LCZ696通过激活Nrf2信号通路改善异丙肾上腺素诱导的大鼠急性心力衰竭

LCZ696 Ameliorates Isoproterenol-Induced Acute Heart Failure in Rats by Activating the Nrf2 Signaling Pathway.

作者信息

Hou Min, Lu Linxin, Wu Xiaobo, Liu Hongxuan

机构信息

Department of Emergency, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China.

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Appl Bionics Biomech. 2022 Apr 29;2022:6077429. doi: 10.1155/2022/6077429. eCollection 2022.

OBJECTIVE

LCZ696 (sacubitril/valsartan) is an angiotensin II (Ang II) type 1 receptor-neprilysin inhibitor, with effects of immunosuppression, anti-inflammation, antiapoptosis, and antioxidation. The present study was aimed at determining whether LCZ696 has a protective effect against isoproterenol-induced acute heart failure (AHF) in rats.

METHODS

SD rats were randomly divided into four groups: control group, HF group, LCZ696 group, and enalapril group. The cardiac function of rats was evaluated using echocardiographic parameters, heart weight (HW), serum levels of cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). HE is staining, which was used to determine the pathological damage of rat myocardial tissue. Also, we measured oxidative stress markers including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Finally, the expression of Nrf2 signaling pathway-related proteins was determined using Western blot.

RESULTS

Compared with the HF group, LCZ696 could significantly improve cardiac function and myocardial injury in rats and reduce AHF-induced oxidative stress. In addition, the results of Western blot confirmed that LCZ696 could upregulate the expression of Nrf2 and HO-1 while decreasing Keap1 expression.

CONCLUSION

LCZ696 ameliorates isoproterenol-induced AHF in rats by alleviating oxidative stress injury and activating the Nrf2 signaling pathway.

目的

LCZ696（沙库巴曲/缬沙坦）是一种血管紧张素II（Ang II）1型受体-中性肽链内切酶抑制剂，具有免疫抑制、抗炎、抗凋亡和抗氧化作用。本研究旨在确定LCZ696对异丙肾上腺素诱导的大鼠急性心力衰竭（AHF）是否具有保护作用。

方法

将SD大鼠随机分为四组：对照组、心力衰竭组、LCZ696组和依那普利组。使用超声心动图参数、心脏重量（HW）、血清心肌肌钙蛋白I（cTnI）和乳酸脱氢酶（LDH）水平评估大鼠的心功能。采用HE染色法确定大鼠心肌组织的病理损伤。此外，我们还测量了氧化应激标志物，包括活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）。最后，使用蛋白质印迹法测定Nrf2信号通路相关蛋白的表达。