ABSTRACT

The objective of present investigation was to appraise the effects of piperine on STZ-induced diabetic cardiomyopathy in rats. Diabetes was induced in Sprague-Dawley rats with intraperitoneal STZ injection, and the rats were assigned to seven groups. Electrocardiograph, hemodynamic, various biochemical, molecular, and histological parameters were examined. Treatment with piperine significantly (p < 0.05) restored altered myocardial functions, inhibited cardiac marker, and restored electrocardiogram and hemodynamic alterations. The elevated level of cardiac oxido-nitrosative stress and decreased cardiac Na-K-ATPase concentration, after STZ administration, were significantly (p < 0.05) attenuated by piperine treatment. Piperine also considerably (p < 0.05) increased myocardial mitochondrial enzyme activity. STZ-induced alteration in heart ANP, BNP, cTn-I, Bcl2, Bax/Bcl2, and caspase3 mRNA expression was significantly (p < 0.05) restored by piperine treatment. Piperine administration reduced histopathological aberrations induced by STZ. In conclusion, the present investigation suggests that piperine ameliorates STZ-induced diabetic cardiomyopathy via modulation of caspase-3, Bcl2, Bax/Bcl2 pathways.

Abbreviations: ACE: Angiotensin-Converting Enzyme; ANOVA: Analysis of Variance; ANP: Atrial Natriuretic Peptide; APAF: Apoptotic Protease-Activating Factor; ARB: Angiotensin Receptor Blockers; ATP: Adenosine Triphosphate; Bax: Bcl-2-associated X protein; Bcl2: B-cell lymphoma 2; BPM: Beats Per Minute; BNP: brain natriuretic peptide; CAD: Caspase-3-Activated DNase; cDNA: Complementary DNA; CK-MB: Creatine Kinase-MB; CPCSEA: Committee for the Purpose of Control And Supervision of Experiments on Animals; cTn-I: cardiac troponin I; DBP: Diastolic Blood Pressure; DCM: Diabetic Cardiomyopathy; DNA: Deoxyribonucleic Acid; DPX: DisterenePhthalate Xylene; ECG: Electrocardiogram; ETC: Electron Transport Chain; GOD-POD: Glucose Oxidase Peroxidase; GSH: Glutathione; IAEC: Institutional Animal Ethics Committee; IL-6: Interleukin-6; IL-1b: Interleukin-1b; LDH: Lactate Dehydrogenase; LV: Left Ventricle; LVEDP: left ventricular end-diastolic Pressure; MABP: Mean Arterial Blood Pressure; MDA: Malondialdehyde; mRNA: Messenger Ribonucleic Acid; MTT: 3- (4,5-Dimethylthiazol-2-yl)-2,5-DiphenyltetrazoliumBromide; NADH: Nicotinamide Adenine Dinucleotide Phosphate; NADPH: Nicotinamide Adenine Dinucleotide Phosphate Hydrogen; NO: nitric oxide; NP: Natriuretic Peptides; OXPHOS: Oxidative Phosphorylation; p.o.: per os; PCR: Polymerase Chain Reaction; RT-PCR: Reverse Transcriptionpolymerase Chain Reaction; PPAR: Peroxisome Proliferator-Activated Receptor Gamma; RAS: Renin-Angiotensin System; RNA: Ribonucleic Acid; ROS: Reactive Oxygen Species; SBP: Systolic Blood Pressure; SDH: Succinate Dehydrogenase; SEM: Standard Error Means; SOD: superoxide dismutase: STZ: Streptozotocin; TNF: Tumor Necrosis Factor Alpha; TnI: Troponin I

摘要

本研究的目的是评估胡椒碱对STZ诱导的糖尿病性心肌病的作用。腹膜内注射STZ在Sprague-Dawley大鼠中诱发糖尿病，将大鼠分为7组。检查了心电图，血流动力学，各种生化，分子和组织学参数。胡椒碱治疗可显着（p <0.05）恢复心肌功能的改变，抑制心脏标志物，并恢复心电图和血流动力学改变。服用STZ后，通过胡椒碱治疗可显着（p <0.05）减轻心脏氧化亚硝基应激水平升高和心脏Na-K-ATPase浓度降低。胡椒也相当（p<0.05）增加了心肌线粒体酶活性。胡椒碱治疗可显着恢复STZ诱导的心脏ANP，BNP，cTn-1，Bcl2，Bax / Bcl2和caspase3 mRNA表达的改变（p <0.05）。胡椒碱管理减少了由STZ诱导的组织病理学畸变。总之，本研究表明胡椒碱可通过调节caspase-3，Bcl2，Bax / Bcl2途径改善STZ诱导的糖尿病性心肌病。

缩略语ACE：血管紧张素转换酶；方差分析：方差分析；ANP：心钠素；APAF：凋亡蛋白酶激活因子；ARB：血管紧张素受体阻滞剂；ATP：三磷酸腺苷；Bax：Bcl-2相关的X蛋白；Bcl2：B细胞淋巴瘤2；BPM：每分钟节拍数；BNP：脑利钠肽；CAD：Caspase-3-激活的DNase；cDNA：互补DNA；CK-MB：肌酸激酶MB；CPCSEA：动物实验控制和监督委员会；cTn-I：心肌肌钙蛋白I；DBP：舒张压；DCM：糖尿病性心肌病；DNA：脱氧核糖核酸；DPX：邻苯二甲酸二甲苯酯二甲苯; 心电图：心电图；ETC：电子运输链；GOD-POD：葡萄糖氧化酶过氧化物酶；GSH：谷胱甘肽；IAEC：机构动物伦理委员会；IL-6：白介素-6；IL-1b：白介素-1b；LDH：乳酸脱氢酶; LV：左心室；左心室。LVEDP：左心室舒张末期压力；MABP：平均动脉血压；MDA：丙二醛；mRNA：信使核糖核酸；MTT：3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物；NADH：烟酰胺腺嘌呤二核苷酸磷酸；NADPH：烟酰胺腺嘌呤二核苷酸磷酸氢盐；NO：一氧化氮；NP：利钠肽；OXPHOS：氧化磷酸化；po：每操作系统；PCR：聚合酶链反应；RT-PCR：逆转录聚合酶链反应；PPAR：过氧化物酶体增殖物激活的受体γ；RAS：肾素-血管紧张素系统；RNA：核糖核酸；ROS：活性氧；SBP：收缩压；SDH：琥珀酸脱氢酶；SEM：标准误差平均值；SOD：超氧化物歧化酶：STZ：链脲佐菌素；TNF：肿瘤坏死因子α；TnI：