Yan Lu-Lu, Zhang Wei-Yang, Wei Xiao-Hong, Yan Li, Pan Chun-Shui, Yu Yang, Fan Jing-Yu, Liu Yu-Ying, Zhou Hua, Han Jing-Yan, Yao Xin-Sheng
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Front Physiol. 2018 Apr 4;9:296. doi: 10.3389/fphys.2018.00296. eCollection 2018.
Gualou Xiebai Decoction (GLXB) is a classic prescription of Chinese medicine used for the treatment of cardiac problems. The present study was designed to explore the effect and mechanism of GLXB on ischemia/reperfusion (I/R) induced disorders in myocardial structure and function, focusing on the regulation of energy metabolism and the RhoA/ROCK pathway. After hyperlipidemic rat model was established by oral administration of high fat diet, the rats were treated with GLXB for 6 weeks and subjected to 30 min occlusion of the left anterior descending coronary artery (LADCA) followed by 90 min reperfusion to elicit I/R challenge. Myocardial infarct size was assessed by Evans blue-TTC staining. Myocardial blood flow (MBF) and cardiac function were evaluated. Enzyme-linked immunosorbent assay was performed to examine the content of ATP, ADP, AMP, CK, CK-MB, LDH, cTnT, cTnI, and IL-6. Double staining of F-actin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was conducted to assess myocardial apoptosis. Expressions of ATP synthase subunit δ (ATP 5D), and RhoA and ROCK were determined by Western blotting. Administration with GLXB at high dose for 6 weeks protected heart against I/R-induced MBF decrease, myocardial infarction and apoptosis, ameliorated I/R-caused impairment of cardiac function and myocardial structure, restored the decrease in the ratio of ADP/ATP and AMP/ATP, and the expression of ATP 5D with inhibiting the expression of RhoA and ROCK. Treatment with GLXB effectively protects myocardial structure and function from I/R challenge, possibly via regulating energy metabolism involving inactivation of RhoA/ROCK signaling pathway.
瓜蒌薤白汤(GLXB)是一种用于治疗心脏问题的经典中药方剂。本研究旨在探讨瓜蒌薤白汤对缺血/再灌注(I/R)诱导的心肌结构和功能紊乱的影响及机制,重点关注能量代谢调节和RhoA/ROCK信号通路。通过口服高脂饮食建立高脂血症大鼠模型后,给予大鼠瓜蒌薤白汤治疗6周,然后结扎左冠状动脉前降支(LADCA)30分钟,再灌注90分钟以引发I/R损伤。通过伊文思蓝-氯化三苯基四氮唑(Evans blue-TTC)染色评估心肌梗死面积。评估心肌血流量(MBF)和心脏功能。采用酶联免疫吸附测定法检测ATP、ADP、AMP、肌酸激酶(CK)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白T(cTnT)、心肌肌钙蛋白I(cTnI)和白细胞介素-6(IL-6)的含量。进行F-肌动蛋白和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记双重染色以评估心肌细胞凋亡。通过蛋白质免疫印迹法测定ATP合酶亚基δ(ATP 5D)、RhoA和ROCK的表达。高剂量瓜蒌薤白汤给药6周可保护心脏免受I/R诱导的MBF降低、心肌梗死和细胞凋亡,改善I/R引起的心脏功能和心肌结构损伤,恢复ADP/ATP和AMP/ATP比值的降低以及ATP 5D的表达,并抑制RhoA和ROCK的表达。瓜蒌薤白汤治疗可有效保护心肌结构和功能免受I/R损伤,可能是通过调节能量代谢,包括使RhoA/ROCK信号通路失活来实现的。