急性肝功能衰竭大鼠模型中程序性死亡-1及其配体的表达

Expressions of programmed death 1 and programmed death ligand 1 in rat model of acute liver failure

的 探讨程序性死亡-1（PD-1）/程序性死亡配体-1（PD-L1）在急性肝功能衰竭大鼠模型中的表达变化及其在肝脏急性炎性损伤中的作用.方法 SD大鼠分为2组：正常组6只,模型组30只,以D-氨基半乳糖（D-Gal）诱导急性肝功能衰竭大鼠模型.造模后分别在12、24、48、72和120 h取大鼠血及肝脏标本,采用RT-PCR法检测肝组织中PD-1 mRNA、PD-L1 mRNA的表达.计量资料组间比较用t检验,相关性检验用Pearson直线相关分析.结果 造模后12 h,大鼠血ALT、AST明显升高,分别为（217.3±33.7）U/L和（397.2±101.3）U/L,显著高于正常组的（30.5±3.1）U/L和（78.6±4.2）U/L,差异有统计学意义（t=-8.921,-6.121,均P＜0.01）,至48 h达高峰.造模后12 h,模型组大鼠PD-1 mRNA表达（0.385±0.074）高于正常组（0.097±0.009）,差异有统计学意义（t=-7.725,P＜0.01）,48 h达高峰（0.927±0.132）,72 h则明显下降.PD-L1mRNA在正常大鼠肝组织中表达很少,模型组PD-L1 mRNA水平逐渐升高,48 h达高峰（0.593±0.105）（t=-10.076,P＜0.01）.造模后大鼠PD-1、PD-L1表达水平与血清ALT水平呈正相关（r=0.807,0.792,P＜0.01）.结论 PD-1/PD-L1表达在急性肝功能衰竭大鼠肝脏炎性损伤中可能起重要作用.

Objective To study the expressions of programmed death 1 （PD-1） and programmed death ligand 1 （PD-L1） in liver injury of acute liver failure （ALF） in rats and the role of PD-1/ PD-L1 in liver inflammatory injury. Methods SD rats were divided into two groups： 6 in normal group and 30 in ALF model group. The ALF models in rats were induced by D-galactosamine （D-Gal）. The sera and hepatic tissue samples were collected at 12, 24, 48, 72 and 120 hours after D-Gal injection. Expressions of PD-1 mRNA and PD-L1 mRNA in hepatic tissue samples were detected by reverse transcription-polymerase chain reaction （RT-PCR）. Comparison of measurement data between groups was done by t test. Correlation test was performed using Pearson linear correlation analysis. Results The levels of alanine animotransferase （ALT） and aspartate animotransferase （AST） at 12 h of D-Gal injection were （217. 3±33. 7） U/L and （397. 2± 101.3） U/L, respectively,which were both significantly higher than those in normal group [（30. 5 ±3. 1） U/L and （78. 6±4.2） U/L, respectively; t=-8. 921 and -6. 121, respectively; both P〈0.01] and peaked at 48 h.The expression of PD-1 mRNA in model group at 12 h （0. 385±0. 074） was significantly higher than that in normal group （0. 097±0.009） （t= -7. 725, P〈0.01） , and peaked at 48 h （0. 927±0. 132）,then decreased obviously at 72 h. The expression of PD-L1 mRNA in the liver tissue of normal rats was very little, while that in model group was increased gradually over time, then peaked at 48 h （0. 593±0. 105; t =- 10. 076, P〈0. 01）. The expressions of PD-1 and PD-L1 were positively correlated with ALT level （r=0. 807 and 0. 792, respectively; both P〈0. 01）. Conclusion The expressions of PD-1/PD-L1 may play an important role in liver inflammatory injury in rat model of acute liver failure.