大蒜素局部应用对动脉损伤后新生内膜及NF-κB、TNF-α表达的影响

Effects of Local Application of Allicin on Neointimal Hyperplasia and the Expressions of NF-ΚB and TNF-α after Balloon Injury in Rat Carotid Artery

目的观察大蒜素局部应用在大鼠颈总动脉球囊损伤模型中对新生内膜及NF-κB、TNF-α表达水平的影响。方法 30只SD雄性大鼠随机分为5组:假手术组,左侧颈总动脉不行球囊损伤;对照组,大鼠左侧颈总动脉球囊损伤后立即经带孔球囊导管给予生理盐水;药物组,大鼠左侧颈总动脉球囊损伤后立即经带孔球囊导管给予大蒜素高(100μg/ml)、中(50μg/ml)、低(25μg/ml)浓度,共3组。每组于术后14 d取颈总动脉组织,行HE染色观察新生内膜组织形态学改变,计算内膜面积(IA),及内膜/中膜面积比(IA/MA);免疫组织化学方法检测NF-κB、TNF-α的表达水平。结果假手术组未见内膜增生,对照组与假手术组相比新生内膜明显增厚,药物组较对照组新生IA及IA/MA显著降低(P<0.01),但是药物组各组间差别无统计学意义。假手术组未见NF-κB、TNF-α染色阳性细胞,药物组与对照组相比NF-κB、TNF-α阳性细胞百分比显著降低(P<0.01),并且呈浓度依赖性。结论大蒜素通过局部短时间应用可以抑制血管球囊损伤后新生内膜增生,其机制可能是通过抑制TNF-α/NF-κB信号通路实现的。

Objective To study the effects of local application of allicin on neointimal hyperplasia and the expressions of NF- κB and TNF-α after balloon injury in rat carotid artery. Methods A total of 30 SD rats were divided randomly into 5 groups, Sham group which were operated without balloon injury;three treatment groups were given allicin by 100 μ/ml,50μg/ml and 25 μg/ml,after the left common carotid arteries were injured by balloon,while the control group were given the same amount of saline instead. For each group, rats were killed 14 days after operation and the carotid artery was taken. Neointimal was detected histomorphologically using HE staining,and the expression of NF-κB and TNF-α were detected by immunohistochernistry. The area of intima and ratios of intima to media were measured using HE stain. Results The intimal thickness was increased in control group compared to sham group, in which there was no hyperplasia. The area of intima and ratios of intima to media were significantly decreased in treatment groups compared to control group（P 〈0. 01 ）, but there were no statistic difference between treatment groups. The expression of NF-κB and TNF-α were significantly decreased in treatment groups compared to control group（ P 〈 0. 01 ）, which was dose-dependent. And there was no expression of NF-κB or TNF-α in sham group. Conclusion These studies demonstrated that local application of allicin inhibited neointimal hyperplasia in rat carotid artery after balloon injury. The mechanism may be that it can specifically inhibit the expression of NF-KB and TNF-α, which was the key inflammatory factors. [ Key wdrds ] Allicin ; Balloon injury ; Neointimal ; NF-KB ; TNF-α