| 77 | 0 | 44 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探讨纳米微塑料（NPs）暴露致心血管毒性的剂量-效应关系及芒果苷（MGF）的干预效果。方法 将无特定病原体（SPF）级雄性Balb/c小鼠随机分为对照组，0.1、1、10、100mg/kg NPs组和100mg/kg NPs + 120mg/kgMGF组。各组通过连续灌胃给予相应药物28d，1次/d。末次给药后用无创尾套法检测小鼠收缩压（SBP）、舒张压（DBP）和平均动脉血压（MBP）；采用心脏超声测定左室射血分数（LVEF）、左室短轴缩短率（LVFS）和左室收缩末期内径（LVIDs）；苏木精-伊红（HE）和Masson染色观察主动脉和心肌组织病理学变化；采用荧光探针法检测活性氧（ROS）水平，微板法检测血清和心肌组织中丙二醛（MDA）、超氧化物歧化酶（SOD）水平，酶联免疫吸附法（ELISA）检测白细胞介素6（IL-6）、IL-1β和肿瘤坏死因子-α（TNF-α）水平。通过蛋白免疫印迹检测核因子E2相关因子2（Nrf2）、血红素氧合酶1（HO-1）、核因子-κB（NF-κB）和NOD样受体蛋白3（NLRP3）蛋白的表达。结果 与对照组相比，NPs各组呈现剂量依赖性心血管毒性，血压参数SBP、DBP、MBP明显升高（P<0.05）；心功能指标LVEF、LVFS下降且LVIDs增大（P<0.05）；形态学结果显示主动脉内膜部分脱落，中膜弹性纤维断裂且出现血管重构现象，心肌纤维排列紊乱，心脏和主动脉胶原纤维沉积增加（P<0.05）；血清和心肌组织中氧化应激指标ROS和MDA水平升高，SOD活性降低，炎症因子（IL-β、IL-6和TNF-α）水平升高，且呈剂量依赖性（P<0.05）。MGF干预后，上述指标均明显改善，血压和心功能恢复接近1mg/kgNPs组水平，氧化应激标志物和炎症因子水平降低，心脏和主动脉病理损伤减轻（P<0.05）；Nrf2和HO-1表达上升，NF-κB和NLRP3表达下降（P<0.05）。结论 NPs暴露可诱导小鼠产生剂量依赖性的心血管毒性，MGF干预可减轻该损伤，其作用可能与Nrf2/HO-1通路蛋白表达上调及NF-κB/NLRP3通路蛋白表达下调有关。
Abstract：Objective To investigate the dose-response relationship of cardiovascular toxicity induced by nanoplastics (NPs) exposure and the intervention effect of mangiferin (MGF). Methods Specific pathogen-free (SPF) male Balb/c mice were randomly divided into control group， 0.1，1，10，100 mg/kg NPs group， and 100 mg/kg NPs + 120 mg/kg MGF group. Each group was administered via intragastric gavage once daily. After 4 weeks treatments， non-invasive tail-cuff method was employed to measure systolic blood pressure (SBP)， diastolic blood pressure (DBP) and mean arterial blood pressure (MBP). Echocardiography was conducted to assess left ventricular ejection fraction (LVEF)， left ventricular fractional shortening (LVFS)， and left ventricular internal diameter at systole (LVIDs). Hematoxylin-Eosin (H&E) staining and Masson staining were utilized to observe pathological changes in the aorta and myocardial tissue. The level of reactive oxygen species (ROS) was detected using the fluorescent probe. The concentrations of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in serum and myocardial tissue were measured by the microplate assay. The levels of interleukin-6 (IL-6)， interleukin-1β (IL-1β)， and tumor necrosis factor-α (TNF-α) were determined via enzyme-linked immunosorbent assay (ELISA). The expressions of nuclear factor E2-related factor 2 (Nrf2)， heme oxygenase-1 (HO-1)， nuclear factor-κB (NF-κB) and NOD-like receptor protein 3 (NLRP3) were detected by Western blot. Results Compared with the control group， the NPs groups exhibited dose-dependent cardiovascular toxicity: blood pressure parameters (SBP， DBP， MBP) significantly increased (P<0.05). While cardiac function indices (LVEF， LVFS) decreased， and LVIDs increased (P<0.05). Morphological results revealed partial detachment of the aortic intima， fragmentation of elastic fibers in the media， vascular remodeling， disordered arrangement of myocardial fibers， and increased collagen fiber deposition in both heart and aorta (P<0.05). In serum and myocardial tissue， levels of oxidative stress indicators (ROS， MDA) were elevated， SOD activity was reduced， and the levels of inflammatory factors (IL-6， IL-1β， TNF-α) increased， all in a dose-dependent manner (P<0.05). After MGF intervention， the above indicators were significantly improved. Blood pressure and cardiac function recovered to levels close to those in the 1 mg/kg NPs group， the levels of oxidative stress markers and inflammatory factors were decreased， and the pathological damage of the heart and aorta was alleviated (P<0.05). The expressions of Nrf2 and HO-1 were increased， while those of NF-κB and NLRP3 were decreased (P<0.05). Conclusion NPs exposure could induce dose-dependent cardiovascular toxicity in mice， and MGF alleviated NPs-induced cardiovascular injury， accompanied by upregulation of Nrf2/HO-1 and downregulation of NF-κB/NLRP3 protein expression.
