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NO缓释纳米粒子PEG-b-PAASNO对肺动脉平滑肌细胞的影响
作者:周晓1  姜大伟2  杜强1  张春1  瞿天宇1  李昭玑1  章锐锋1 
单位:1. 东南大学附属中大医院呼吸与危重症医学科, 江苏 南京 210009;
2. 中国科学院大学温州研究所, 浙江 温州 325000
关键词:肺动脉高压 纳米 一氧化氮 聚合物 肺动脉平滑肌细胞 大鼠 
分类号:R543.2
出版年·卷·期(页码):2024·43·第一期(1-8)
摘要:

目的: 探讨一氧化氮(NO)供体聚合物胶束PEG-b-PAASNO(PSNO)对肺动脉平滑肌细胞(PASMC)的影响。方法: 构建PSNO并检测体外释放NO水平。分离并培养大鼠PASMC,CCK8确定PSNO安全浓度范围和有效作用浓度。设立空白对照组、PSNO(250 ng·mL-1)组(PSNO组)、血小板衍生生长因子-BB(PDGF-BB,15 ng·mL-1)组(BB组)和PDGF-BB+PSNO(15 ng·mL-1 PDGF-BB+250 ng·mL-1 PSNO)组(BB+PSNO组),用5-乙炔基-2'脱氧尿嘧啶核苷(EDU)实验、划痕实验和Transwell实验评估PSNO对PASMC增殖、迁移能力的影响,免疫印迹法评估PASMC增殖、收缩、细胞周期相关蛋白[增殖细胞核抗原(PCNA)、钙调蛋白(calponin)、α-平滑肌肌动蛋白(α-SMA)、细胞周期蛋白D1(cyclin D1)、周期蛋白依赖性激酶2(CDK2)]的表达水平。组间比较采用one-way ANOVA分析。结果: 成功构建稳定释放NO的纳米聚合物胶束PSNO,连续释放NO超过48 h,效应呈时间-剂量依赖性。PSNO质量浓度为250 ng·mL-1时有效抑制PDGF-BB诱导的PASMC增殖、迁移;与BB组相比,BB+PSNO组PCNA、calponin、α-SMA、cyclin D1和CDK2蛋白表达水平降低,差异均有统计学意义(P<0.05)。结论: 成功构建一种可以稳定释放NO的纳米聚合物胶束PSNO,其有效释放NO超48h,功能上阻滞PASMC增殖、迁移,并降低PASMC收缩、细胞周期相关蛋白表达水平。

Objective: To study the effect of nitric oxide(NO) donor nano-polymer micelle PEG-b-PAASNO(PSNO) on pulmonary artery smooth muscle cells(PASMC). Methods: PSNO was constructed and its release rate was assayed in vitro. Rat PASMCs were isolated and cultured. The safe concentration range and effective concentration of PSNO were determined by CCK8.The cells were divided into control group,PSNO(250 ng·mL-1)group,platelet-derived growth factor-BB(PDGF-BB,15 ng·mL-1) group(BB group),and PDGF-BB+PSNO(15 ng·mL-1 PDGF-BB,250 ng·mL-1 PSNO) group(BB+PSNO group). 5-ethynyl-2'-deoxyuridine(EDU),Transwell and wound healing were used to examine the effects of PSNO on the proliferation and migration ability of PASMC.The expression levels of proliferation,contraction and cell cycle-related proteins[proliferating cell nuclear antigen(PCNA),calponin,alpha-smooth muscle actin(α-SMA),cyclin D1and cyclin-dependent kinase 2(CDK2)] of PASMC were evaluated by Western blotting. Data were analyzed by one-way ANOVA analysis. Results: A nano-polymer micelle with stable NO release(PSNO) was constructed,and NO was continuously released for more than 48 h in a time-dose-dependent manner. When the concentration of PSNO was 250 ng·mL-1,proliferation and migration of PASMC induced by PDGF-BB were effectively inhibited.Compared with BB group,the expression levels of PCNA,Calponin,α-SMA,cyclin D1 and CDK2 in BB+PSNO group were significantly lower(P<0.05).Conclusion: A nano-polymer micelle with stable release of NO(PSNO) is successfully constructed,which can effectively release NO for more than 48 h,blocking the proliferation and migration of PASMC,and reducing the expression level of PASMC contraction and cell cycle-related proteins.

