a Department of Pharmacology, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
b Department of Pharmacology (Ilmul Advia), Ajmal Khan Tibbiya College , Aligarh Muslim University , Uttar Pradesh , India.
Clin Exp Hypertens. 2019;41(1):62-69. doi: 10.1080/10641963.2018.1441862. Epub 2018 Mar 29.
Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin.
The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL).
Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI.
Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.
沙库比曲（SAC）是一种脑啡肽酶抑制剂，可防止脑啡肽酶降解，并通过血管活性肽、肾上腺髓质素和缓激肽激活 cGMP 信号通路，导致血容量增加，同时血压升高。
本研究旨在通过抑制异丙肾上腺素（ISO）诱导的 Wistar 白化大鼠心肌梗死（MI）中的 Neprilysin 来评估 SAC 的抗缺血作用。ISO（85mg/kg）在 SAC 和缬沙坦（VAL）预处理 14 天后皮下注射。
生化研究表明，SAC 与 VAL 一起可显著防止 ISO 中毒引起的 Wistar 大鼠抗氧化酶（SOD、Catalase、GR、GPx、GST 和 GSH）降解和丙二醛（MDA）增加。除此之外，SAC 和 VAL 还可显著改善 ISO 处理大鼠的心脏生物标志物（LDH、CK-MB、ALT、AST 和 ALP）。同时，SAC 和 VAL 降低了梗死面积（IA），并显著减轻了肌原纤维损伤，进一步支持了其在 MI 中的保护作用。
综上所述，这些结果表明，抑制酶 Neprilysin 可减轻 ISO 诱导的心肌损伤，其强大的抗氧化潜力是其作用机制之一。
