CAJ | 학술논문

目的观察RNA干扰阻断OX40-OX40L共刺激通路对大鼠移植肝存活时间的影响.方法制作DA大鼠到Lewis大鼠的原位肝脏移植模型,移植前取预先制备的5 ml含5×109pfu的pLVTHM-OX40-siRNA重组慢病毒,灌注感染移植供肝30 min,术后观察受者存活时间,移植肝脏进行组织病理学检查;采用ELISA法检测大鼠外周血IL-2,IFN-γ,的水平,并进行受者大鼠脾细胞对供者大鼠脾细胞的混合淋巴细胞反应(MLR).结果转染组受者肝脏移植物的存活时间为(74.00±3.79)d,明显长于对照组和未转染组;转染组移植肝组织炎细胞侵润、间质水肿、肝组织坏死程度较对照组和未转染组减轻,实验组大鼠脾细胞刺激T淋巴细胞增殖的能力降低(P<0.01);移植术后的第7天,转染组血清IL-2浓度为(46.0±8.4)ng/L,IFN-γ浓度为(202.7±14.6)ng/L,均显著低于对照组和未转染组(P<0.05).结论转染靶向OX40的siRNA,在体内可通过阻断OX40-OX40L共刺激通路,抑制大鼠肝脏移植后的排斥反应,延长大鼠移植肝的存活时间.
목적 관찰RNA간우조단OX40-OX40L공자격통로대대서이식간존활시간적영향.방법 제작DA대서도Lewis대서적원위간장이식모형,이식전취예선제비적5 ml함5×109pfu적pLVTHM-OX40-siRNA중조만병독,관주감염이식공간30 min,술후관찰수자존활시간,이식간장진행조직병이학검사;채용ELISA법검측대서외주혈IL-2,IFN-γ,적수평,병진행수자대서비세포대공자대서비세포적혼합림파세포반응(MLR).결과 전염조수자간장이식물적존활시간위(74.00±3.79)d,명현장우대조조화미전염조;전염조이식간조직염세포침윤、간질수종、간조직배사정도교대조조화미전염조감경,실험조대서비세포자격T림파세포증식적능력강저(P<0.01);이식술후적제7천,전염조혈청IL-2농도위(46.0±8.4)ng/L,IFN-γ농도위(202.7±14.6)ng/L,균현저저우대조조화미전염조(P<0.05).결론 전염파향OX40적siRNA,재체내가통과조단OX40-OX40L공자격통로,억제대서간장이식후적배척반응,연장대서이식간적존활시간.
Objective To investigate the effect of blockade of OX40-OX40L co-stimulatory signal on the survival time of rat liver allograft. Methods siRNA-expression vectors were constructed to target OX40. Heterotopic liver transplantation models in rats were established. Liver allografts were infected by in situ peffusion of viral particle (5 x 109 pfu of pLVTHM- OX40siRNA) perioperatively. Histological examination was done. Serum IL-2 and IFN-γ levels were assayed by ELISA, and mix lymphocyte response(MLR) was tested by 3 H-thymidine. Results The survival time of recipients in siRNA treatment group(74.00±3.79) days was significantly longer than that in control group (7.33±0.21 ) days, P <0. 01.The inflammatory cell infiltration and liver tissue structure destruction were very milder in siRNA treatment group than in control group. The concentrations of serum IL-2 and IFN-γ were (46±8.4) ng/L and(202.7±14.6 ) ng/L in siRNA treatment group, which were significantly lower than in control group(286.5±14.6) ng/L and (1682.7±87.9) ng/L respectively (all P<0.05).Conclusion Administration of OX40 siRNA can block OX40-OX40L co-stimulatory signal and inhibit the rejection of liver allograft, so as to prolong the survival time of the grafts after transplantation.