中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2014年
8期
1731-1734,封3
,共5页
脂肪间充质干细胞%肝移植术%排斥反应%程序性死亡因子配体1
脂肪間充質榦細胞%肝移植術%排斥反應%程序性死亡因子配體1
지방간충질간세포%간이식술%배척반응%정서성사망인자배체1
Adipose-derived mesenchymal stem cells%Liver transplantation%Rejection%Programmed death ligand 1
目的 探讨脂肪间充质干细胞(ADMSCs)对大鼠肝移植术后排斥反应的影响及其机制.方法 分离培养SD大鼠ADMSCs,构建RNA干扰慢病毒载体转染ADMSCs阻断程序性死亡因子配体1(PD-L1).以SD为供体、Wistar大鼠为受体建立肝移植模型,随机分为A(空白组)、B(对照组)、C(实验组)3组,分别以生理盐水2 ml/ADMSCs(1×107个)/慢病毒转染后ADMSCs(1×10 7个)处理,比较3组大鼠肝移植术后7d肝功能、白细胞介素(IL)-2和IL-10、肝脏病理改变及干细胞凋亡、肝脏组织B细胞淋巴瘤/白血病-2(bcl-2)和bcl相关X蛋白(bax)表达差异.结果 A组血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、IL-2和IL-10水平分别为(188.9±30.8)U/L、(177.1 ±27.9) U/L、(53.8±14.1)μmol/L、(296.32±56.25) ng/L、(74.92±10.98) ng/L;B组为(114.2±22.7) U/L、(134.8±18.1) U/L、(27.7±5.2)μmol/L、(186.36±17.84) ng/L、(194.56±36.87) ng/L;C组为(160.5 ±28.3) U/L、(155.6±25.6) U/L、(41.2±10.3) μmol/L、(250.95±42.68) ng/L、(125.52 ±26.34) ng/L,3组间差异有统计学意义(P＜0.05).原位缺口末端标记法(TUNEL)检测A、B、C组的凋亡指数分别为35.86 ±5.92、12.39±2.23和28.47 ±4.32,3组间差异有统计学意义(P＜0.05).B组大鼠肝移植模型术后bcl-2表达显著高于A组和C组,C组bcl-2表达低于A组;A组bax表达高于A组和C组,C组bax表达高于A组.结论 ADMSCs可显著降低肝移植术后排斥反应,PD-L1通路可能在其抑制排除反应中起重要作用.
目的 探討脂肪間充質榦細胞(ADMSCs)對大鼠肝移植術後排斥反應的影響及其機製.方法 分離培養SD大鼠ADMSCs,構建RNA榦擾慢病毒載體轉染ADMSCs阻斷程序性死亡因子配體1(PD-L1).以SD為供體、Wistar大鼠為受體建立肝移植模型,隨機分為A(空白組)、B(對照組)、C(實驗組)3組,分彆以生理鹽水2 ml/ADMSCs(1×107箇)/慢病毒轉染後ADMSCs(1×10 7箇)處理,比較3組大鼠肝移植術後7d肝功能、白細胞介素(IL)-2和IL-10、肝髒病理改變及榦細胞凋亡、肝髒組織B細胞淋巴瘤/白血病-2(bcl-2)和bcl相關X蛋白(bax)錶達差異.結果 A組血清穀丙轉氨酶(ALT)、穀草轉氨酶(AST)、總膽紅素(TBIL)、IL-2和IL-10水平分彆為(188.9±30.8)U/L、(177.1 ±27.9) U/L、(53.8±14.1)μmol/L、(296.32±56.25) ng/L、(74.92±10.98) ng/L;B組為(114.2±22.7) U/L、(134.8±18.1) U/L、(27.7±5.2)μmol/L、(186.36±17.84) ng/L、(194.56±36.87) ng/L;C組為(160.5 ±28.3) U/L、(155.6±25.6) U/L、(41.2±10.3) μmol/L、(250.95±42.68) ng/L、(125.52 ±26.34) ng/L,3組間差異有統計學意義(P＜0.05).原位缺口末耑標記法(TUNEL)檢測A、B、C組的凋亡指數分彆為35.86 ±5.92、12.39±2.23和28.47 ±4.32,3組間差異有統計學意義(P＜0.05).B組大鼠肝移植模型術後bcl-2錶達顯著高于A組和C組,C組bcl-2錶達低于A組;A組bax錶達高于A組和C組,C組bax錶達高于A組.結論 ADMSCs可顯著降低肝移植術後排斥反應,PD-L1通路可能在其抑製排除反應中起重要作用.
