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血管紧张素-(1-7)通过低密度脂蛋白受体-SREBP2-SCAP途径改善高脂饮食诱导的肾损伤的抗炎作用

Anti-Inflammatory Effects of Ang-(1-7) in Ameliorating HFD-Induced Renal Injury through LDLr-SREBP2-SCAP Pathway.

作者信息

Zheng Yaning, Tang Lin, Huang Wenhan, Yan Ruyu, Ren Feifeng, Luo Lei, Zhang Ling

机构信息

Department of Nephrology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.

出版信息

PLoS One. 2015 Aug 20;10(8):e0136187. doi: 10.1371/journal.pone.0136187. eCollection 2015.

Abstract

The angiotensin converting enzyme 2-angiotensin-(1-7)-Mas axis (ACE2-Ang-(1-7)-Mas axis) is reported to participate in lipid metabolism in kidney, but its precise effects and underlying mechanisms remain unknown. We hypothesized that Ang-(1-7) reduces lipid accumulation and improves renal injury through the low density lipoprotein receptor-sterol regulatory element binding proteins 2-SREBP cleavage activating protein (LDLr-SREBP2-SCAP) system by suppressing inflammation in high fat diet (HFD)-fed mice. In this study, male C57BL/6 mice were randomized into four groups: STD (standard diet)+saline, HFD+saline, HFD+Ang-(1-7) and STD+Ang-(1-7). After 10 weeks of feeding, mice were administered Ang-(1-7) or saline for two weeks. We found that high inflammation status induced by HFD disrupted the LDLr-SREBP2-SCAP feedback system. Treatment of mice fed a high-fat diet with Ang-(1-7) induced significant improvement in inflammatory status, following the downregulation of LDLr, SREBP2 and SCAP, and then, decreased lipid deposition in kidney and improved renal injury. In conclusion, the anti-inflammatory effect of Ang-(1-7) alleviates renal injury triggered by lipid metabolic disorders through a LDLr- SREBP2-SCAP pathway.

摘要

据报道,血管紧张素转换酶2-血管紧张素-(1-7)-Mas轴(ACE2-Ang-(1-7)-Mas轴)参与肾脏脂质代谢,但其确切作用和潜在机制尚不清楚。我们推测,在高脂饮食(HFD)喂养的小鼠中,Ang-(1-7)通过低密度脂蛋白受体-固醇调节元件结合蛋白2-SREBP裂解激活蛋白(LDLr-SREBP2-SCAP)系统减少脂质积累并改善肾损伤,其机制是抑制炎症。在本研究中,雄性C57BL/6小鼠被随机分为四组:标准饮食(STD)+生理盐水组、HFD+生理盐水组、HFD+Ang-(1-7)组和STD+Ang-(1-7)组。喂养10周后,给小鼠注射Ang-(1-7)或生理盐水,持续两周。我们发现,HFD诱导的高炎症状态破坏了LDLr-SREBP2-SCAP反馈系统。用Ang-(1-7)治疗高脂饮食喂养的小鼠,可显著改善炎症状态,随后LDLr、SREBP2和SCAP下调,进而减少肾脏脂质沉积并改善肾损伤。总之,Ang-(1-7)的抗炎作用通过LDLr-SREBP2-SCAP途径减轻脂质代谢紊乱引发的肾损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e820/4546194/360a0c465248/pone.0136187.g001.jpg

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