目的 探讨肺组织丝氨酸苏氨酸蛋白激酶-1(Akt1)、Smad3在大鼠肝肺综合征形成中的作用.方法 健康雄性SD大鼠72只,3~4月龄,体重200~ 250 g,采用随机数字表法,将其分为3组(n=24):正常对照组(C组)、假手术组(S组)、胆总管结扎组(CBDL组).S组打开腹腔暴露胆总管后关腹,CBDL组结扎并剪断胆总管后关腹.于术后第1、3和5周(T13)时,随机取8只大鼠,抽取腹主动脉血样后处死取肺脏.腹主动脉血样行血气分析,用RT-PCR法和Western blot法检测肺组织Akt1、Smad3的mRNA及蛋白表达水平;肺组织切片HE染色后观察肺组织微血管的病理学结果.结果 与C组和S组比较,CBDL组T2.3时肺组织Akt1、Smad3的mRNA及其蛋白表达上调,T3时肺泡-动脉血氧分压差增大(P<0.05).CBDL组T3时肺组织微血管明显扩张.结论 大鼠肺组织Akt1、Smad3表达上调参与了肝肺综合征的形成.
Objective To investigate the role of serine threonine protein kinase-1 (Akt1) and Smad3 in lung tissues in development of hepatopulmonary syndrome in rats.Methods Seventy-two healthy male SpragueDawley rats,aged 3-4 months,weighing 200-250 g,were randomly divided into 3 groups (n=24 each):control group (C group),sham operation group (S group) and common bile duct ligation (CBDL) group.The rats were anesthetized with 3% pentobarbital sodium 45 mg/kg.In group CBDL,laparotomy was performed,the common bile duct was ligated and then the abdomen was closed,while the common bile duct was only exposed,but not ligated and then the abdomen was closed in group S.At 1st,3rd and 5th weeks (T1-3),8 rats were chosen randomly in each group and blood samples were obtained from the abdominal aorta for blood gas analysis.The rats were then sacrificed and lungs were isolated to detect the expression of Aktl and Smad3 mRNA and protein in lung tissues (by RT-PCR and Western blot).The lung tissues were sliced and stained with hematoxylin eosin for examination of the pathological changes of pulmonary capillaries.Results Compared with C and S groups,the expression of Akt1 and Smad3 mRNA and protein in lung tissues was significantly up-regulated at T2,3,and alveolar-arterial oxygen tension difference was increased at T3 in CBDL group (P < 0.05).The pulmonary capillary was obviously dilated at T3 in CBDL group.Conclusion The expression of Akt1 and Smad3 in lung tissues is up-regulated,which may be one of the mechanisms of development of hepatopulmonary syndrome in rats.