Shen Shutong, Jiang Huimin, Bei Yihua, Zhang Jialiang, Zhang Haifeng, Zhu Hongsheng, Zhang Chenlin, Yao Wenming, Wei Cong, Shang Hongcai, Li Xinli
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Clinical Laboratory Center, Beijing Hospital of Traditional Chinese Medicine, Beijing, China.
Cell Physiol Biochem. 2017;42(3):876-888. doi: 10.1159/000478641. Epub 2017 Jun 23.
BACKGROUND/AIMS: This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice.
Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice. Masson's Trichrome staining was applied to evaluate myocardial fibrosis. Collagen deposition was determined by the mRNA level of Collagen I, Collagen III and α-SMA using real-time quantitative polymerase chain reaction (qPCR). Myocardial apoptosis was examined by the protein level of Bax, Bcl2 and the Bcl2/Bax ratio using western blotting.
These mice displayed a significant reduction in heart function, increased myocardial fibrosis and apoptosis, and decreased expression of peroxisome proliferator activated receptor γ (PPARγ) in the heart tissue, which could be reversed by QLQX treatment. Inhibition of PPAR reduced QLQX-mediated cardio-protective effects, while PPARγ activation did not further enhance the beneficial effect of QLQX. Furthermore, QLQX upregulated 9 genes (Cd36, Fatp, Pdk4, Acadm, Acadl, Acadvl, Cpt1a, Cpt1b and Cpt2) facilitating energy metabolism in the MI hearts of the OVX mice and 5 (Acadm, Acadl, Cpt1a, Cpt1b, Cpt2) of the 9 genes were the downstream targets of PPARγ.
The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPARγ, suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.
背景/目的：本研究旨在探讨中药芪苈强心（QLQX）对双侧卵巢切除（OVX）雌性小鼠心肌梗死后不良心脏重塑的治疗作用。
8周龄雌性C57BL/6小鼠在双侧卵巢切除术后7天进行左冠状动脉前降支结扎手术，并口服给予QLQX或赋形剂。结扎后21天，进行超声心动图检查以评估所有小鼠的心脏功能。采用Masson三色染色法评估心肌纤维化。使用实时定量聚合酶链反应（qPCR）通过I型胶原、III型胶原和α -平滑肌肌动蛋白（α - SMA）的mRNA水平测定胶原沉积。通过蛋白质印迹法检测Bax、Bcl2蛋白水平及Bcl2/Bax比值来检测心肌细胞凋亡。
这些小鼠心脏功能显著降低，心肌纤维化和凋亡增加，心脏组织中过氧化物酶体增殖物激活受体γ（PPARγ）表达降低，而QLQX治疗可使其逆转。抑制PPAR可降低QLQX介导的心脏保护作用，而激活PPARγ并未进一步增强QLQX的有益作用。此外，QLQX上调了9个促进OVX小鼠心肌梗死心脏能量代谢的基因（Cd36、脂肪酸转运蛋白（Fatp）、丙酮酸脱氢酶激酶4（Pdk4）、肉碱/有机阳离子转运体2（OCTN2）、肉碱/有机阳离子转运体1（OCTN1）、长链脂酰辅酶A脱氢酶（ACADL）、长链3 - 羟酰基辅酶A脱氢酶（HADH）、肉碱棕榈酰转移酶1A（Cpt1a）、肉碱棕榈酰转移酶1B（Cpt1b）和肉碱棕榈酰转移酶2（Cpt2）），其中9个基因中的5个（OCTN2、OCTN1、ACADL、Cpt1a、Cpt1b）是PPARγ的下游靶点。
本研究表明，QLQX通过激活PPARγ对双侧OVX雌性小鼠心肌梗死后的病理重塑具有治疗作用，提示QLQX可能是治疗绝经后心肌梗死女性的一种有前景的药物。
