吲哚-3-甲醇对大鼠颈总动脉球囊损伤后Bcl-1、NF-κB和Bcl-X/L蛋白表达的影响

Effect of indole-3-carbinol on protein expressions of Bcl-1,NF-κB and Bcl-X/L in rat carotid artery after balloon lesions

目的研究吲哚-3-甲醇(I3C)对球囊损伤术后大鼠颈动脉血管平滑肌细胞(VSMC)Bcl-1、NF-κB和Bcl-X/L蛋白表达的影响,探讨I3C诱导VSMC凋亡的机制。方法建立35只SD大白鼠颈动脉损伤动物模型,分为对照组(n=5):不给药;实验组(n=30):给予I3C(I3C给药量为12.5、25mg/d和50mg/d,给药时间为4d和7d,共6个亚组,n=5)。术后14d取材。免疫组化检测Bcl-1、NF-κB和Bcl-X/L蛋白的表达。结果术后14d,各组Bcl-1、NF-κB和Bcl-X/L蛋白表达减少。与对照组比较,Bcl-1和Bcl-X/L蛋白表达的25mg7d组,50mg4d组和50mg7d组差异有显著性(P<0.05);NF-κB蛋白表达12.5mg4d组和对照组无显著性差异(P>0.05),其余均有统计学意义(P<0.05)。给药时间和剂量增加时,Bcl-1、NF-κB和Bcl-X/L蛋白表达与对照组差异非常显著(P<0.01)。结论I3C诱导血管损伤后VSMC凋亡的机制主要是通过PI3K-PKB/Akt细胞信号传导途径,下调关键性核因子NF-κB和凋亡抑制蛋白Bcl-X/L表达。

Objective To investigate the effects of indole-3-carbinol （I3C） on the protein expressions of Bcl-1, NF-κB and Bcl-X/L in rat carotid artery after balloon lesions and study the apoptotic mechanisms of VSMC induced by I3C. Methods Thirty-five SD rat models with carotid lesions were randomly divided into 2 groups ： control group （ without treatment, n = 5 ） and experimental group （ treated with I3C, n = 30）. The experimental group was subdivided into 6 groups according to different I3C doses （ 12.5, 25 and 50 mg/d） and different treatment time （4 and 7 d）. Fourteen days later, the target segments were acquired and the 3 protein expressions were measured with SABC method. Results The expressions of Bcl-1, NF-κB and Bcl-X/L were decreased in different experimental groups. Compared with control group, significant difference in expressions of Bcl-1 and Bcl-X/L was found in the experimental groups （4 d, 50 mg/d I3C; 7 d, 25 and 50 mg/d I3C） （P〈0.05 or P 〈0.01 ）. Compared with the control group, all experimental groups except one （4 d, 12.5 mg/d I3C） showed statistical significance in the NF-κB expressions. The difference in the protein expressions of Bcl-1, NF-κB and Bcl-X/L in all experimental groups was more significant than the control group with the increasing of the treatment time and I3C doses （P 〈0. 01 ）. Conclusion The apoptotic mechanism of VSMC induced by I3C after blood vessel injury is mainly through the pathway of PI3K-PKB/Akt cell signaling transduction to downregnlate NF-κB and Bcl-X/L.