Department of Cardiology, 519688Yantaishan Hospital, Affiliated to Binzhou Medical University, Yantai City, China.
Department of Cardiology, 91589Gansu Provincial Hospital, Lanzhou, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221077684. doi: 10.1177/09603271221077684.
Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A receptor (AR) in rats with myocardial ischemia-reperfusion (MI/R).
Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the AR agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + AR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of AR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured.
Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased ( < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between AR and collagen I and collagen III was found ( = 0.00).
SFI activated the AR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.
参附注射液（SFI）在中国常用于心脏功能障碍。已有研究报道，腺苷受体具有抗纤维化作用。本研究旨在评估 SFI 通过激活心肌缺血再灌注（MI/R）大鼠的腺苷 A 受体（AR）来减轻心脏纤维化。
将雄性 Sprague Dawley 大鼠随机分为五组，每组 9 只。所有大鼠组均在再灌注前进行注射，假手术和 MI/R 组仅注射载体。其余组的注射情况如下：SFI 组 5 mL/kg；AR 激动剂组 15 mg/kg 尼可地尔；SFI+AR 拮抗剂组 5 mL/kg 加 5 mg/kg MSX-3。记录各组环磷酸腺苷（cAMP）的变化以及心肌梗死和心肌纤维化的发展情况。此外，还测量了 AR、胶原 Ⅰ、胶原 Ⅲ、纤维连接蛋白和基质金属蛋白酶-9（MMP-9）的水平。
SFI 或尼可地尔注射后，MI/R 损伤引起的 cAMP 浓度、梗死面积和心肌纤维化明显减少（<0.05）。此外，与 MI/R 组相比，SFI 或尼可地尔明显抑制了胶原 Ⅰ、胶原 Ⅲ、纤维连接蛋白和 MMP-9 的水平（<0.01）。然而，SFI 的保护作用被 MSX-3 抵消。AR 与胶原 I 和胶原 III 呈负相关（=0.00）。
SFI 激活 AR 减少 MI/R 损伤引起的心肌纤维化，为 SFI 的作用机制提供了依据。
