Department of Physiology, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria; Department of Physiology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria.
Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, University of Ibadan, Nigeria.
Microvasc Res. 2024 Sep;155:104710. doi: 10.1016/j.mvr.2024.104710. Epub 2024 Jun 14.
Vincristine (VCR), a vinca alkaloid with anti-tumor and anti-oxidant properties, is acclaimed to possess cardioprotective action. However, the molecular mechanism underlying this protective effect remains unknown. This study investigated the effects of VCR on isoprenaline (ISO), a beta-adrenergic receptor agonist, induced cardiac hypertrophy in male Wistar rats. Animals were pre-treated with ISO (1 mg/kg) intraperitoneally for 14 days before VCR (25 μg/kg) intraperitoneal injection from days 1 to 28. Thereafter, mechanical, and electrical activities of the hearts of the rats were measured using a non-invasive blood pressure monitor and an electrocardiograph, respectively. After which, the heart was homogenized, and supernatants were assayed for contractile proteins: endothelin-1, cardiac troponin-1, angiotensin-II, and creatine kinase-MB, with markers of oxidative/nitrergic stress (SOD, CAT, MDA, GSH, and NO), inflammation (TNF-a and IL-6, NF-kB), and caspase-3 indicative of VCR reduced elevated blood pressure and reversed the abnormal electrocardiogram. ISO-induced increased endothelin-1, cardiac troponin-1, angiotensin-II, and creatine phosphokinase-MB, which were reversed by VCR. ISO also increased TNF-α, IL-6, NF-kB expression with increased caspase-3-mediated apoptosis in the heart. However, VCR reduced ISO-induced inflammation and apoptosis, with improved endogenous antioxidant agents (GSH, SOD, CAT) relative to ISO controls. Moreso, VCR, protected against ISO-induced histoarchitectural degeneration of cardiac myofibre. The result of this study revealed that VCR treatment significantly reverses ISO-induced cardiac hypertrophic phenotypes, via mechanisms connected to improved levels of proteins involved in excitation-contraction, and suppression of oxido-inflammatory and apoptotic pathways.
长春新碱（VCR）是一种具有抗肿瘤和抗氧化特性的长春花生物碱，据称具有心脏保护作用。然而，这种保护作用的分子机制尚不清楚。本研究探讨了长春新碱（VCR）对异丙肾上腺素（ISO）的影响，ISO 是一种β-肾上腺素能受体激动剂，可诱导雄性 Wistar 大鼠心脏肥大。动物在 VCR（25μg/kg）腹腔注射的第 1 至 28 天期间，每天预先用 ISO（1mg/kg）腹腔注射 14 天。此后，使用非侵入性血压监测仪和心电图仪分别测量大鼠心脏的机械和电活动。然后，将心脏匀浆，测定收缩蛋白：内皮素-1、心肌肌钙蛋白-1、血管紧张素-II 和肌酸激酶-MB，以及氧化/硝化应激标志物（SOD、CAT、MDA、GSH 和 NO）、炎症标志物（TNF-α和 IL-6、NF-kB）和 caspase-3，表明 VCR 降低了升高的血压并逆转了异常心电图。ISO 诱导的内皮素-1、心肌肌钙蛋白-1、血管紧张素-II 和肌酸激酶-MB 升高，VCR 可逆转这些升高。ISO 还增加了 TNF-α、IL-6、NF-kB 的表达，并增加了心脏中 caspase-3 介导的细胞凋亡。然而，VCR 降低了 ISO 诱导的炎症和细胞凋亡，并提高了心脏中的内源性抗氧化剂（GSH、SOD、CAT）的水平，相对于 ISO 对照组。更重要的是，VCR 可防止 ISO 诱导的心肌纤维组织学退化。本研究的结果表明，VCR 治疗通过改善参与兴奋-收缩的蛋白水平，并抑制氧化-炎症和凋亡途径，显著逆转 ISO 诱导的心脏肥厚表型。
