中华器官移植杂志
中華器官移植雜誌
중화기관이식잡지
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
2012年
4期
232-235
,共4页
王以巧%沈柏用%鲍国清%汪小辉%钱道海%詹茜%潘春鹏%邓侠兴%祝哲诚%彭承宏%李宏为
王以巧%瀋柏用%鮑國清%汪小輝%錢道海%詹茜%潘春鵬%鄧俠興%祝哲誠%彭承宏%李宏為
왕이교%침백용%포국청%왕소휘%전도해%첨천%반춘붕%산협흥%축철성%팽승굉%리굉위
大鼠%肝移植%多粘菌素B
大鼠%肝移植%多粘菌素B
대서%간이식%다점균소B
Rats%Liver transplantation%Polymyxin B
目的 探讨多黏菌素B(PMB)抗内毒素处理对大鼠移植肝的保护作用及相关机制.方法 取SD大鼠,采用双套管法建立原位肝移植模型.采用随机数字表法将受鼠分为对照组(移植前肌注生理盐水0.5 ml)和实验组(移植前肌注含1 mg/ml PMB的生理盐水0.5 ml).肝移植术后,监测受鼠肝肾功能,采用动态浊度法检测门静脉血内毒素水平,采用酶联免疫吸附试验检测血清α肿瘤坏死因子(TNF-α)和白细胞介素6(IL-6)水平,采用聚合酶链反应和蛋白质印迹法检测移植肝组织CD14、Toll样受体4(TLR4)、核因子(NF)-κB、转录因子激活蛋白1(AP-1)等内毒素通路相关指标及热休克蛋白(Hsp)60的蛋白和mRNA水平,观察移植肝组织的病理学改变.结果 再灌注后1h,实验组受鼠门静脉血内毒素水平较对照组明显下降；再灌注后6h,两组均接近正常水平(P＞0.05).术后实验组丙氨酸转氨酶、TNF-α和IL-6的水平较对照组明显下降(P＜0.05),肝组织CD14和TLR4 mRNA的表达明显减少(P＜0.05),肝组织Hsp60 mRNA和蛋白及NF-κB、AP-1蛋白的表达降低(P＜0.05),肝组织病理损伤明显减轻.结论 PMB可降低大鼠肝移植术后门静脉血内毒素水平,改善受者肝功能,减轻血清炎症反应,降低肝组织内毒素通路指标,减轻病理损伤.
目的 探討多黏菌素B(PMB)抗內毒素處理對大鼠移植肝的保護作用及相關機製.方法 取SD大鼠,採用雙套管法建立原位肝移植模型.採用隨機數字錶法將受鼠分為對照組(移植前肌註生理鹽水0.5 ml)和實驗組(移植前肌註含1 mg/ml PMB的生理鹽水0.5 ml).肝移植術後,鑑測受鼠肝腎功能,採用動態濁度法檢測門靜脈血內毒素水平,採用酶聯免疫吸附試驗檢測血清α腫瘤壞死因子(TNF-α)和白細胞介素6(IL-6)水平,採用聚閤酶鏈反應和蛋白質印跡法檢測移植肝組織CD14、Toll樣受體4(TLR4)、覈因子(NF)-κB、轉錄因子激活蛋白1(AP-1)等內毒素通路相關指標及熱休剋蛋白(Hsp)60的蛋白和mRNA水平,觀察移植肝組織的病理學改變.結果 再灌註後1h,實驗組受鼠門靜脈血內毒素水平較對照組明顯下降；再灌註後6h,兩組均接近正常水平(P＞0.05).術後實驗組丙氨痠轉氨酶、TNF-α和IL-6的水平較對照組明顯下降(P＜0.05),肝組織CD14和TLR4 mRNA的錶達明顯減少(P＜0.05),肝組織Hsp60 mRNA和蛋白及NF-κB、AP-1蛋白的錶達降低(P＜0.05),肝組織病理損傷明顯減輕.結論 PMB可降低大鼠肝移植術後門靜脈血內毒素水平,改善受者肝功能,減輕血清炎癥反應,降低肝組織內毒素通路指標,減輕病理損傷.
목적 탐토다점균소B(PMB)항내독소처리대대서이식간적보호작용급상관궤제.방법 취SD대서,채용쌍투관법건립원위간이식모형.채용수궤수자표법장수서분위대조조(이식전기주생리염수0.5 ml)화실험조(이식전기주함1 mg/ml PMB적생리염수0.5 ml).간이식술후,감측수서간신공능,채용동태탁도법검측문정맥혈내독소수평,채용매련면역흡부시험검측혈청α종류배사인자(TNF-α)화백세포개소6(IL-6)수평,채용취합매련반응화단백질인적법검측이식간조직CD14、Toll양수체4(TLR4)、핵인자(NF)-κB、전록인자격활단백1(AP-1)등내독소통로상관지표급열휴극단백(Hsp)60적단백화mRNA수평,관찰이식간조직적병이학개변.결과 재관주후1h,실험조수서문정맥혈내독소수평교대조조명현하강；재관주후6h,량조균접근정상수평(P＞0.05).술후실험조병안산전안매、TNF-α화IL-6적수평교대조조명현하강(P＜0.05),간조직CD14화TLR4 mRNA적표체명현감소(P＜0.05),간조직Hsp60 mRNA화단백급NF-κB、AP-1단백적표체강저(P＜0.05),간조직병리손상명현감경.결론 PMB가강저대서간이식술후문정맥혈내독소수평,개선수자간공능,감경혈청염증반응,강저간조직내독소통로지표,감경병리손상.
Objective To investigate the protective effect of polymyxin B (PMB) to the liver graft after liver transplantation and the underlying mechanism in rats.Methods Male SD rats were selected as the donors and recipients.Non-artery whole liver transplantation model was established in rats according to Kamada's two-cuff method.The rats were divided into two groups by the way of random number table method:control group (normal saline,0.5 ml) and PMB group (PMB,1 mg/ml,0.4 mg/kg+ normal saline 0.5 ml).The levels of portal vein plasma endtotoxin (EU/ml)were determined by endotoxin-analyzing machine of BET-24A. ALT,BUN,and TNF-α,IL-6 in serum were measured by using machine of Automatic Analyzer and ELISA,respectively.The CD14,TLR4,NFκB and AP-1 in the grafts were measured by RT-PCR and Western blotting,and pathological changes were observed. Results PMB decreased the levels of portal vein plasma endotoxin 1 h after reperfusion in PMB group as compared with control group (P＜0.05),and the levels of portal vein plasma endotoxin returned to the normal levels 6 h after reperfusion in both two groups (P＞0.05).After operation,the levels of ALT,TNFα and IL-6 in serum were significantly reduced (P＜0.05),the expression of CD14 and TLR4 mRNA in the grafts was significantly decreased (P＜0.05),the expression of Hsp60 protein and mRNA,and NF-κB and AP1 proteins in the grafts were reduced (P＜0.05),and the pathological damage to the grafts was significantly alleviated in PMB group as compared with control group.Conclusion PMB reduced the levels of portal vein plasma endotoxin after reperfusion in liver transplantation in rats.PMB improved liver function,reduced the injury of inflammatory response,decreased the levels of endotoxin signal pathway markers and alleviated the pathological damage to the grafts.
