作用的改善,以及脂质相关生物分子(SREBP1 和 FAS)的表达也得到了观察。HFD 显示糖蛋白(特别是 IV 型胶原蛋白、纤维连接蛋白)的细胞外基质(ECM)积累增加。SREBP1 相关基因转化生长因子-β(TGF-β)在治疗后(OFD≈1.3 倍)减少,而在 HFD 组(≈2.7 倍)则减少。

结论

稻糠甾醇浓缩物具有降血脂和抗氧化作用,还通过减少 SREBP1-TGF-β 相互作用(EMSA)下调脂质生物合成,可有效改善 DN。基因(ACC2、CPT1 和 ACOX)表达研究表明,β-氧化不参与降低 DN。

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