Adrenomedullin Improves Cardiac Remodeling and Function in Obese Rats with Hypertension.

Adrenomedullin Improves Cardiac Remodeling and Function in Obese Rats with Hypertension.
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肾上腺髓质素改善肥胖高血压大鼠心脏重构和功能。

DOI:
10.3390/ph15060719
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发表时间:
2022-06-06
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
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其他
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本研究旨在探讨肾上腺髓质素(adrenomedullin,ADM,7.2 μg/kg/day,ip)对肥胖相关性高血压(obesity-related hypertension,OH)大鼠心脏重构和功能的保护作用。高脂饮食(HFD)用于诱导OH 20周。将H9 c2细胞与棕榈酸酯(PA,200 μM)孵育以模拟肥胖症中的高游离脂肪酸,用作体外模型。在OH大鼠中,ADM不仅降低体重(BW)和血压(BP),而且改善全身炎症和氧化应激。此外,ADM仍然有更大的抑制作用,局部炎症和氧化应激在OH大鼠的心脏,和相同的抗炎和抗氧化作用也证实在PA处理的H9 c2细胞。ADM受体拮抗剂或Akt抑制剂可有效减弱ADM对PA刺激的H9 c2细胞炎症和氧化应激的抑制作用。此外,ADM的应用有效地正常化心脏功能,和苏木精-伊红和Masson染色和胶原体积分数的结果表明,ADM改善心脏重构在OH大鼠的心脏。ADM通过受体-Akt通路减轻心脏炎症和氧化应激,这涉及改善OH大鼠的心脏重构和功能。
This study aimed to determine whether adrenomedullin (ADM, 7.2 μg/kg/day, ip), an important endogenous active peptide, has a protective role in cardiac remodeling and function in obesity-related hypertension (OH) rats. A high-fat diet (HFD) was used to induce OH for 20 weeks. H9c2 cells incubated with palmitate (PA, 200 μM) to mimic high free fatty acid in obesity were used as an in vitro model. In OH rats, ADM not only decreased body weight (BW) and blood pressure (BP) but also improved systemic inflammation and oxidative stress. Moreover, ADM still had a greater inhibitory effect on local inflammation and oxidative stress in the hearts of OH rats, and the same anti-inflammatory and antioxidant effects were also confirmed in PA-treated H9c2 cells. The ADM receptor antagonist or Akt inhibitor effectively attenuated the inhibitory effects of ADM on inflammation and oxidative stress in PA-stimulated H9c2 cells. Furthermore, ADM application effectively normalized heart function, and hematoxylin-eosin and Masson staining and collagen volume fraction results showed that ADM improved cardiac remodeling in hearts of OH rats. ADM attenuated cardiac inflammation and oxidative stress via the receptor-Akt pathway, which involves the improvement of cardiac remodeling and function in OH rats.
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