**标题**：小檗碱纳米粒对抗三氧化二砷心脏毒性的保护作用。 **摘要**：目的：探讨小檗碱纳米粒（BBR-NP）对三氧化二砷（ATO）诱导的心脏毒性的保护作用及可能机制。方法：将大鼠随机分为对照组、ATO 组、BBR 组和 BBR-NP 组。通过尾静脉注射 ATO 建立大鼠心脏毒性模型，BBR 组和 BBR-NP 组大鼠分别给予 BBR 和 BBR-NP 预处理。检测大鼠血清中肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）的活性，以及心肌组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）的水平。采用 HE 染色观察心肌组织病理学变化，Western blot 检测心肌组织中凋亡相关蛋白 Bcl-2、Bax 和 caspase-3 的表达。结果：与对照组相比，ATO 组大鼠血清中 CK-MB 和 LDH 活性显著升高（P<0.05），心肌组织中 SOD、GSH-Px 活性降低，MDA 水平升高（P<0.05）；心肌组织病理学损伤明显，凋亡相关蛋白 Bcl-2 表达降低，Bax 和 caspase-3 表达升高（P<0.05）。与 ATO 组相比，BBR 组和 BBR-NP 组大鼠血清中 CK-MB 和 LDH 活性降低，心肌组织中 SOD、GSH-Px 活性升高，MDA 水平降低（P<0.05）；心肌组织病理学损伤减轻，凋亡相关蛋白 Bcl-2 表达升高，Bax 和 caspase-3 表达降低（P<0.05）。结论：BBR-NP 对 ATO 诱导的大鼠心脏毒性具有保护作用，其机制可能与抑制氧化应激和细胞凋亡有关。
Protective Effect of Berberine Nanoparticles Against Cardiotoxic Effects of Arsenic Trioxide.
机构信息
Geriatric Health Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.
出版信息
Cardiovasc Toxicol. 2024 Dec;24(12):1311-1316. doi: 10.1007/s12012-024-09927-5. Epub 2024 Sep 30.
Arsenic trioxide (ATO) is a potent and highly effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, the clinical use of ATO is hampered by different cardiopathologic outcomes, such as arrhythmia and heart failure. Berberine has several beneficial effects because of its antioxidant activity; however, the potential cardioprotective function of this alkaloid against arsenic-induced cardiac toxicity has not been fully investigated. In this study, we evaluated the effect of ATO in rat heart tissue and the effect of berberine nanoparticles (NB) on cardiac enzyme levels, oxidative stress (OS) indices, and histopathological changes in heart tissue. Thirty Wistar rats were randomly allocated into five groups (n = 6): (1) Control animals that received 0.5 cc saline via gavage, (2) ATO group (4 mg/kg), (3) ATO + NB (2.5 mg/kg), (4) ATO + NB (5 mg/kg), and (5) ATO + NB (10 mg/kg) groups. Treatments were administered intraperitoneally for 45 days. Cardiac enzymes and OS biomarkers in heart tissue were measured. Histopathological examination of the heart tissue was also conducted at the end of the study. ATO injection significantly increased cardiac enzyme levels and OS biomarkers in rat's heart tissue. It also changed the histological features of the heart. NB administration significantly decreased the serum and tissue levels of cardiac enzyme and OS biomarkers in ATO-exposed animals (p < 0.05) and improved myocardial structural damage. NB, potent antioxidant, can reduce the unfavorable effects of ATO in rat heart tissue by balancing OS markers.
三氧化二砷（ATO）是治疗急性早幼粒细胞白血病的有效化疗药物。然而，由于不同的心脏病理结果，如心律失常和心力衰竭，ATO 的临床应用受到了阻碍。小檗碱由于其抗氧化活性具有多种有益作用；然而，这种生物碱对砷诱导的心脏毒性的潜在心脏保护作用尚未得到充分研究。在这项研究中，我们评估了 ATO 在大鼠心脏组织中的作用以及小檗碱纳米颗粒（NB）对心脏酶水平、氧化应激（OS）指标和心脏组织组织学变化的影响。30 只 Wistar 大鼠随机分为五组（n = 6）：（1）对照组，灌胃给予 0.5 cc 生理盐水；（2）ATO 组（4mg/kg）；（3）ATO+NB（2.5mg/kg）；（4）ATO+NB（5mg/kg）；（5）ATO+NB（10mg/kg）组。治疗采用腹腔注射，共 45 天。测量心脏组织中的心脏酶和 OS 生物标志物。研究结束时还对心脏组织进行了组织学检查。ATO 注射显著增加了大鼠心脏组织中的心脏酶水平和 OS 生物标志物。它还改变了心脏的组织学特征。NB 给药显著降低了暴露于 ATO 的动物的血清和组织中的心脏酶和 OS 生物标志物水平（p<0.05），并改善了心肌结构损伤。NB，一种有效的抗氧化剂，通过平衡 OS 标志物，可以减少 ATO 在大鼠心脏组织中的不利影响。
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