依达拉奉防治大鼠颈动脉球囊成形术后血管再狭窄

Experimental study on edaravone in prevention of restenosis in rat common carotid balloon angioplasty

目的观察依达拉奉对大鼠颈动脉损伤后再狭窄的防治作用，并探讨其作用机制。方法雄性SD大鼠用数字表法随机分为两组：对照组和治疗组各20只。用2F球囊对大鼠右侧颈总动脉内膜损伤法制作再狭窄模型。治疗组制模后给予依达拉奉3mg／kg，静脉注射，每日2次。对照组损伤后给予等体积的生理盐水。损伤后1、3、7、14和28d原位灌注固定取材，分析病理形态学改变及采用免疫组织化学方法观察基质金属蛋白酶-2（MMP-2）的表达。结果对照组损伤侧动脉14和28d内膜面积分别为（0．240±0、043）mm^2和（0．420±0．063）mm^2，内膜增生指数为0．52±0、06和0．67±0．07，狭窄率为30％±9％和54％±9％，治疗组内膜面积分别为（0、063±0．025）mm^2和（0、116±0．023）mm^2，内膜增生指数为0．24±0、07和0．38±0、05，狭窄率为8％±3％和16％±4％．与对照组同一时间点比较，治疗组内膜面积减少（F分别为50．488和81．119），内膜增生指数（F分别为41．743和48、122）和狭窄率减轻（F分别为24．221和76．453，均P〈0．05）；MMP-2的表达术后3、7、14d增加，阳性细胞率（％）对照组分别为27．16±7．15、22．59±6、68、18．85±4．91，治疗组为15、57±3．62、12．91±1．88、11．96±3．12，治疗组3、7d MMP-2表达较对照组下降，差异有统计学意义（F=8．359，P=0．028和F=7、781，P=0．032）。结论依达拉奉可抑制大鼠颈动脉损伤后再狭窄，这种作用与其抑制MMP-2的表达有关。

Objective To investigate edaravone in prevention of restenosis in rat common eatery arteries balloon angioplasty and the possible mechanism of this process. Methods Forty male SD rats were randomly divided into 2 groups： treatment group （whose intima was injured by balloon and was given edaravone 3 mg/kg by peritoneal injection, bid） and control group （whose intima was injured by ballon and was given the same volume NS as edaravone）. 1, 3, 7, 14 and 28 days after angioplasty, rats were killed and the local arteries were sectioned for analysis of pathological morphology and the expression of matrix metalloproteinase-2 （MMP-2） analyzed by immunohistochemistry. Results Small amounts of smooth muscle cell appeared at the intima of blood vessel 3 days after the artery injured by balloon. Consecutive intima was formed 7 days after artery injury. The intima was even or uneven thickened and the lumen of artery was significant stenosed 14 and 28 days afterwards. In the control group, the intimal area reached （0. 240 ±0. 043 ） mm^2, the intima hyperplasy index were 0. 52 ± 0.06, stenosis ratio were 30% ± 9% 14 days afterwards. The intimal area were （ 0. 420±0. 063 ） mm^2, the intima hyperplasy index were 0. 67±0. 07, stenosis ratio were 54%±9% on day 28. In the treatment group, the intimal area were （0. 063±0. 025 ） mm^2, the intima hyperplasy index were 0. 24±0. 07, stenosis ratio were 8% ± 3% after 14 days. The intimal area were （0. 116± 0. 023 ） mm^2 , the intima hyperplasy index were 0. 38±0.05, stenosis ratio were 16%±4% after 28 days. Compared with control group at the same time, the intimal area （F values were 50. 488 and 81.119 respectively, P 〈 0. 05 ）, the intima hyperplasy index （F values were 41. 743 and 48. 122 respectively, P〈0. 05） and stenosis ratio （F values were 24. 221 and 81. 119 respectively, P 〈 0.05 ） were decreased in treatment group. The expressions of MMP-2 raised after balloon injury. In control group, the expressions of MMP-2 were 27. 16% ± 7. 15% after 3 days, 22. 59% ± 6. 68% after 7 days, 18.85% ±4.91% after 14 days. In the treatment group, it decreased to 15.57% ± 3.62% after 3 days, 12.91%±1.88% after 7 days. Compared with control group, the expressions of MMP-2 in treatment group were lower after 3 days and 7 days （ F = 8. 359, P = 0. 028 and F = 7. 781, P = 0. 032）. Conclusions Edaravone can prevent restenosis in rat common catery after balloon angioplasty. The possible mechanism is that edaravone can inhibit the expressions of MMP-2 in this process.