CAJ | 학술논문

目的探讨雷帕霉素对大鼠肝内胆管缺血术后肝功能、营养状态及生存率的影响.方法 120只雄性SD大鼠随机分为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.术前、术后7d及术后14 d分别测量实验大鼠体质量.各实验组于术后第1、3、7天分别处死6只大鼠,术后14天处死全部大鼠.处死前下腔静脉抽血2～3ml,分别检测血清总胆红素(TBIL)、碱性磷酸酶(ALP)、γ－谷氨酰胺转移酶(GGT)及谷丙转氨酶(ALT).多个独立样本比较采用Kruskal-Wallis H检验,两独立样本间的比较经秩转换后行One Way Anova检验.Kaplan-Meier方法分析各实验组动物生存率.结果缺血组与缺血+雷帕霉素组术后血清TBIL升高,其中缺血+雷帕霉素组术后TBIL水平升高更为显著,术后14 d达(46.99±2.68) mmol/L明显高于缺血组(P＜0.01).术后1～7d,缺血组ALP明显升高,随后趋于平稳；缺血+雷帕霉素组术后血清ALP水平持续上升,术后14 d达(588.74±14.95) U/L,明显高于缺血组(P＜0.05)；术后14 d缺血+雷帕霉素组血清GGT为(10.78 ±0.97)U/L,明显高于缺血组(P＜0.01).缺血组术后体质量下降明显,给予雷帕霉素后,术后7、14d体质量下降幅度增加(P＜0.01).Kaplan-Meier生存分析结果显示:缺血组术后14d累积生存率为68.3％,与照组差异无统计学意义,缺血+雷帕霉素组累积生存率下降明显(55.5％,P＜0.05).结论雷帕霉素加重胆管缺血后肝内胆汁淤积及胆管损伤,影响肝功能恢复,并对大鼠术后营养状态及生存率造成影响.
목적 탐토뢰파매소대대서간내담관결혈술후간공능、영양상태급생존솔적영향.방법 120지웅성SD대서수궤분위4조,A조위대조조(가수술조)28지；B조위가수술+뢰파매소조28지；C조위결혈조32지,D조위결혈+뢰파매소조32지.뢰파매소안매천2.0 mg/kg위내주입.술전、술후7d급술후14 d분별측량실험대서체질량.각실험조우술후제1、3、7천분별처사6지대서,술후14천처사전부대서.처사전하강정맥추혈2～3ml,분별검측혈청총담홍소(TBIL)、감성린산매(ALP)、γ－곡안선알전이매(GGT)급곡병전안매(ALT).다개독립양본비교채용Kruskal-Wallis H검험,량독립양본간적비교경질전환후행One Way Anova검험.Kaplan-Meier방법분석각실험조동물생존솔.결과 결혈조여결혈+뢰파매소조술후혈청TBIL승고,기중결혈+뢰파매소조술후TBIL수평승고경위현저,술후14 d체(46.99±2.68) mmol/L명현고우결혈조(P＜0.01).술후1～7d,결혈조ALP명현승고,수후추우평은；결혈+뢰파매소조술후혈청ALP수평지속상승,술후14 d체(588.74±14.95) U/L,명현고우결혈조(P＜0.05)；술후14 d결혈+뢰파매소조혈청GGT위(10.78 ±0.97)U/L,명현고우결혈조(P＜0.01).결혈조술후체질량하강명현,급여뢰파매소후,술후7、14d체질량하강폭도증가(P＜0.01).Kaplan-Meier생존분석결과현시:결혈조술후14d루적생존솔위68.3％,여조조차이무통계학의의,결혈+뢰파매소조루적생존솔하강명현(55.5％,P＜0.05).결론 뢰파매소가중담관결혈후간내담즙어적급담관손상,영향간공능회복,병대대서술후영양상태급생존솔조성영향.
Objective To investigate the effect of rapamycin on liver function,body weight and survival of experimental rats 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 ischemia + rapamycin (n =32).In ischemia groups,complete deprivation of bile duct arterial supply was performed while in sham groups,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-rapamycin treated groups.Body weight was measured before operation,on postoperative day (POD)7 and POD14.6 rats were sacrificed on POD1,3 and 7 with the rest sacrificed on POD 14.Blood sample (2-3 ml) were obtained,followed by liver function examination including total bilirubin (TBIL),alkaline phosphatase (ALP),GGT and alanine aminotransferase (ALT).Kruskal-Wallis H test was used for comparison of multiple independent samples and the following pair-wise comparisons were performed by rank transformation and ONE WAY ANOVA.Statistic difference was considered when P ＜ 0.05.Survival was analyzed according to Kaplan-Meier method.Results Serum TBIL in ischemia group ascended sharply postoperatively.When rapamycin administrated,TBIL of bile duct ischemic rats reached higher levels on POD 7:(31.11 ±0.82)mmol/L,P＜0.01 and POD 14:(46.99±2.68) mmol/L,P ＜ 0.01.Serum ALP of ischemia group increased from POD 1 to POD 7 and on POD14,increasing tendency ceased.In ischemia + rapamycin group,serum ALP ascended continuously,without remission even on POD14,when ALP was significantly higher than ischemia group (588.74 ± 14.95 ) U/L,P ＜0.05.Based on examination of body weight,in ischemia group,experimental rats experienced weight loss after operation.While in ischemia + rapamycin group,animals suffered more weight loss than ischemia group ( P ＜ 0.01 ).Kaplan-Meier survival analysis showed compared with sham,there was no statistical decrease of cumulative survival in ischemia group,while decrease in ischemia + rapamycin group was significant (55.5％,P ＜ 0.05 ).Conclusion After ischemia injury,liver experienced bile duct injury and cholestasis.Rapamycin exaggerated intra-hepatic cholestasis and bile duct injury,deteriorated liver function and affected negatively on postoperative nutrition and survival.