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在大鼠胃出口模型中使用纳米功能化自膨胀金属支架进行局部热处理以抑制胃十二指肠支架诱导的组织增生

Local Heat Treatment for Suppressing Gastroduodenal Stent-Induced Tissue Hyperplasia Using Nanofunctionalized Self-Expandable Metallic Stent in Rat Gastric Outlet Model.

作者信息

Park Jung-Hoon, Kim Min Tae, Kim Kun Yung, Bakheet Nader, Kim Tae-Hyung, Jeon Jae Yong, Park Wooram, Lopera Jorge E, Kim Dong-Hyun, Song Ho-Young

机构信息

Departments of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea.

Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

出版信息

ACS Biomater Sci Eng. 2020 Apr 13;6(4):2450-2458. doi: 10.1021/acsbiomaterials.0c00307. Epub 2020 Mar 19.

Abstract

Despite the promising results from the placement of covered or uncovered self-expandable metallic stent (SEMS) as a nonsurgical therapeutic option for the malignant gastric outlet obstruction (GOO), the long patency of the stent is still limited because of stent-induced tissue hyperplasia. Here, a local heat treatment using a nanofunctionalized SEMS is proposed for suppressing stent-induced tissue hyperplasia during GOO treatment. Highly efficient photothermal gold nanoparticle (GNP) transducer-coated SEMSs (GNP-SEMSs) were prepared for local heat treatment in rat gastric outlet. The in vivo heating temperature in rat gastric outlet model was evaluated and compared with in vitro heating temperature. Three groups of our developed 45 rat gastric outlet models were used: group A, noncoated SEMS only; group B, GNP-SEMS plus local heating; and group C, GNP-SEMS only to investigate in vivo efficacy of GNP-SEMS mediated local heating. Ten rats per group were sacrificed for 4 weeks, and five rats per group were sacrificed immediately after local heat treatment. The in vivo heating temperature was found to be 10.8% lower than the in vitro heating temperatures. GNP-SEMSs were successfully placed through a percutaneous approach into the rat gastric outlet ( = 45). The therapeutic effects of GNP-SEMS were assessed by histologic examination including hematoxylin-eosin, Masson trichrome, immunohistochemistry (TUNEL and CD31), and immunofluorescence (Ki67), and the results showed significant prevention of tissue hyperplasia following stent placement without adjacent gastrointestinal tissue damage. GNP-SEMS-mediated local heating could be an alternative therapeutic option for the suppression of tissue hyperplasia following stent placement in benign and malignant GOOs.

摘要

尽管置入覆膜或非覆膜自膨式金属支架(SEMS)作为恶性胃出口梗阻(GOO)的非手术治疗选择取得了令人鼓舞的结果,但由于支架诱导的组织增生,支架的长期通畅性仍然有限。在此,提出了一种使用纳米功能化SEMS的局部热处理方法,以在GOO治疗期间抑制支架诱导的组织增生。制备了高效光热金纳米颗粒(GNP)换能器涂层的SEMS(GNP-SEMS)用于大鼠胃出口的局部热处理。评估了大鼠胃出口模型中的体内加热温度,并与体外加热温度进行了比较。使用了我们开发的三组共45个大鼠胃出口模型:A组,仅置入未涂层的SEMS;B组,GNP-SEMS加局部加热;C组,仅置入GNP-SEMS,以研究GNP-SEMS介导的局部加热的体内疗效。每组10只大鼠在4周后处死,每组5只大鼠在局部热处理后立即处死。发现体内加热温度比体外加热温度低10.8%。GNP-SEMS通过经皮途径成功置入大鼠胃出口(n = 45)。通过苏木精-伊红染色、Masson三色染色、免疫组织化学(TUNEL和CD31)和免疫荧光(Ki67)等组织学检查评估GNP-SEMS的治疗效果,结果显示在置入支架后可显著预防组织增生,且无相邻胃肠道组织损伤。GNP-SEMS介导的局部加热可能是抑制良性和恶性GOOs置入支架后组织增生的一种替代治疗选择。

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