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大豆源降压肽通过调节 MAPK 和 NF-κB 信号通路减轻 Ang II 诱导的肾损伤。

Soybean-derived antihypertensive hydrolysates attenuate Ang II-induced renal damage by modulating MAPK and NF-κB signaling pathways.

机构信息

School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, People's Republic of China.

Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China.

出版信息

Food Funct. 2024 Mar 4;15(5):2485-2496. doi: 10.1039/d3fo05247h.

DOI:10.1039/d3fo05247h
PMID:38334682
Abstract

Hypertension-induced kidney injury is considered a vital consequence of long-term and uncontrolled hypertension, which is commonly associated with an excessive accumulation of angiotensin II (Ang II) from hyperactivated RAS. Antihypertensive peptides have a significant effect on blood pressure regulation, but few studies have focused on the ameliorative function of antihypertensive peptides on renal injury. This study explored the effects of soybean protein-derived hydrolysate (SPH) on SHR and Ang II-induced HK-2 cells. SPH significantly attenuated blood pressure and alleviated renal pathological injury in SHRs after oral gavage administration. According to the pathological results, the kidneys of SHRs showed inflammation and SPH attenuated inflammatory cell infiltration in the kidneys of SHRs. Immunohistochemical analysis further revealed that SPH inhibited MCP-1 expression and increased Nrf2 expression in the kidneys. An HK-2 cell model demonstrated that SPH exhibited optimal activity for reducing Ang II-induced inflammatory cytokines and ROS overproduction. Mechanistically, SPH was observed to regulate MAPK/JNK and NF-κB signaling pathways. These findings indicate that potent antihypertensive SPH significantly ameliorates hypertension-induced kidney damage.

摘要

高血压引起的肾脏损伤被认为是长期和不受控制的高血压的重要后果,这通常与肾素-血管紧张素系统(RAS)过度激活导致的血管紧张素 II(Ang II)的过度积累有关。降压肽对血压调节有显著影响,但很少有研究关注降压肽对肾脏损伤的改善作用。本研究探讨了大豆蛋白水解物(SPH)对自发性高血压大鼠(SHR)和 Ang II 诱导的 HK-2 细胞的影响。SPH 通过口服灌胃给药显著降低了 SHR 的血压,并减轻了 SHR 的肾脏病理损伤。根据病理结果,SHR 的肾脏出现炎症,而 SPH 减轻了 SHR 肾脏中的炎症细胞浸润。免疫组织化学分析进一步表明,SPH 抑制了 MCP-1 的表达并增加了肾脏中 Nrf2 的表达。在 HK-2 细胞模型中,SPH 表现出降低 Ang II 诱导的炎症细胞因子和 ROS 过度产生的最佳活性。从机制上讲,SPH 被观察到调节丝裂原活化蛋白激酶(MAPK)/c-Jun N 末端激酶(JNK)和核因子-κB(NF-κB)信号通路。这些发现表明,具有强大降压作用的 SPH 可显著改善高血压引起的肾脏损伤。

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