雷公藤内酯醇洗脱支架抑制小型猪冠脉再狭窄研究

The Effect and Mechanism of Triptolide-eluting Stent on Preventing Porcine Coronary Restenosis In Miniwine

目的评价雷公藤内酯醇洗脱支架对预防小型猪冠状动脉模型再狭窄的疗效,研究其量效关系与安全性。方法将30只西藏小型猪分为不锈钢裸金属支架组、雷帕霉素支架组、雷公藤内酯醇60μg支架组、雷公藤内酯醇100μg支架组和雷公藤内酯醇200μg支架组等5组,设立7d组和28d组两个观察终点。每只猪选择左前降支和右冠脉分别置入同一类型支架各1枚。共置入支架60枚。28d组于术后28d行冠状动脉造影,术后处死动物,取出支架血管,行病理组织学分析。7d组于术后7d处死动物,取支架血管行核因子NF-κB免疫组化检测。所有小型猪术前术后行血常规和血肝肾功能检查。结果支架植入后28d组、雷公藤内酯醇100μg支架组和雷帕霉素支架组最小内径相似(P>0.05),均大于不锈钢裸金属支架组(P<0.05)。雷公藤内酯醇100μg支架组与雷帕霉素支架组相比新生内膜厚度相似(P>0.05),均明显小于不锈钢裸金属支架组、雷公藤内酯醇60μg支架组和雷公藤内酯醇200μg支架组(P<0.05)。雷公藤内酯醇100μg支架组与雷帕霉素支架组相比狭窄程度相似(P>0.05),均明显小于不锈钢裸金属支架组、雷公藤内酯醇60μg支架组和雷公藤内酯醇200μg支架组(P<0.05)。支架植入后雷公藤内酯醇100μg支架组NF-κB阳性细胞数比不锈钢裸金属支架组、雷帕霉素支架组、雷公藤内酯醇60μg支架组和雷公藤内酯醇200μg支架组减少(P<0.05),其它4组无统计学意义(P>0.05)。结论雷公藤内酯醇支架能抑制冠脉内膜增生,在支架植入4周内能预防再狭窄,无毒副作用,且其效应呈剂量依赖性。

Objective To evaluate the effect of triptolide eluting- stent on preventing in- stent restenosis in mini porcine models, and to investigate it＇s dose-effect relationship and safety. Methods 30 Tibet mini porcine were randomly divided into five groups： bare metal stent group, rapamycin-eluting stent group, triptolide-eluting stent 60μg group, triptolide-eluting stent 100 μg group and triptolide-eluting stent 200 μg group. And two observe end points respectively 7 days and 28 days were set. Each of the animals was implanted one same-type stent into left anterior descending coronary （LAD） and right coronary artery （RCA） re- spectively. Those animals which observe end point is 28 clays were performed coronary angiography and executed in the 28th day after implantation. And the stent implanted arteries were histopathology and histomorphometry analyzed. Those animals which observe end point is 7 days were also executed in the 7^th day after the implantation. And immunocytochemistry analysis was performed to detect the expression NF-κB （ nuclear factor-κB） protein in the stent implanted arteries. Functional parameters of liver and renal （ALT, AST and CREA） in all animals were checked before the implantation and when the animals were executed. Results In the 28 days groups, the in-stent minimal lumen diameter of the rapamycin eluting- stent group was similar to that of triptolide ehuting-stent 100 μg group （ P 〉 0.05 ）, both of which were larger than that of bare metal stent group （ P 〈 0.05 ）. The neointimal area of the troptolide eluting-stent 100 μg group was similar to that of rapamycin eluting- stent group （ P 〉0.05 ）, both of which were apparently smaller than the orther three groups （P 〈0.05 ）. The lumen stenosis rate of the troptolide eluting-stent 100 μg group was similar to that of rapam- ycin eluting- stent group （ P 〉 0.05 ）, both of which were apparently smaller than the orther three groups （ P 〈 0.05）. Immunocytochemistry analysis results showed that compare with bare metal stent group, rapamycin eluting- stent group , troptolide eluting- stent 60 μg and 200μg group the expression of NF-κB protein was less in the troptolide eluting- stent 100 μg group （ P 〈 0.05 ） ; and compare with each other the expression of NF- κB protein in the first four groups was no statistic significance. Conclusion Troptolide eluting- stent can inhibit the proliferation of intimal, and exhibits a dose dependent effect on preventing in- stent restenosis with- in four weeks after the implantation.