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作 者:吴田田[1] 杨广顺[1] 王瑞官[1] 张维[1] 李虎城[1]
机构地区:[1]解放军第309医院肝胆外科,北京100091
出 处:《中华实验外科杂志》2013年第11期2272-2274,共3页Chinese Journal of Experimental Surgery
摘 要:目的 观察雷帕霉素对大鼠肝内胆管缺血后p70S6激酶(p70S6K)含量的影响.方法 将120只雄性SD大鼠随机分4组:A组为对照组(假手术组)28只,B组为假手术+雷帕霉素组28只;C组为缺血组32只,D组为缺血+雷帕霉素组32只.雷帕霉素按每天2.0 mg/kg胃内注入.各实验组于术后第1、3、7天分别处死6只大鼠,术后14d处死全部大鼠.切取肝脏组织,Western blot检测p70S6K含量.多个独立样本比较采用Kruskal-WallisH检验,两样本间的比较经秩转换处理后行one way ANOVA检验,两独立样本比较采用Mann-Whitney U检验.结果 缺血组p70S6K含量增加,术后7d达峰值(2.03±0.14),为对照组的4.43倍(P<0.001);雷帕霉素处理后,p70S6K含量虽有增加,但是峰值(1.03±0.07)仅为缺血组的50% (P <0.01);术后1、7、14 d,缺血+雷帕霉素组p70S6K含量明显低于缺血组(P <0.005).结论 雷帕霉素抑制胆管缺血后p70S6K表达,这可能是雷帕霉素抑制胆管缺血后代偿性增生的机制之一.Objective To investigate the effect of rapamycin on p70s6 kinase (p70S6K) after deprivation of biliary blood supply. Methods Male SD rats were randomly assigned into 4 groups: sham ( n = 28 ) , sham ± rapamycin ( n = 28 ) , ischemia ( n = 32) and isehemia ± rapamycin ( n = 32). In isehe- mia group, complete deprivation of bile duct arterial supply was performed, and in sham group open-close operation was carried out. Daily intake of rapamycin (2 mg/kg) was given in rapamycin-treated groups with the same volume of saline in non-rapamyein-treated groups. Six rats were sacrificed on postoperative day (POD) 1, 3 and 7, and the rest sacrificed on POD 14. Fresh liver tissues were obtained. Western blotting was used to detect the content of p70S6K. Kruskal-Wallis H test was used for comparion of multiple independent samples and the following pairwise comparisons were performed by rank transformation and one way ANOVA. Difference between two independent samples was determined by Mann-Whitney U test. Re- suits According to Western blotting, p70S6K was up-regulated in ischemia group, with the peak level of (2. 03 ± 0. 14), 4.43 folds to sham group ( P 〈 0. 01 ). After administration of rapamycin, there was an increase of p70S6K content in biliary ischemic rats, but the peak level of ( 1.03 ±0, 07) was only 50% of that in ischemia group (P 〈 0. 01 ). Further more, on POD 1,7 and 14, p70S6K content in ischemia ra pamycin group was lnwer than that in ischemia group ( P 〈 0. 005), Conclusion Rapamycin inhibits pro duction of p70S6K, which provides explanation to negative effect of rapamycin on adaptive bile duct prolif eration in response to ischemia.
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