OBJECTIVE To discuss the effect and mechanism of cinepazide maleate (CM) on myocardial injured rats induced by isoproterenol (Iso). METHODS Fifty male and female rats were divided into normal group, model group, the low and the high dose group of the CM, and captopril (Cap)positive control group. The rat model of myocardial injury was established by subcutaneous injection of Iso (5 mg·kg-1·d-1)for 7 d, rats in treatment group were given intraperitoneal injection of CM on the second day (1.5,3 mg·kg-1·d-1), rats in positive control group were given intragastric administration of Cap(10 mg·kg-1·d-1), and rats in normal group and model group were given intraperitoneal injection of normal saline in the same volume, for 14 d. The rats in each group were tested before and after treatment by three times of running endurance test. After stopping drug all rats were anesthetized for measuring the electrocardiogram (ECG), then taken blood for measuring the activities of serum SOD, LDH and CK, and taken hearts for measuring heart weight index (HWI), left ventricular mass index (LHWI), the contents of myocardial hydroxyproline (Hyp)and MDA, and observing the morphological changes of myocardial tissue by HE staining. RESULTS Compared with rats in normal group, rats in model group showed endurance value decrease, ECG abnormalities (arrhythmia and myocardial ischemia in waveform), increased HWI, LHWI (P<0.01), myocardial Hyp content, myocardial MDA level, and the level of serum LDH and CK, and reduced the serum SOD activity (P<0.05 or P<0.01). Compared with model group, CM could significantly increase endurance value, improve abnormal phenomenon of ECG, lower the HWI, LHWI, myocardial Hyp content, myocardial MDA level, and serum LDH and CK levels were lower, and serum SOD activity increased, especially in high dose group of CM (P<0.01). HE staining showed in the model group rat ventricular remodeling, myocardial rupture, a large number of collagen fibers, in the treatment group, ventricular remodeling and myocardial fibrosis were significantly improved. CONCLUSION Cinepazide maleate has protective effect on myocardial injury of rats induced by Iso.
[1] TANG X H, LIU J H.Clinical application of guipaiqite[J]. Chin J Mod Drug Appl(中国现代药物应用), 2010, 4(8):223-224. [2] FU H Y. Xinbian Yiyuan Yaowu Daquan(新编医院药物大全)[M]. 2nd. Beijing:China Medical Science Press, 2003:406-407. [3] ZHAO L Z, WANG L J. Influence on neural function cerebral infarction with DI-3-budylphthalinde and cinepazidemaleate combination therapy[J]. Chin J Stroke(中国卒中杂志), 2012, 7(2):109-113. [4] HUANG K W. Cinepazide maleate combined xueshuantong treatment of vertebral-basilar artery insufficiency efficacy[J]. China Mod Doctor(中国现代医生), 2010, 48(24):103-104. [5] WANG Z P. Clinical curative effect observation of epalrestat and cinepazide maleate in the treatment of diabetic peripheral neuropathy[J]. J Clin Exp Med, 2012, 11(24):1973-1974. [6] FAN H Y, WANG Y C, REN K, et al. Inhibition of flavonoids from Sophora flavescens on myocardial fibrosis in rats[J]. Chin Tradit Herb Drugs(中草药), 2015,46(20):3055-3059. [7] LI C H, CHEN Y C, ZHAI X W, et al. Inhibitory effect of agonist of Ik1 channel on arrhythmia induced by isoproterenol in rats [J].Chin Pharmacol Bull(中国药理学通报),2015,31(8):1081-1084. [8] ZHANG W B, TANG Q S, LI J, et al. Subcutaneous injection of isopropyl adrenaline induced myocardial hypertrophy in mice model[J]. J Med Res, 2015, 44(7):88-91. [9] CHEN Y X, OU R M, ZHONG X R, et al. Granulocyte colony stimulating factor interventional experimental research for the treatment of rat myocardial infarction[J]. Chin J Pathophysiol(中国病理生理杂志), 2001, 17(12):1153-1155. [10] CAMORS E, MOBLER P, BERS D, et al. Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promotions cardiac myocyte arrhythmic activity[J]. J Mol Cell Cardiol, 2012, 52(6):1240-1248. [11] SAMUEL C, UNEMORI E, MOOKERJEE I, et al. Relax inmodulates cardiac fibroblast proliferation and collagen production and reverses cardiac fibrosis in vivo[J]. Endocrinology, 2004, 145(9):4125-4133. [12] YOUNG M. Mechanisms of mineral corticoid receptor-me-diated cardiac fibrosis and vascular inflammation[J]. Curropin Nephrol Hypertens, 2008, 17(2):174-180. [13] ZHANG Z C, YANG Y Z, CHENG H Z. Research progress of myocardial fibrosis[J]. J Clin Cardiol(临床心血管病杂志), 2004, 20(1):58-60. [14] CHEN M, FAN Z C. Cardiac weight index evaluation on the value of left cardiac insufficiency [J]. Sichuan Med J(四川医学), 2005, 26(5):483-484. [15] BULEW B, WEBER K. Cardiac fibrosis as a cause of diastolic dysfunction[J]. Herz, 2002,27(2):92-98. [16] MURPHY E, STEENBERGEN C. Mechanism underlying acute protection from cardiac ischemia-reperfusion injury[J]. Physiol Rev, 2008, 8(8):581-583. [17] KAMINAKI K, BONDA T, WOJTKOWAKA I, et al. Oxidative stress andantioxidative defense parameters early after reperfusion therapy for acute myocardial infarction[J]. Acute Card Care, 2008, 10(2):112-126. [18] XI Z C, WANG Z Y. Rosuvastatin up-regulating the expression of Sirt1/NF-κB signal pathway and inhibiting doxorubicin-induced cardiotoxicity injury in experimental mice [J]. Chin Circul J(中国循环杂志), 2014, 29(12):1029-1033.