心肌缺血严重威胁人体健康，其主要病因是血管功能障碍。补虚通瘀颗粒（BXTY）是治疗心肌缺血的有效中药。然而，BXTY发挥抗心肌缺血作用的潜在机制尚不清楚。在这项研究中，我们证明了BXTY通过激活血管平滑肌细胞（VSMCs）中的可溶性鸟苷酸环化酶（sGC）-3′,5′-环鸟苷单磷酸（cGMP）-蛋白激酶G（PKG）信号通路扩张动脉血管，改善心肌缺血。本研究中，我们使用昆明小鼠连续灌胃BXTY 10 d后，腹腔注射垂体后叶素建立小鼠急性心肌缺血动物模型。结果显示，BXTY能减轻垂体后叶素所致小鼠心肌缺血症状，包括心电图异常和血浆酶的改变。此外，BXTY舒张预收缩的肠系膜上动脉血管，抑制肠系膜上动脉血管收缩，且这两种作用均呈剂量依赖性，但不具内皮依赖性。使用sGC抑制剂NS 2028/ODQ、PKG抑制剂KT 5823处理血管可以抑制BXTY对血管舒缩的影响。此外，在小鼠主动脉血管平滑肌细胞（MOVAs）中，BXTY增加sGC-β₁蛋白表达及细胞内第二信使cGMP水平，NS 2028/ODQ逆转了这些现象。BXTY孵育MOVAs后，cGMP下游效应蛋白PKG-1表达水平升高，然而，NS 2028/ODQ或KT 5823处理细胞能部分逆转BXTY对sGC-β₁、cGMP和PKG-1水平的影响。综上所述，BXTY通过激活VSMCs中sGC-cGMP-PKG通路诱导血管舒张改善小鼠急性心肌缺血症状。

Myocardial ischemia is a serious threat to human health, and vascular dysfunction is its main cause. Buxu Tongyu (BXTY) Granule is an effective traditional Chinese medicine (TCM) for treating myocardial ischemia. However, the underlying mechanism of BXTY is still unclear. In this study, we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase (sGC)-3′,5′-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin. The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice, including electrocardiogram abnormalities and changes in plasma enzymes. In addition, BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner. These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ, or with the PKG inhibitor KT 5823. Moreover, BXTY increased the protein expression of sGC-β₁ and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells (MOVAs). NS 2028 or ODQ reversed these effects of BXTY. The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY. NS 2028, ODQ, or KT 5823 also reversed this effect of BXTY. In conclusion, BXTY can improve the symptoms of acute myocardial ischemia in mice, and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.