抗肿瘤药物DIM防治兔颈动脉球囊损伤术后再狭窄的实验研究  

Prevention and treatment of restenosis after PTA operation in rabbit artery by 3,3'-diindolylmethane

作　　者：蒋伟[1] 黄晶[1] 邓昌明[1] 刘地川[1] 

机构地区：[1]重庆医科大学第二附属医院心内科,重庆400010

出　　处：《中国病理生理杂志》2008年第10期1927-1931,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30527001)

摘　　要：目的:观察DIM对兔血管成形术后再狭窄内膜增生的影响。方法:随机将兔分为假手术组、模型组及大、小剂量DIM治疗组,DIM做成乳剂后予腹腔注射给药。术前3d开始给药,每只给药体积均为2mL/d,假手术组与模型组予等体积的生理盐水。术后4周全部将兔处死,行HE染色观察动脉形态学改变,同时进行PDGF、TGF-β1的免疫组化及bcl-2的原位杂交检测并计算其阳性率。结果:损伤动脉内膜厚度及面积、内膜/中膜面积与内膜/中膜厚度比显著增加。与模型组相比,DIM小剂量组的内膜厚度、内膜面积及内膜/中膜面积与厚度比、PDGF、TGF-β1与bcl-2的阳性表达率均有所下降,但无显著差异(P>0.05),而DIM大剂量组效果显著,具有显著差异(P<0.01)。结论:DIM可以抑制PTCA术后再狭窄的形成,其作用机制可能与抑制血管平滑肌细胞增殖及细胞生长因子和促进细胞凋亡有关。AIM： To evaluate the safety and efficacy of 3,3＇- diindolylmethane （DIM） on neointimal proliferation of rabbit artery after balloon angioplasty. METHODS ： Restenosis models of carotid artery after balloon injury was established in rabbits. 30 rabbits were randomly divided into 4 groups： sham -operated group, model group, low -dose DIM group and high - dose DIM group. DIM was given to the rabbits in low - dose treatment group （2 mg·kg^-1·d^-1 ） and high - dose treatment group （ 8 mg·kg^ - 1 · d^ -1 ） once a day from 3 d before operation to 4 weeks after operation. The two treatment groups were administered with intraperitoneal injection of emulsified DIM, while the other two groups with saline at the same volume. All rabbits were killed after 28 d and carotid arteries were removed. With HE staining, automatic image analysis and immunohistochemistry, artery morphology was observed and the thickness of arterial intima and media was measured. Platelet derived growth factor （PDGF） and transfer growth factor β1（ TGF - β1 ） were examined. The expression of bcl - 2 gene was detected by in situ hybridization （ISH） with computer - assisted picture analysis system. RESULTS ： No significant difference was found between low -dose DIM group and model group in intimal thickness, media thickness, luminal area and the expression of PDGF and TGF- β1 in low- dose DIM group （P 〉0.05 ）. The intimal thickness was decreased in high -dose DIM group compared with model group and low- dose DIM group （P 〈0. 01 ）. The luminal area was significantly larger in high -dose DIM groupthan that in model group and low -dose DIM group （P 〈 0. 01 ）. The expression of PDGF and TGF - β1 in low - dose DIM group was significantly reduced compared with model group and low - dose DIM group （P 〈0. 01 ）. CONCLUSION： The inhibition and treatment of DIM on arterial restenosis are safe and effective. The effect might be achieved by preventing neointimal proliferation and the expression of PDGF

关 键 词：二吲哚甲烷 再狭窄 血管平滑肌细胞 细胞因子类 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学] R36[医药卫生—基础医学]