Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Mol Biol Rep. 2022 Nov;49(11):10377-10385. doi: 10.1007/s11033-022-07891-3. Epub 2022 Sep 12.
Simvastatin can potentially mitigate acute inflammatory phase of myocardial ischemia-reperfusion injury. However, these effects negatively influenced by its poor bioavailability, low water solubility and high metabolism. Here, we investigated the effects of SIM-loaded nano-niosomes on a rat model of MI/R injury to find a drug delivery method to tackle the barriers.
Nano-niosomes' characteristics were identified using dynamic light scattering and transmission electron microscopy. Fifty male Wistar rats were divided into five groups: Sham; MI/R; MI/R + nano-niosome; MI/R + SIM; MI/R + SIM-loaded nano-niosomes. Left anterior descending artery was ligated for 45 min, and 3 mg/kg SIM, nano-niosomes, or SIM-loaded nano-niosomes was intramyocardially injected ten min before the onset of reperfusion. ELISA assay was used to assess cardiac injury markers (cTnI, CK-MB) and inflammatory cytokines (TNF-α, IL-6, TGF-β, MPC-1). Expression level of MAPK-NF-κB and histopathological changes were evaluated by western blot and hematoxylin & eosin staining, respectively.
the size of nano-niosome was 137 nm, reached to 163 nm when simvastatin was loaded. To achieve optimized niosomes span 80, a drug/cholesterol ratio of 0.4 and seven min of sonication time was applied. Optimized entrapment efficiency of SIM-loaded nano-niosomes was 98.21%. Inflammatory cytokines and the expression level of MAPK and NF-κB were reduced in rats receiving SIM-loaded nano-niosomes compared to MI/R + SIM and MI/R + SIM-loaded nano-niosomes.
Our results showed that SIM-loaded nano-niosomes could act more efficiently than SIM in alleviating the acute inflammatory response of reperfusion injury via downregulating the activation of MAPK-NF-κB.
辛伐他汀可能减轻心肌缺血再灌注损伤的急性炎症期。然而，其生物利用度差、水溶性低和代谢率高，这些影响使其效果不佳。在此，我们研究了 SIM 载纳米囊泡对 MI/R 损伤大鼠模型的影响，以寻找一种克服这些障碍的药物递送方法。
通过动态光散射和透射电子显微镜鉴定纳米囊泡的特征。将 50 只雄性 Wistar 大鼠分为 5 组：假手术组；MI/R 组；MI/R+纳米囊泡组；MI/R+SIM 组；MI/R+SIM 载纳米囊泡组。结扎左前降支 45 分钟，在再灌注开始前 10 分钟，心肌内注射 3mg/kg SIM、纳米囊泡或 SIM 载纳米囊泡。ELISA 法检测心肌损伤标志物（cTnI、CK-MB）和炎症细胞因子（TNF-α、IL-6、TGF-β、MPC-1）。Western blot 法评价 MAPK-NF-κB 表达水平，苏木精-伊红染色法评价心肌组织病理学变化。
纳米囊泡的粒径为 137nm，载 SIM 后达到 163nm。为了获得优化的纳米囊泡，Span80 为 80，药物/胆固醇的比例为 0.4，超声时间为 7 分钟。SIM 载纳米囊泡的包封率为 98.21%。与 MI/R+SIM 和 MI/R+SIM 载纳米囊泡相比，接受 SIM 载纳米囊泡的大鼠炎症细胞因子和 MAPK-NF-κB 表达水平降低。
我们的结果表明，SIM 载纳米囊泡通过下调 MAPK-NF-κB 的激活，比 SIM 更有效地减轻再灌注损伤的急性炎症反应。