参考文献:

[1] YUE Y,LI Y,FU S,et al.Osthole inhibits cell proliferation by regulating the TGF-β1/Smad/p38 signaling pathways in pulmonary arterial smooth muscle cells[J].Biomed Pharmacother,2020,121:109640.
[2] ZHU H,KUANG H,LI Q,et al.Effects of oral targeted treatments in pulmonary arterial hypertension:a systematic review and meta-analysis[J].Front Cardiovasc Med,2022,9:915470.
[3] ZHANG R,DAI L Z,XIE W P,et al.Survival of Chinese patients with pulmonary arterial hypertension in the modern treatment era[J].Chest,2011,140(2):301-309.
[4] SIMPSON C E,HASSOUN P M.Promises and pitfalls of multiomics approaches to pulmonary arterial hypertension[J].Am J Respir Crit Care Med,2022,205(12):1377-1379.
[5] 才让卓玛,薛林燕,刘君,等.组织多普勒Tei指数对高海拔地区特发性肺动脉高压患者右心功能的评价[J].现代医学,2018,46(9):983-987.
[6] SEGURA-IBARRA V,WU S,HASSAN N,et al.Nanotherapeutics for treatment of pulmonary arterial hypertension[J].Front Physiol,2018,9:890.
[7] YU B,ICHINOSE F,BLOCH D B,et al.Inhaled nitric oxide[J].Br J Pharmacol,2019,176(2):246-255.
[8] REDAELLI S,MAGLIOCCA A,MALHOTRA R,et al.Nitric oxide:clinical applications in critically ill patients[J].Nitric Oxide,2022,121:20-33.
[9] CHESTER A H,YACOUB M H,MONCADA S.Nitric oxide and pulmonary arterial hypertension[J].Glob Cardiol Sci Pract,2017,2017(2):14.
[10] HAGAN G,PEPKE-ZABA J.Pulmonary hypertension,nitric oxide and nitric oxide-releasing compounds[J].Expert Rev Respir Med,2011,5(2):163-171.
[11] LAM C F,SVIRI S,ILETT K F,et al.Inhaled diazeniumdiolates(NONOates) as selective pulmonary vasodilators[J].Expert Opin Investig Drugs,2002,11(7):897-909.
[12] NAHAR K,RASHID J,ABSAR S,et al.Liposomal aerosols of nitric oxide(NO) donor as a long-acting substitute for the ultra-short-acting inhaled NO in the treatment of PAH[J].Pharm Res,2016,33(7):1696-1710.
[13] 吴郡.基于透明质酸钠的雾化纳米递送体系用于肺部细菌感染治疗的研究[D].北京:北京化工大学,2022.
[14] 章中华,王毅,李永贵,等.壳聚糖在生物医学应用中的研究进展[J].生物医学工程研究,2022,41(3):347-352.
[15] JIANG D,PAN L,YANG X,et al.Photo-controllable burst generation of peroxynitrite based on synergistic interactions of polymeric nitric oxide donors and IR780 for enhancing broad-spectrum antibacterial therapy[J].Acta Biomater,2023,159:259-274.
[16] 王方方,谭建新,肖红.组织块贴壁法行SD大鼠肺内动脉段平滑肌细胞的原代培养及其鉴定[J].海南医学,2011,22(4):22-24.
[17] YANG C,HWANG H H,JEONG S,et al.Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles[J].Int J Nanomedicine,2018,13:6517-6530.
[18] AHMAD A,DEMPSEY S,DANEVA Z,et al.Role of nitric oxide in the cardiovascular and renal systems[J].Int J Mol Sci,2018,19(9):2605.
[19] MOHAMED N A,AHMETAJ-SHALA B,DULUC L,et al.A new NO-releasing nanoformulation for the treatment of pulmonary arterial hypertension[J].J Cardiovasc Transl Res,2016,9(2):162-164.
[20] QUINN J F,WHITTAKER M R,DAVIS T P.Delivering nitric oxide with nanoparticles[J].J Control Release,2015,205:190-205.
[21] CHIARELLI L R,DEGIACOMI G,EGOROVA A,et al.Nitric oxide-releasing compounds for the treatment of lung infections[J].Drug Discov Today,2021,26(2):542-550.
[22] 李汉红,程珍琪,张玉红,等.两亲性嵌段共聚物的自组装及其在生物医学上的应用进展[J].胶体与聚合物,2019,37(3):138-141.
[23] 向慧静,刘劲刚,赵彦利.可释放一氧化氮纳米材料的研究进展[J].物理化学学报,2017,33(5):903-917.
[24] BECK-BROICHSITTER M,MERKEL O M,KISSEL T.Controlled pulmonary drug and gene delivery using polymeric nano-carriers[J].J Control Release,2012,161(2):214-224.
[25] 林必成,韩荣荣,孙硕,等.pH响应的二茂铁基纳米粒抑制下咽癌的研究[J].现代医学,2022,50(5):535-542.
 

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