一种使用载有他克莫司的可生物降解纳米纤维预防吻合口狭窄的新策略。
A new strategy for prevention of anastomotic stricture using tacrolimus-eluting biodegradable nanofiber.
作者信息
Mutsuga Masato, Narita Yuji, Yamawaki Aika, Satake Makoto, Kaneko Hiroaki, Suematsu Yoshihiro, Usui Akihiko, Ueda Yuichi
机构信息
Department of Cardiothoracic Surgery, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan.
出版信息
J Thorac Cardiovasc Surg. 2009 Mar;137(3):703-9. doi: 10.1016/j.jtcvs.2008.11.017.
OBJECTIVE
We developed a novel sustained drug-eluting device using tacrolimus-eluting biodegradable nanofiber to prevent anastomotic stricture and evaluated the effects in a rat abdominal aortic anastomosis model.
METHODS
In vitro and in vivo tacrolimus release tests for tacrolimus-eluting biodegradable nanofiber were performed to confirm its sustained release. To verify the prevention of anastomotic stricture, tacrolimus-eluting biodegradable nanofiber was placed around the end-to-end anastomosis of abdominal aorta in rats. Five rats were allocated to the following 5 groups: (1) control without tacrolimus-eluting biodegradable nanofiber, (2) 5 mg of nanofiber only (0 wt% of tacrolimus), (3) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.04 wt% of tacrolimus, (4) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.1 wt% of tacrolimus, and (5) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 1.0 wt% of tacrolimus. Morphometric and histologic analyses including immunohistochemistry were performed in each of the groups 2 weeks after the operation.
RESULTS
The tacrolimus-eluting biodegradable nanofiber gradually released tacrolimus for at least 1 month in vitro and in vivo. The ratio of intimal area was significantly reduced in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group compared with the other groups (0.26, 0.24, 0.25, 0.21, and 0.08 in control, 0 wt%, 0.04 wt%, 0.1 wt%, and 1.0 wt%, respectively, P < .05). The cells, which constitute intimal hyperplasia, were positive for smooth muscle actin and SMemb, and factor VIII revealed that endothelial cells covered the surface of the aortic lumen even in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group in immunohistochemistry.
CONCLUSION
Tacrolimus-eluting biodegradable nanofiber reduced neointimal hyperplasia and preserved endothelialization. This device may be useful in the prevention of anastomotic stricture.
目的
我们研发了一种新型的使用载有他克莫司的可生物降解纳米纤维的持续药物洗脱装置，以预防吻合口狭窄，并在大鼠腹主动脉吻合模型中评估其效果。
方法
对载有他克莫司的可生物降解纳米纤维进行体外和体内他克莫司释放试验，以确认其持续释放情况。为验证对吻合口狭窄的预防作用，将载有他克莫司的可生物降解纳米纤维置于大鼠腹主动脉端端吻合处周围。将5只大鼠分为以下5组：（1）无载他克莫司可生物降解纳米纤维的对照组；（2）仅5毫克纳米纤维（他克莫司含量0重量%）；（3）含0.04重量%他克莫司的5毫克载他克莫司可生物降解纳米纤维；（4）含0.1重量%他克莫司的5毫克载他克莫司可生物降解纳米纤维；（5）含1.0重量%他克莫司的5毫克载他克莫司可生物降解纳米纤维。术后2周对每组进行形态计量学和组织学分析，包括免疫组织化学分析。
结果
载有他克莫司的可生物降解纳米纤维在体外和体内至少1个月内逐渐释放他克莫司。与其他组相比，1.0重量%载他克莫司可生物降解纳米纤维组的内膜面积比显著降低（对照组、0重量%、0.04重量%、0.1重量%和1.0重量%组分别为0.26、0.24、0.25、0.21和0.08，P <.05）。构成内膜增生的细胞平滑肌肌动蛋白和SMemb呈阳性，免疫组织化学显示，即使在1.0重量%载他克莫司可生物降解纳米纤维组，因子VIII也显示内皮细胞覆盖主动脉腔表面。
结论
载有他克莫司的可生物降解纳米纤维减少了新生内膜增生并保留了内皮化。该装置可能对预防吻合口狭窄有用。
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