[1] Duggal B， Kumar G. Cardiotoxicity of microplastics: an emerging cardiovascular risk factor[J]. Curr Cardiol Rev， 2025， 21(5): e1573403X366030. doi:10.2174/011573403x366030250404105925.
[2] Cheng Y， Chen J， Fu R， et al. Molecular mechanism differences between nanoplastics and microplastics in colon toxicity: nanoplastics induce ferroptosis-mediated immunogenic cell death， while microplastics cause cell metabolic reprogramming[J]. J Nanobiotechnol， 2025， 23(1): 505. doi:10.1186/s12951-025-03545-1.
[3] Shi W， Fuad A R M， Li Y， et al. Biodegradable polymeric nanoparticles increase risk of cardiovascular diseases by inducing endothelium dysfunction and inflammation[J]. J Nanobiotechnol， 2023， 21(1): 65. doi:10.1186/s12951-023-01808-3.
[4] Saha S， Sadhukhan P， Sil P C. Mangiferin: a xanthonoid with multipotent anti-inflammatory potential[J]. Biofactors， 2016， 42(5): 459-74. doi:10.1002/biof.1292.
[5] Suchal K， Malik S， Gamad N， et al. Mangiferin protect myocardial insults through modulation of MAPK/TGF-β pathways[J]. Eur J Pharmacol， 2016， 776: 34-43. doi:10.1016/j.ejphar.2016.02.055.
[6] Yang H， Bai W， Gao L， et al. Mangiferin alleviates hypertension induced by hyperuricemia via increasing nitric oxide releases[J]. J Pharmacol Sci， 2018， 137(2): 154-61. doi:10.1016/j.jphs.2018.05.008.
[7] Cai M， Xia B， Huang W， et al. Micro- and nano-plastics: an emerging contaminant in marine and freshwater ecosystems[J]. J Oceanol Limnol， 2025， 43(2): 343-5. doi:10.1007/s00343-025-5343-2.
[8] Cheng J， Ren C， Cheng R， et al. Mangiferin ameliorates cardiac fibrosis in D-galactose-induced aging rats by inhibiting TGF-β/p38/MK2 signaling pathway[J]. Korean J Physiol Pharmacol， 2021， 25(2): 131-7. doi:10.4196/kjpp.2021.25.2.131.
[9] Haleem N， Kumar P， Zhang C， et al. Microplastics and associated chemicals in drinking water: a review of their occurrence and human health implications[J]. Sci Total Environ， 2024， 912: 169594. doi:10.1016/j.scitotenv.2023.169594.
[10] Marfella R， Prattichizzo F， Sardu C， et al. Microplastics and nanoplastics in atheromas and cardiovascular events[J]. N Engl J Med， 2024， 390(10): 900-10. doi:10.1056/NEJMoa2309822.
[11] Wang X， Jia Z， Zhou X， et al. Nanoplastic-induced vascular endothelial injury and coagulation dysfunction in mice[J]. Sci Total Environ， 2023， 865: 161271. doi:10.1016/j.scitotenv.2022.161271.
[12] Goldsworthy A， O’Callaghan L A， Blum C， et al. Micro-nanoplastic induced cardiovascular disease and dysfunction: a scoping review[J]. J Expo Sci Environ Epidemiol， 2025， 35(5): 746-69. doi:10.1038/s41370-025-00766-2.
[13] 王碧红， 聂潇雨， 丁威杰， 等. 褪黑素通过调控Nrf2通路对甲醛暴露致大鼠急性肺损伤的保护作用[J]. 安徽医科大学学报， 2024， 59(1): 23-8. doi:10.19405/j.cnki.issn1000-1492.2024.01.004.
[14] Fan J， Liu L， Lu Y， et al. Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk[J]. Part Fibre Toxicol， 2024， 21(1): 20. doi:10.1186/s12989-024-00578-6.
[15] Checa J， Aran J M. Reactive oxygen species: drivers of physiological and pathological processes[J]. J Inflamm Res， 2020， 13: 1057-73. doi:10.2147/JIR.S275595.
[16] Fiori E， Davinelli S， Ferrera A， et al. The emerging role of Nrf2 in heart failure: from cardioprotection to therapeutic approaches[J]. ESC Heart Fail， 2025， 12(6): 4000-20. doi:10.1002/ehf2.15406.
[17] Shang Y， University P， Tian J， et al. Mangiferin: sources， anti-inflammatory activities， and molecular mechanisms[J]. J Agric Food Chem， 2025， 73(43): 27145-60. doi:10.1021/acs.jafc.5c06234.
[18] Zheng Y， Xu R， Chen T， et al. Four-pronged reversal of chemotherapy resistance by mangiferin amphiphile[J]. J Control Release， 2025， 378: 776-90. doi:10.1016/j.jconrel.2024.12.057.
基本信息:
中图分类号:X503.1;R965
引用信息:
[1]施汶宁,昌德炜,徐淼,等.芒果苷对纳米微塑料暴露所致小鼠心血管毒性的干预效应[J].安徽医科大学学报().
基金信息:
国家自然科学基金项目（编号：81902937）; 湖北省自然科学基金项目（编号：2025AFD411）
2026-08-25
2026-08-25
2026-08-25