载姜黄素和血红素加氧酶-1 基因的胆固醇共轭聚酰胺胺联合用于急性肺损伤的抗炎治疗。
Combined delivery of curcumin and the heme oxygenase-1 gene using cholesterol-conjugated polyamidoamine for anti-inflammatory therapy in acute lung injury.
机构信息
Department of Bioengineering, College of Engineering, Hanyang University, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
Department of Bioengineering, College of Engineering, Hanyang University, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
出版信息
Phytomedicine. 2019 Mar 15;56:165-174. doi: 10.1016/j.phymed.2018.09.240. Epub 2018 Nov 8.
BACKGROUND
Acute lung injury (ALI) is an inflammatory lung disease with a high mortality rate. In this study, combined delivery of the anti-inflammatory compound curcumin and the heme-oxygenase-1 (HO-1) gene using cholesterol-conjugated polyamidoamine was evaluated in a mouse model as a therapeutic option for ALI.
METHODS
Curcumin was loaded into cholesterol-conjugated polyamidoamine (PamChol) micelles, and curcumin-loaded PamChol (PamChol-Cur) was then complexed with plasmid DNA (pDNA) through charge interactions. The pDNA/PamChol-Cur complex was physically characterized by dynamic light scattering, gel retardation, and heparin competition assay. Gene delivery efficiency was measured by luciferase assay. The HO-1 expression plasmid (pHO-1)/PamChol-Cur complex was administrated into the ALI model via intratracheal injection. The anti-inflammatory effect of the pDNA/PamChol-Cur complex was evaluated by ELISA, immunohistochemistry, and hematoxylin and eosin staining.
RESULTS
The pDNA/PamChol-Cur complex had a size of approximately 120 nm with a positive surface charge. The in vitro plasmid DNA (pDNA) delivery efficiency of the pDNA/PamChol-Cur complex into L2 lung epithelial cells was higher than that of pDNA/PamChol. In addition, the curcumin in the pDNA/PamChol-Cur complex inhibited the nuclear translocation of NF-κB, suggesting an anti-inflammatory effect of curcumin. In the ALI animal model, the pHO-1/PamChol-Cur complex delivered the pHO-1 gene more efficiently than pHO-1/PamChol. In addition, the pHO-1/PamChol-Cur complex showed greater anti-inflammatory effects by reducing anti-inflammatory cytokine levels more than delivery of pHO-1/PamChol or PamChol-Cur only.
CONCLUSION
The pHO-1/PamChol-Cur complex had a higher pHO-1 gene-delivery efficiency and greater anti-inflammatory effects than the pHO-1/PamChol complex or PamChol-Cur. Therefore, the combined delivery of curcumin and pHO-1 using PamChol-Cur may be useful for treatment of ALI.
背景
急性肺损伤（ALI）是一种具有高死亡率的炎症性肺病。在这项研究中，使用胆固醇共轭聚酰胺胺（PamChol）评估了抗炎化合物姜黄素和血红素加氧酶-1（HO-1）基因联合递送至小鼠模型作为治疗 ALI 的一种选择。
方法
将姜黄素载入胆固醇共轭聚酰胺胺（PamChol）胶束中，然后通过电荷相互作用使姜黄素载入的 PamChol（PamChol-Cur）与质粒 DNA（pDNA）复合。通过动态光散射、凝胶阻滞和肝素竞争测定法对 pDNA/PamChol-Cur 复合物进行物理表征。通过荧光素酶测定法测量基因转染效率。通过气管内注射将 HO-1 表达质粒（pHO-1）/PamChol-Cur 复合物递送至 ALI 模型。通过 ELISA、免疫组织化学和苏木精和伊红染色评估 pDNA/PamChol-Cur 复合物的抗炎作用。
结果
pDNA/PamChol-Cur 复合物的大小约为 120nm，具有正表面电荷。pDNA/PamChol-Cur 复合物将质粒 DNA（pDNA）递送至 L2 肺上皮细胞的体外质粒 DNA（pDNA）递送效率高于 pDNA/PamChol。此外，pDNA/PamChol-Cur 复合物中的姜黄素抑制 NF-κB 的核易位，表明姜黄素具有抗炎作用。在 ALI 动物模型中，pHO-1/PamChol-Cur 复合物比 pHO-1/PamChol 更有效地递送 pHO-1 基因。此外，pHO-1/PamChol-Cur 复合物通过降低抗炎细胞因子水平比单独递送 pHO-1/PamChol 或 PamChol-Cur 具有更大的抗炎作用。
结论
pHO-1/PamChol-Cur 复合物比 pHO-1/PamChol 复合物或 PamChol-Cur 具有更高的 pHO-1 基因转染效率和更大的抗炎作用。因此，使用 PamChol-Cur 联合递送姜黄素和 pHO-1 可能对 ALI 的治疗有用。
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