西罗莫司涂层气管支架在气管狭窄动物模型中的应用

Preliminary application of sirolimus-coated tracheal stent in tracheal models of tracheal stenosis

目的:探讨西罗莫司涂层气管支架抑制气管狭窄动物模型肉芽组织增生的有效性。方法:选用2.5~3.0 kg新西兰大耳白兔36只,分成对照组(n=18只),置入普通镍钛合金裸支架,实验组(n=18只),置入西罗莫司涂层镍钛合金裸支架;每组内根据处死时间分为1个月组、2个月组和3个月组,各6只。采用气管切开联合毛刷破坏粘膜法制作气管狭窄动物模型。镍钛合金裸支架36枚,其中18枚浸涂以PLGA为载体的西罗莫司涂层,并进行体外药物缓释实验。透视下行气管支架置入,分别于支架置入后的1个月、2个月和3个月复查胸部CT了解气管狭窄情况,并处死相应组别的兔子,于支架上下两端取标本行HE染色病理检查比较两组气管粘膜增生情况。结果:制作气管狭窄模型过程中1只死于麻醉过深,2只在模型制作后3 d因严重气管粘膜充血水肿死亡,其余33只气管狭窄模型制作成功,补做3只均成功,狭窄程度50%~85%。所有气管狭窄模型均一次性成功置入气管支架。术后1个月、2个月和3个月复查胸部CT显示对照组支架上下缘均有不同程度的肉芽组织增生,以支架上缘为著,最狭窄处平均狭窄程度分别为(81.6±2.8)%、(66.4±1.6)%和(78.2±2.3)%。实验组肉芽组织增生明显较轻,最狭窄处平均狭窄程度分别为(61.68±2.3)%、(45.23±4.5)%和(50.97±3.8)%。处死实验兔于支架上下缘取标本行病理检查见药物涂层支架组纤维素增生和胶原蛋白沉积程度较轻。结论:西罗莫司涂层可有效抑制镍钛合金支架置入后的肉芽组织增生,降低支架置入后再狭窄程度。

Objective:To investigate the effectiveness of sirolimus coated tracheal stent in inhibiting granulation tissue proliferation in tracheal stenosis animal models.Methods:Thirty-six New Zealand white rabbits(2.5~3.0kg)were selected and divided into control group(n=18)and experimental group(n=18).The bare nickel-titanium alloy stents and sirolimus-coated bare nickel-titanium alloy stents were implanted respectively.According to the time of execution,each group was divided into 1 month group,2 months group and 3 months group,with 6 rabbits in each group.Tracheotomy combined with brush destroying mucosa was used to make animal model of tracheal stenosis.Thirty-six bare nickel-titanium alloy scaffolds,18 of which were dipped with sirolimus coatings supported on PLGA,were conducted in vitro drug release experiments.The tracheal stent was implanted under fluoroscopy.The tracheal stenosis was observed by chest CT in 1 month,2 months and 3 months after stent implantation before execution.The specimens were taken from the upper and lower ends of stent for HE staining and pathological examination to compare the tracheal mucosal hyperplasia of the two groups.Results:During the process of making tracheal stenosis models,one died of too deep anesthesia and two died of severe tracheal mucosal congestion and edema three days after making the model.The other 33 tracheal stenosis models were successfully made,and three more were successful,with the degree of stenosis ranging from 50%to 85%.All tracheal stenosis models were successfully implanted with tracheal stents at one time.Chest CT scans at 1 month,2 months and 3 months after operation showed that there were different degrees of granulation tissue proliferation in the upper and lower edges of the stent in the control group.The average stenosis degree at the upper edge of the stent was(81.6±2.8)%,(66.4±1.6)%and(78.2±2.3)%respectively.In the experimental group,the proliferation of granulation tissue was significantly lighter,and the average degree of stenosis at the most narrow sites were(61.68±2.3)%,(45.23±4.5)%and(50.97±3.8)%respectively.Pathological examination showed that the degree of cellulose proliferation and collagen deposition in the drug-coated stent group was slightly lower than that in the control group.Conclusion:Sirolimus coating can effectively inhibit the proliferation of granulation tissue and reduce the degree of restenosis after stent implantation.