Zhang Lingjun, Liu Yanmin
Department of Graduate School, Qinghai University, Xining, Qinghai 810016, China.
Department of Cardiovascular Medicine, Qinghai Provincial People's Hospital, Xining, Qinghai 810007, China.
Cardiol Res Pract. 2025 May 8;2025:2729462. doi: 10.1155/crp/2729462. eCollection 2025.
Micro-oxygen therapy can reduce the effects of doxorubicin (DOX) on left ventricular function, cardiac fibrosis, inflammation, and oxidative stress in SD rats. These results suggest the potential of DOX for clinical use. 8-week-old SPF-grade SD male rats were randomly divided into four groups: control group (Ctrl) ( = 10), doxorubicin group (DOX) ( = 10), doxorubicin + conventional oxygen intervention group (DOX+CO) ( = 10), doxorubicin + micropressed oxygen group (DOX+MO)) ( = 10). Left ventricular function was assessed by echocardiography 3 weeks after the end of treatment, and histopathological analysis was conducted utilizing Masson and hematoxylin-eosin (HE) staining. The mRNA expression levels of TGF-β1 and Collagen I were quantified by quantitative real-time PCR (qRT-PCR). Additionally, inflammatory markers, including the concentrations of IL-1β, IL-6, and TNF-α, as well as the activities of SOD and GSH-Px, were measured using enzyme-linked immunosorbent assay (ELISA). The DOX + MO group significantly improved the symptoms of heart failure caused by DOX. The specific results are as follows: The EF significantly increased to 78.037 ± 1.283 (63.259 ± 8.855 in the DOX, ≤ 0.0001); the IVSs increased from 0.243 ± 0.036 to 0.324 ± 0.038 ( ≤ 0.001); the LVPWs increased from 0.263 ± 0.028 to 0.323 ± 0.036 ( ≤ 0.01); the IVSd and the LVPWd increased from 0.171 ± 0.019 to 0.2 ± 0.015 ( ≤ 0.05) and from 0.181 ± 0.032 to 0.234 ± 0.026 ( ≤ 0.01). Among cardiac function indexes, NT-proBNP in DOX + MO group was significantly different from that in DOX group ( ≤ 0.0001). Compared with DOX group, the degree of myocardial fibrosis in DOX + MO group was decreased, and qRT-PCR showed that MO oxygen effectively reduced the mRNA expression of TGF-β1 and collagen1 induced by DOX. In terms of inflammatory indicators, TNF-α ( ≤ 0.0001), IL-1β ( ≤ 0.0001), and IL-6 ( ≤ 0.0001) in DOX + MO group were significantly lower than those in DOX group. In terms of oxidative stress, serum levels of SOD and GSH-PX were decreased in the DOX group, and MO oxygen therapy effectively prevented the reduction of these indexes. On the other hand, the experimental results also showed that DOX + MO group was significantly better than DOX + CO group in terms of cardiac function, inflammation, and oxidative stress. Microbaric oxygen therapy can reduce the effects of DOX on left ventricular function, cardiac fibrosis, inflammation, and oxidative stress in SD rats. These results provide support for clinical studies to evaluate the potential of DOX in clinical applications.
微氧疗法可减轻阿霉素（DOX）对SD大鼠左心室功能、心脏纤维化、炎症及氧化应激的影响。这些结果提示了DOX临床应用的潜力。将8周龄SPF级SD雄性大鼠随机分为四组：对照组（Ctrl）（n = 10）、阿霉素组（DOX）（n = 10）、阿霉素+常规氧干预组（DOX+CO）（n = 10）、阿霉素+微压氧组（DOX+MO）（n = 10）。治疗结束3周后，通过超声心动图评估左心室功能，并采用Masson染色和苏木精-伊红（HE）染色进行组织病理学分析。通过定量实时PCR（qRT-PCR）定量检测转化生长因子-β1（TGF-β1）和I型胶原的mRNA表达水平。此外，采用酶联免疫吸附测定（ELISA）检测炎症标志物，包括白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的浓度以及超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性。DOX+MO组显著改善了DOX所致的心力衰竭症状。具体结果如下：射血分数（EF）显著升高至78.037±1.283（DOX组为63.259±8.855，P≤0.0001）；室间隔厚度（IVSs）从0.243±0.036增加至0.324±0.038（P≤0.001）；左心室后壁厚度（LVPWs）从0.263±0.028增加至0.323±0.036（P≤0.01）；室间隔舒张末期厚度（IVSd）和左心室后壁舒张末期厚度（LVPWd）分别从0.171±0.019增加至0.2±0.015（P≤0.05）和从0.181±0.032增加至0.234±0.026（P≤0.01）。在心功能指标中，DOX+MO组的N末端脑钠肽前体（NT-proBNP）与DOX组相比有显著差异（P≤0.0001）。与DOX组相比，DOX+MO组心肌纤维化程度降低，qRT-PCR显示微压氧有效降低了DOX诱导的TGF-β1和胶原1的mRNA表达。在炎症指标方面，DOX+MO组的TNF-α（P≤0.0001）、IL-1β（P≤0.0001）和IL-6（P≤0.0001）显著低于DOX组。在氧化应激方面，DOX组血清SOD和GSH-PX水平降低，微压氧疗法有效防止了这些指标的降低。另一方面，实验结果还表明，在心脏功能、炎症和氧化应激方面，DOX+MO组显著优于DOX+CO组。微压氧疗法可减轻DOX对SD大鼠左心室功能、心脏纤维化、炎症及氧化应激的影响。这些结果为评估DOX临床应用潜力的临床研究提供了支持。
