12 February 2020 : Animal Research
Deficiency of Interleukin-36 Receptor Protected Cardiomyocytes from Ischemia-Reperfusion Injury in Cardiopulmonary BypassCheng Luo1ABDE, Xiaoyong Xie1ABDE, Xu Feng1CD, Binfeng Lei1EFG, Chen Fang1CF, Yugui Li1CDE, Xiongwei Cai1AD, Guoxing Ling1BCE, Baoshi Zheng1ABE*
Med Sci Monit 2020; 26:e918933
BACKGROUND: Interleukin-36 has been demonstrated to be involved in inflammatory responses. Inflammatory responses due to ischemia-reperfusion injury following cardiopulmonary bypass (CPB) can cause heart dysfunction or damage.
MATERIAL AND METHODS: The CPB models were constructed in IL-36R–/–, IL-36RN–/–, and wild-type SD rats. Ultrasonic cardiography and ELISA were used to evaluate the cardiac function and measuring myocardial biomarker levels in different groups. TUNEL assay was used to evaluate apoptosis. Western blot assays and RT-PCR were performed to measure the expression of chemokines and secondary inflammatory cytokines in the heart. Oxidative stress in tissue and cultured cells was assessed using a DCFH-DA fluorescence probe and quantification of superoxide dismutase activity.
RESULTS: Improved systolic function and decreased serum levels of myocardial damage biomarkers were found in IL-36R–/– rats compared to WT rats, while worse cardiac function and cardiomyocyte IR injury were observed in IL-36RN–/– rats compared to WT rats. TUNEL staining and Western blot analyses found that cardiomyocyte apoptosis and inflammation were significantly lower in the hearts of IL-36R–/– rats compared with that of WT rats. Oxidative stress was significantly lower in IL-36R–/– rats compared to WT rats. iNOS expression was significantly reduced, while eNOS expression was increased in the hearts of IL-36R–/– rats. Silencing of IL-36R expression in vitro activated SIRT1/FOXO1/p53 signaling in cardiomyocytes.
CONCLUSIONS: IL-36R deficiency in cardiomyocytes repressed infiltration of bone marrow-derived inflammatory cells and oxidative stress dependent on SIRT1-FOXO1 signaling, thus protecting cardiomyocytes and improving cardiac function in CPB model rats.
Keywords: Interleukin-11 Receptor alpha Subunit, Interleukin-3 Receptor alpha Subunit, Interleukin-4 Receptor alpha Subunit, Cardiopulmonary Bypass, Gene Knockout Techniques, Myocardial Reperfusion Injury, Myocardium, Myocytes, Cardiac, Nerve Tissue Proteins, Oxidative Stress, Rats, Transgenic, Receptors, Interleukin, Signal Transduction, Sirtuin 1
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