基于AMPK/ULK1信号通路探讨温阳活血化痰方对蒽环类药物心脏毒性损伤的保护机制  

Study on protective effect of Wenyang Huoxue Huatan Formula on cardiotoxic injury of anthracyclines based on AMPK/ULK1 signaling pathway

作　　者：王立玉[1] 沈雁[1] 曹玉 刘睿斯 徐婕 汪思慧 许玲[1] WANG Li-yu;SHEN Yan;CAO Yu;LIU Rui-si;XU Jie;WANG Si-hui;XU Ling(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437

出　　处：《中华中医药杂志》2022年第9期5095-5099,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.81803888)。

摘　　要：目的:观察温阳活血化痰方对阿霉素心脏毒性大鼠心脏组织腺苷酸活化蛋白激酶(AMPK)/UNC-51样激酶1(ULK1)蛋白表达的影响,研究温阳活血化痰方对阿霉素心脏毒性损伤的保护机制。方法:将SD大鼠随机分为6组,对照组,模型组,中药低、中、高剂量(温阳活血化痰方4.86、9.72、19.44 g/kg)组,奥诺先组(25 mg/kg)。采用大鼠腹腔注射阿霉素,建立阿霉素心脏毒性损伤大鼠模型,观察大鼠一般状况、心肌组织病理形态学改变,采用Western blot检测大鼠心肌组织中AMPK、pAMPK、ULK1、pULK1蛋白的表达。结果:与对照组比较,模型组大鼠心肌组织病理损害明显,心肌细胞凋亡率增多(P<0.01),大鼠心肌组织中pAMPK、pULK1表达显著增加(P<0.01)。与模型组比较,中药高、中剂量组心肌组织病理损伤不同程度减轻,凋亡率显著减少(P<0.01);pAMPK、pULK1表达降低(P<0.01,P<0.05)。结论:温阳血化痰方能有效的防治阿霉素心脏毒性损害,其作用可能与下调AMPK/ULK1信号通路,抑制心肌细胞凋亡相关。Objective: To observe the effects of Wenyang Huoxue Huatan Formula on the expression of AMPK/ULK1 protein in myocardial tissue of rats with adriamycin cardiotoxicity, and to study the protective effect of traditional Chinese medicine on cardiotoxicity damage induced by adriamycin. Methods: SD rats were randomly divided into 6 groups:the control group, model group, low-, medium-, high-dose Chinese medicine(4.86, 9.72, 19.44 g/kg) group, Onoxen group(25 mg/kg). The rat model of adriamycin cardiotoxicity was established by intraperitoneal injection of doxorubicin. The general state and pathomorphological changes of myocardial tissue of the rat were observed. Western blot was used to detect the protein expression of AMPK, pAMPK, ULK1, pULK1 in rat myocardial tissue. Results: Compared with the control group,the myocardial tissue of the model group had obvious pathological damage and more cardiomyocyte apoptosis(P<0.01), the protein expressions of pAMPK and pULK1 in the myocardial tissue of rats increased significantly(P<0.01). Compared with the model group, the pathological damage of myocardial tissue in the high-dose and medium-dose Chinese medicine groups was alleviated to different degrees, apoptotic cells were significantly reduced(P<0.01), and the expressions of pAMPK and pULK1were decreased(P<0.01, P<0.05). Conclusion: Wenyang Huoxue Huatan Formula can effectively prevent the cardiotoxic damage of adriamycin, and its effect may be related to down-regulating of AMPK/ULK1 signaling pathway and inhibiting cardiomyocyte apoptosis.

关 键 词：温阳活血化痰方 阿霉素 心脏毒性 腺苷酸活化蛋白激酶 UNC-51样激酶1 

分 类 号：R285.5[医药卫生—中药学]