Objective To investigate the role and mechanism of chemerin in carotid artery remodeling after angioplasty. Methods Chemerin gene was knockdown by chemerin gene deficient lentivirus in carotid injured rats caused by angioplasty. Chemerin mRNA was tested by real time PCR. After chemerin was knockdown, the intimal morphology of carotid was surveyed and the proliferation of vascular smooth muscle cells ( VSMCs) was explored by BrdU staining. The protein levels of phosphorylated-p38 MAPK, phosphorylated-ERK 1 / 2, phosphorylated-JNK were investigated by Western blot analysis. Results Local chemerin expression of carotid was significantly suppressed by chemerin deficient lentivirus (P < 0. 001). In carotid injured rats, significant intimal hyperplasia and VSMCs proliferation occurred. The protein levels of p-p38 MAPK, p-ERK 1 / 2, p-JNK were up-regulated. After chemerin was knockdown, the intimal hyperplasia of carotid and VSMCs proliferation were significantly attenuated and the protein levels of p-p38 MAPK, p-ERK 1 / 2, p-JNK were simultaneously down-regulated. Conclusions Chemerin may stimulate rat carotid neointimal remodeling by activation of MAPK.%目的：观察抑制趋化素基因对大鼠颈动脉球囊损伤后血管重塑的作用及机制。方法构建大鼠颈动脉球囊损伤模型,模型组只进行球囊损伤术,不进行局部转染；慢病毒对照组球囊损伤术后于颈总动脉局部灌注对照慢病毒30 min；慢病毒抑制组大鼠在球囊损伤术后于颈总动脉局部灌注趋化素基因缺陷慢病毒30 min。在颈动脉局部转染趋化素基因缺陷性慢病毒,转染后第3天采用Real-time PCR 检测颈动脉局部组织中趋化素的表达水平。观察抑制趋化素表达后颈动脉的内膜形态变化。采用5-溴-脱氧脲苷(BrdU)法检测颈动脉组织中血管平滑肌细胞的增殖情况,蛋白质免疫印迹法检测颈动脉组织中磷酸化的 p38丝裂原活化蛋白激酶(p-p38 MAPK)、磷酸化细胞外调节蛋白激酶(p-ERK 1/2)、磷酸化 c-jun 氨基末端激酶(p-JNK)的水平。结果在转染趋化素基因缺陷慢病毒后第3天,慢病毒抑制组趋化素 mRNA 水平显著低于模型组[(0.1633±0.02)比(1.005±0.02), P ＜0.001],差异有统计学意义。球囊损伤导致大鼠颈动脉内膜 BrdU 阳性颗粒明显增加,内膜显著增生,p-p38 MAPK、p-ERK 1/2、p-JNK 的蛋白水平显著上升；抑制颈动脉中趋化素表达后,大鼠颈动脉内膜 BrdU 阳性颗粒减少,内膜增生程度减轻,p-p38 MAPK 、p-ERK 1/2、p-JNK 的蛋白表达水平也随之显著下降。结论趋化素可以通过上调 p38 MAPK、ERK 1/2及 JNK 的磷酸化水平,促进颈动脉损伤后内膜增生的发生。
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