SRC‐3 Knockout Attenuates Myocardial Injury Induced by Chronic Intermittent Hypoxia in Mice
Wanyu Wang, Hongbo Gu, Weihua Li, Yihua Lin, Xiangyang Yao, Wen Luo, Fang Lu, Shenhui Huang, Yonghong Shi, Zhengrong Huang
Abstract
This study investigated the effects of chronic intermittent hypoxia (CIH), a model of sleep apnea syndrome (SAS), on cardiac function. SRC‐3 was extremely lowly expressed in the adult mouse heart tissue, while SRC‐3 was highly expressed in the adult mouse heart tissue after CIH, suggesting that SRC‐3 is involved in CIH model. We further studied the role of SRC‐3 in CIH‐induced myocardial injury in mice. Twenty‐four healthy Balb/c male mice ( n = 16, wild type; n = 8, SRC‐3 knockout (SRC3‐KO)) were randomly divided into three groups: air control (Ctrl), CIH, and CIH+SRC3‐KO. Mice were exposed to CIH for 12 weeks. qRT‐PCR was used to evaluate cardiac expression of the following genes: 11HSD1, 11HSD2, GR, MR, COX‐2, OPN, NOX2, HIF‐1‐ α , IL‐1 β , IL‐6, iNOS, TNF‐ α , PC‐1, and TGF‐ β . Enzymatic levels of SOD, CAT, MDA, NOS, and NO in the mouse hearts were determined using commercially available kits. Immunohistochemistry (IHC) was used to evaluate NF‐ κ B expression in cardiac tissues. A transmission electron microscope (TEM) was used to evaluate myocardial ultrastructure. TUNEL staining was used to assess myocardial cell apoptosis. CIH induced cardiac damage, which was ameliorated in the SRC‐3 KO mice. CIH significantly increased the heart‐to‐body weight ratio, expression of all aforementioned genes except 11HSD1, GR, and MR, and increased the levels of MDA, NOS, NO, and NF‐ κ B, which were attenuated in the SRC‐3 KO mice. The CIH group had the lowest SOD and CAT levels, which were partially recovered in the CIH+SRC3‐KO group. 11HSD2 gene expression was elevated in both the CIH and CIH+SRC3‐KO groups compared to the Ctrl group. The CIH group had severe myocardial cell apoptosis and mitochondrial dysfunction, which were alleviated in the CIH+SRC3‐KO group. CIH causes cardiac damage through inducing oxidative stress and inflammation. Knockout of SRC‐3 ameliorates CIH‐induced cardiac damage through antagonizing CIH‐triggered molecular changes in cardiac tissue.