Wang Feng, Wang Lixin, Jiao Yue, Wang Zhirong
Hebei University of Chinese Medicine, Shijiazhuang, China.
Hebei University of Chinese Medicine, Shijiazhuang, China; Department of Cardiovascular Disease, Hebei Province Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou, China.
Ann Palliat Med. 2020 Sep;9(5):3453-3461. doi: 10.21037/apm-20-1746.
One of the common adverse reactions to anthracyclines, a group of chemotherapeutics, is cardiotoxicity. Cancer patients receiving anthracycline-based chemotherapeutic regimens often discontinue treatment due to cardiotoxicity. How to prevent and reduce the cardiotoxicity of anthracyclines is one of the hot topics in the field of onco-cardiology. Traditional Chinese medicine can reduce the toxic side effects of chemotherapeutics. The present study aimed to investigate the protective effect of Qishen Huanwu capsule (QSHWC) on pirarubicin (THP)-induced myocardial injury in rats and the underlying mechanisms.
Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six groups: control group, THP, low-dose QSHWC, moderate-dose QSHWC, high-dose QSHWC, and LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] (n=8 each). Echocardiographic examination was performed to examine heart structure and function. Hematoxylin and eosin (HE) staining was conducted to examine histopathological changes in myocardial tissue. Immunofluorescence staining was carried out to examine the expression of the autophagosome-specific marker protein microtubule-associated protein 1 light chain 3 (LC3). Western blot was performed to analyze the expression of LC3-I, LC3-II, PI3K, phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR.
Compared with the control group, the THP group had a higher left ventricular end-systolic diameter (LVESD), lower left ventricular ejection fraction (LVEF), lower left ventricular fractional shortening (LVFS), and inferior heart function. In addition, compared with the control group, the THP group had significantly higher LC3 protein expression, a significantly higher LC3-II/LC3-I ratio (P<0.05), and significantly lower p-PI3K, p-Akt, and p-mTOR (P<0.05). QSHWC attenuated the THP-induced decline in heart function, downregulated LC3 protein in rat myocardial tissue, decreased the LC3-II/LC3-I ratio, and increased p-PI3K, p-Akt, and p-mTOR. In the LY294002 group, the above effects of QSHWC were reversed.
QSHWC alleviated THP-induced myocardial injury. The underlying mechanism was related to the activation of the PI3K/Akt/mTOR pathway and the mitigation of the excessive autophagy of cardiomyocytes caused by THP.
蒽环类药物是一类化疗药物，其常见的不良反应之一是心脏毒性。接受基于蒽环类药物化疗方案的癌症患者常因心脏毒性而中断治疗。如何预防和降低蒽环类药物的心脏毒性是肿瘤心脏病学领域的热点话题之一。中药可以减轻化疗药物的毒副作用。本研究旨在探讨芪参环乌胶囊（QSHWC）对吡柔比星（THP）诱导的大鼠心肌损伤的保护作用及其潜在机制。
将48只雄性Sprague-Dawley（SD）大鼠随机分为6组：对照组、THP组、低剂量QSHWC组、中剂量QSHWC组、高剂量QSHWC组和LY294002[磷脂酰肌醇3激酶（PI3K）抑制剂]组（每组n = 8）。进行超声心动图检查以检测心脏结构和功能。进行苏木精-伊红（HE）染色以检测心肌组织的组织病理学变化。进行免疫荧光染色以检测自噬体特异性标记蛋白微管相关蛋白1轻链3（LC3）的表达。进行蛋白质免疫印迹法分析LC3-I、LC3-II、PI3K、磷酸化（p）-PI3K、蛋白激酶B（Akt）、p-Akt、哺乳动物雷帕霉素靶蛋白（mTOR）和p-mTOR的表达。
与对照组相比，THP组左心室收缩末期内径（LVESD）更高，左心室射血分数（LVEF）更低，左心室短轴缩短率（LVFS）更低，心脏功能较差。此外，与对照组相比，THP组LC3蛋白表达显著更高，LC3-II/LC3-I比值显著更高（P<0.05），p-PI3K、p-Akt和p-mTOR显著更低（P<0.05）。QSHWC减轻了THP诱导的心脏功能下降，下调了大鼠心肌组织中的LC3蛋白，降低了LC3-II/LC3-I比值，并增加了p-PI3K、p-Akt和p-mTOR。在LY294002组中，QSHWC的上述作用被逆转。
QSHWC减轻了THP诱导的心肌损伤。其潜在机制与PI3K/Akt/mTOR通路的激活以及THP引起的心肌细胞过度自噬的减轻有关。