목적 탐토지방간충질간세포(ADMSCs)대대서간이식술후배척반응적영향급기궤제.방법 분리배양SD대서ADMSCs,구건RNA간우만병독재체전염ADMSCs조단정서성사망인자배체1(PD-L1).이SD위공체、Wistar대서위수체건립간이식모형,수궤분위A(공백조)、B(대조조)、C(실험조)3조,분별이생리염수2 ml/ADMSCs(1×107개)/만병독전염후ADMSCs(1×10 7개)처리,비교3조대서간이식술후7d간공능、백세포개소(IL)-2화IL-10、간장병리개변급간세포조망、간장조직B세포림파류/백혈병-2(bcl-2)화bcl상관X단백(bax)표체차이.결과 A조혈청곡병전안매(ALT)、곡초전안매(AST)、총담홍소(TBIL)、IL-2화IL-10수평분별위(188.9±30.8)U/L、(177.1 ±27.9) U/L、(53.8±14.1)μmol/L、(296.32±56.25) ng/L、(74.92±10.98) ng/L;B조위(114.2±22.7) U/L、(134.8±18.1) U/L、(27.7±5.2)μmol/L、(186.36±17.84) ng/L、(194.56±36.87) ng/L;C조위(160.5 ±28.3) U/L、(155.6±25.6) U/L、(41.2±10.3) μmol/L、(250.95±42.68) ng/L、(125.52 ±26.34) ng/L,3조간차이유통계학의의(P＜0.05).원위결구말단표기법(TUNEL)검측A、B、C조적조망지수분별위35.86 ±5.92、12.39±2.23화28.47 ±4.32,3조간차이유통계학의의(P＜0.05).B조대서간이식모형술후bcl-2표체현저고우A조화C조,C조bcl-2표체저우A조;A조bax표체고우A조화C조,C조bax표체고우A조.결론 ADMSCs가현저강저간이식술후배척반응,PD-L1통로가능재기억제배제반응중기중요작용.
Objective The present study was designed to investigate the role of Adipose-derived mesenchymal stem cells (ADMSCs) in hver transplantation and possible mechanisms.Methods Thirty six rats (A,B and C groups) were infused normal saline,ADMSCs,or programmed death ligand 1 (PD-L1)-knockdown ADMSCs,then received orthotopic liver transplantation.Seven days following transplantation,liver function,cytokines,and apoptosis were examined.Results Liver function results showed that the levels of alanine transaminase (ALT),aspartate aminotransferase (AST),total bilirubin (TBIL),interleukin (IL)-2 and IL-10 for those groups were:(188.9 ±30.8) U/L,(177.1 ±27.9) U/L,(53.8 ± 14.1) μmol/L,(296.32 ± 56.25) ng/L,(74.92 ± 10.98) ng/L; (114.2 ± 22.7) U/L,(134.8 ± 18.1) U/L,(27.7±5.2) μmol/L,(186.36 ±17.84) ng/L,(194.56 ±36.87) ng/L; (160.5 ± 28.3) U/L,(155.6±25.6) U/L,(41.2±10.3) μmol/L,(250.95±42.68) ng/L,(125.52 ± 26.34) ng/L.ADMSCs infusion significantly suppressed liver cell apoptosis,increased bcl-2 level,and decreased bax level.These apoptosis-related changes were reduced by PD-L1 knockdown.Conclusion Together these,our results demonstrated the protective role of ADMSCs in liver transplantation rejection,and suggest that PD-L1 underlie the mechanism.
