紫杉醇对移植静脉鳞酸化细胞外信号调节激酶表达的影响

The effect of paclitaxel on the expression of phosphorylated extracellular signal-regulated kinase in vein grafts

目的探讨局部应用紫杉醇对移植静脉壁磷酸化细胞外信号调节激酶（p-ERK-1／2）表达的影响。方法建立家兔颈总动脉自体颈外静脉旁路移植模型，随机分为两组：对照组，移植静脉外膜不做处理；治疗组，相应剂量紫杉醇和20％普罗尼克-F-127胶混合后局部应用到移植静脉。术后2周取材，HE、Masson染色后应用计算机图像分析系统检测移植静脉内膜厚度（I）、中膜厚度（M）、以及内膜厚度／中膜厚度（I／M），用免疫组织化学检测移植静脉p-ERK-1／2和增殖细胞核抗原（PCNA）的表达情况。结果术后2周，治疗组移植静脉I、M以及I／M均明显低于对照组（P〈0．05）；治疗组移植静脉壁血管平滑肌细胞（VSMC）增殖率、p-ERK-1／2阳性率均明显低于对照组（P〈0．05）。结论移植静脉外膜局部应用紫杉醇能明显抑制p-ERK-1／2的表达，减轻内膜增生；抑制p-ERK-1／2的表达有望成为抑制移植静脉内膜增生的一种有效的方法。

Objective To investigate the effect of paclitaxel on the expression of phosphorylated extracellular signal - regulated kinase （p-ERK） in vein grafts. Methods Rabbit models of jugular veins grafted into the common carotid arteries were established and the animals were randomly divided into treat- ment group and control group. In the treatment group, a certain dose of paclitaxel was applied locally in pluronic-F-127 gel ;The control group did not receive local treatment. Vein grafts were harvested at 2 weeks postoperatively, and HE and Masson staining were performed to calculate the thickness of neointima （ I）, media（M） and the ratio of I/M by computer image analysis. Immunohistochemistry was carried out to de- tect the expression of p-ERK and proliferative cell nuclear antigen （PCNA） in vein grafts of both groups. Results At 2 weeks postoperatively,the thickness of neointima, media and the ratio of I/M in the treat- ment group were all significantly less than those in the control group; Moreover, the proliferative rate of vascular smooth muscle cell（VSMC） and the positive rate of p-ERK-1/2 in VSMC in the wall of vein grafts in the treatment group were also significantly less than those in the control group. Conclusion Paclitaxel used on the adventitia in vein grafts could significantly inhibit the expression of p-ERK and reduce the inti- mal hyperplasia. We conclude that inhibiting the expression of p-ERK may be a beneficial component for the treatment of vein grafts diseases.