Tissue kallikrein-related peptidase8 protects rat heart against acute ischemia reperfusion injury
Tissue kallikrein-related peptidase8 protects rat heart against acute ischemia reperfusion injury
复制标题
组织激肽释放酶相关肽酶8保护大鼠心脏免受急性缺血再灌注损伤
DOI：
10.1016/j.ijbiomac.2019.08.195
复制
发表时间：
2019-11-01
影响因子：
8.2
通讯作者：
Cong, Binhai
中科院分区：
文献类型：
--
作者：
Huang, Meineng;Du, Jiankui;Cong, Binhai
组织钾化肽相关肽酶（KLKs）在急性心脏损伤和心脏重构中起重要作用。然而，KLK8对心脏的确切作用尚未确定。建立过表达KLK8的转基因大鼠，研究KLK8在心脏中的作用。缺血再灌注（I/R）诱导心肌损伤，梗死面积测定和TUNEL染色检测。在培养的新生大鼠心肌细胞（CMs）中研究其分子机制。Western blot检测蛋白水平。心肌缺血危险区KLK8蛋白水平显著升高。KLK8过表达减轻了I/ r诱导的心脏损伤，这可以通过降低心肌缺血危险区域的梗死面积和细胞凋亡来证明。体外研究发现，KLK8过表达可减轻cm的缺氧/再氧化（H/R）损伤；B2R和PAR2拮抗剂均能显著减弱kix8诱导的H/R损伤下的保护作用。此外，KLK8过表达的CMs在H/R刺激下，Akt、ERK1/2和PKA的磷酸化水平显著升高；B2R拮抗剂可降低Akt和ERK1/2的磷酸化水平，而PAR2拮抗剂可降低PKA和ERK1/2的磷酸化水平。KLK8对1/ r诱导的心脏损伤具有保护作用，可能成为心脏医学新的治疗靶点。(C) 2019 Elsevier B.V.版权所有
Tissue kallikrein-related peptidases (KLKs) play important roles in acute cardiac injury and cardiac remodeling. However, the exact cardiac actions of KLK8 have not been determined.Transgenic rat overexpressing KLK8 was established to examine the role of KLK8 in the heart. Cardiac injury was induced by ischemia/reperfusion (I/R) and examined by infarct size measurement and TUNEL staining. The molecular mechanisms were investigated in cultured neonatal rat cardiomyocytes (CMs). Western blot analysis was used to determine the protein levels.KLK8 protein level was significantly increased in the cardiac ischemic risk area. KLK8 overexpression mitigated I/R-induced cardiac injury, as evidenced by decreased infarct size and apoptosis in cardiac ischemic risk area in vivo. Via in vitro studies, it was found that KLK8 overexpression attenuated the Hypoxia/Reoxygenation (H/R) injury in CMs; both B2R and PAR2 antagonist significantly attenuated KIX8-induced protective actions under H/R injury. Moreover, KLK8 overexpressed CMs showed significant higher phosphorylation levels of Akt, ERK1/2 and PKA under H/R stimulation; B2R antagonist attenuated the phosphorylation levels of Akt and ERK1/2, while PAR2 antagonist attenuated the phosphorylation levels of PKA and ERK1/2.KLK8 protects the heart against 1/R-induced cardiac injury, which may represent a new therapeutic target in cardiac medicine. (C) 2019 Elsevier B.V. All rights reserved.