Abstract：
OBJECTIVE: Myocardial injuries resulting from hypoxia are a significant concern, and this study aimed to explore potential protective strategies against such damage. Specifically, we sought to investigate the cardioprotective effects of 16α-hydroxyestrone (16α-OHE1).
METHODS: Male Sprague‒Dawley (SD) rats were subjected to hypoxic conditions simulating high-altitude exposure at 6000 m in a low-pressure chamber for 7 days. Before and during hypoxic exposure, estradiol (E2) and various doses of 16α-OHE1 were administered for 14 days. Heart weight/body weight (HW/BW), myocardial structure, Myocardial injury indicators and inflammatory infiltration in rats were measured. H9C2 cells cultured under 5% O2 conditions received E2 and varying doses of 16α-OHE1; Cell viability, apoptosis, inflammatory infiltration, and Myocardial injury indicators were determined. Expression levels of β2AR were determined in rat hearts and H9C2 cells. The β2AR inhibitor, ICI 118,551, was employed to investigate β2AR\'s role in 16α-OHE1\'s cardioprotective effects.
RESULTS: Hypoxia led to substantial myocardial damage, evident in increased heart HW, CK-MB, cTnT, ANP, BNP, structural myocardial changes, inflammatory infiltration, and apoptosis. Pre-treatment with E2 and 16α-OHE1 significantly mitigated these adverse changes. Importantly, the protective effects of E2 and 16α-OHE1 were associated with the upregulation of β2AR expression in both rat hearts and H9C2 cells. However, inhibition of β2AR by ICI 118,551 in H9C2 cells nullified the protective effect of 16α-OHE1 on myocardium.
CONCLUSIONS: Our findings suggest that 16α-OHE1 can effectively reduce hypoxia-induced myocardial injury in rats through β2ARs, indicating a promising avenue for cardioprotection.
METHODS: Male Sprague‒Dawley (SD) rats were subjected to hypoxic conditions simulating high-altitude exposure at 6000 m in a low-pressure chamber for 7 days. Before and during hypoxic exposure, estradiol (E2) and various doses of 16α-OHE1 were administered for 14 days. Heart weight/body weight (HW/BW), myocardial structure, Myocardial injury indicators and inflammatory infiltration in rats were measured. H9C2 cells cultured under 5% O2 conditions received E2 and varying doses of 16α-OHE1; Cell viability, apoptosis, inflammatory infiltration, and Myocardial injury indicators were determined. Expression levels of β2AR were determined in rat hearts and H9C2 cells. The β2AR inhibitor, ICI 118,551, was employed to investigate β2AR\'s role in 16α-OHE1\'s cardioprotective effects.
RESULTS: Hypoxia led to substantial myocardial damage, evident in increased heart HW, CK-MB, cTnT, ANP, BNP, structural myocardial changes, inflammatory infiltration, and apoptosis. Pre-treatment with E2 and 16α-OHE1 significantly mitigated these adverse changes. Importantly, the protective effects of E2 and 16α-OHE1 were associated with the upregulation of β2AR expression in both rat hearts and H9C2 cells. However, inhibition of β2AR by ICI 118,551 in H9C2 cells nullified the protective effect of 16α-OHE1 on myocardium.
CONCLUSIONS: Our findings suggest that 16α-OHE1 can effectively reduce hypoxia-induced myocardial injury in rats through β2ARs, indicating a promising avenue for cardioprotection.
摘要：
目的：缺氧引起的心肌损伤是一个重要的问题，这项研究旨在探索针对这种损害的潜在保护策略。具体来说,我们试图研究16α-羟基雌酮(16α-OHE1)的心脏保护作用.
方法：雄性Sprague-Dawley（SD）大鼠在低压室中经历模拟6000m高空暴露的低氧条件7天。在低氧暴露之前和期间，雌二醇（E2）和各种剂量的16α-OHE1给药14天。心脏重量/体重（HW/BW），心肌结构，测定大鼠心肌损伤指标及炎症浸润。在5％O2条件下培养的H9C2细胞接受E2和不同剂量的16α-OHE1;细胞活力，凋亡，炎性浸润,并测定心肌损伤指标。测定β2AR在大鼠心脏和H9C2细胞中的表达水平。β2AR抑制剂，ICI118,551用于研究β2AR在16α-OHE1心脏保护作用中的作用。
结果：缺氧导致实质性心肌损伤，在心脏HW增加中很明显，CK-MB,cTnT,ANP,BNP,心肌结构改变,炎性浸润,和凋亡。用E2和16α-OHE1预处理显著减轻了这些不利变化。重要的是,E2和16α-OHE1的保护作用与大鼠心脏和H9C2细胞中β2AR表达的上调有关。然而,ICI118,551对H9C2细胞中β2AR的抑制作用使16α-OHE1对心肌的保护作用无效。
结论：我们的发现表明16α-OHE1可以通过β2ARs有效减轻缺氧诱导的大鼠心肌损伤，表明了一个有希望的心脏保护途径。
方法：雄性Sprague-Dawley（SD）大鼠在低压室中经历模拟6000m高空暴露的低氧条件7天。在低氧暴露之前和期间，雌二醇（E2）和各种剂量的16α-OHE1给药14天。心脏重量/体重（HW/BW），心肌结构，测定大鼠心肌损伤指标及炎症浸润。在5％O2条件下培养的H9C2细胞接受E2和不同剂量的16α-OHE1;细胞活力，凋亡，炎性浸润,并测定心肌损伤指标。测定β2AR在大鼠心脏和H9C2细胞中的表达水平。β2AR抑制剂，ICI118,551用于研究β2AR在16α-OHE1心脏保护作用中的作用。
结果：缺氧导致实质性心肌损伤，在心脏HW增加中很明显，CK-MB,cTnT,ANP,BNP,心肌结构改变,炎性浸润,和凋亡。用E2和16α-OHE1预处理显著减轻了这些不利变化。重要的是,E2和16α-OHE1的保护作用与大鼠心脏和H9C2细胞中β2AR表达的上调有关。然而,ICI118,551对H9C2细胞中β2AR的抑制作用使16α-OHE1对心肌的保护作用无效。
结论：我们的发现表明16α-OHE1可以通过β2ARs有效减轻缺氧诱导的大鼠心肌损伤，表明了一个有希望的心脏保护途径。
