The Experimental Research On Proto-oncogene N33and Interleukin-24Gene Expression In Autologous Vein Graft

Objective: To study proto-oncogene N33and human interleukin-24(IL-24) gene expression dynamics in intimal hyperplasia tissues after autologous vein graft, and investigate their roles in intimal hyperplasia, thus to combat graft intimal hyperplasia and stenosis, occlusion, provide genetic intervention targets.Methods:Wistar rats56, their right external jugular vein stump are coincided with ipsilateral common carotid to establish the autologous vein graft model. The animals were sacrificed after surgery randomly on6h、1d、3d、7d、14d、28d and42d corresponding time points to take the transplanted vein and at the same time take the contralateral normal veins as controls. Take HE staining to observe the histological changes. With computer image analysis system to measure the thickness, area and stenosis rate of hyperplastic endometrium, and detect the proto-oncogene N33and human leukocyte interleukin-24(IL-24) gene corresponding protein expressions through applying immunohistochemical staining method.Results:1. Normal venous intima have no positive expression of proto-oncogene N33protein. After autogenous vein graft3d,7d,14d, intimal hyperplasia became clear, the proto-oncogene N33protein expression was significantly increased trend, the positive cell expression rates at three time points were20.3±3.1%,28.7±2.4%,45.6±5.6%, reached the peak on14day, the three phase and a normal vein group (0.7±0.2%) differences were statistically significant (P<0.05).2. The degree of intimal hyperplasia tend to reduce after4w, the proto-oncogene N33protein expression were also decreasing, the positive cell rate was33.5±4.5%, the degree of intimal hyperplasia in6w further reduce compared with4w,the corresponding protein expression was lower intensity,the positive cell rate was27.5±3.4%,both differences were statistically significant compared with postoperative2w and normal vein group (P<0.05). The positive cell expression rate on postoperative6w was not statistically significant (P>0.05) compared with postoperative4w.3. IL-24protein expression was strong in normal vein, showing a strong positive.The positive percentage of expressing cells to total cells in the unit field of view was25.7±2.3%.The intimal hyperplasia of autologous vein grafting was gradually increasing,while IL-24protein expression showed a gradual weakening trend.Three relatively obvious changes phase(postoperative1w,2w,4w),the positive cells percentage were20.1±3.1%,14.3±1.4%,7.5±1.6%within the unit vision.The positive rate on postoperative2w was significantly reduced compared with normal vein group(P<0.05);The positive rate on postoperative4w was very statistically significant compared with normal vein group (P <0.01).The positive cell expression rate on postoperative6w (5.8±1.4%) was not statistically significant (P>0.05) compared with postoperative4w.Conclusions:1. The activation and expression of proto-oncogene N33can promote the development of intimal hyperplasia after vein grafting.2. IL-24gene normal expression can inhibit the development of intimal hyperplasia after vein grafting.3. The proto-oncogene N33and IL-24gene may be new intervention targets for gene therapy of intimal hyperplasia after vein grafting.