不同程度胆道外引流对梗阻性黄疸大鼠肝切除术后肝再生的影响
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摘要
目的:探讨不同程度胆道外引流对梗阻性黄疸大鼠肝切除术后肝再生的影响,为肝门部胆管癌术前引流提供理论依据。
方法:建立梗阻性黄疸-再通SD大鼠动物模型(梗阻10天),根据不同引流时间分4组。1、SO-Hx组:即正常大鼠肝切除组;2、ED0-Hx组:胆道外引流0天肝切除组;3、ED2-Hx组:胆道外引流2天肝切除组;4、ED10-Hx组:胆道外引流10天肝切除组。观察术后15天大鼠死亡率、肝功能恢复、术后7天残肝重量/大鼠体重比值,免疫组织化学技术检测术后残肝组织PCNA峰值标记指数、RT-PCR技术检测术后残肝HGF mRNA的表达。
结果:(1)、SO-Hx组术后无动物死亡,ED0-Hx组的死亡率达40%,ED2-Hx组、ED10-Hx组动物术后死亡率明显下降,分别为20%及5%。(2)、ED0-Hx组术后0 h总胆红素水平最高,下降缓慢,至术后168h(7天)时仍高于SO-Hx组约10倍,两组相比差异有统计学意义(p<0.05);门冬氨酸氨基转移酶也明显升高。ED2-Hx组术后0h总胆红素及转氨酶较ED0-Hx组有大幅度下降,但恢复过程却与ED0-Hx组相似,至术后168h (7天)时总胆红素仍高于SO-Hx组约5倍,两组相比差异均有统计学意义(p<0.05);ED10-Hx组行肝切除术后168h (7天)内总胆红素及门冬氨酸氨基转移酶处于较为正常水平,与SO-Hx组相比差异无显著性意义(p>0.05)。(3)、术后7天残肝重量/体重比值显示SO-Hx组残肝增生最为明显,各引流组残肝增生明显减弱,与SO-Hx组相比差异有统计学意义(p<0.05)。ED2-Hx组残肝增生较ED0-Hx组增加,ED10-Hx残肝增生较ED0-Hx组及ED2-Hx组增加,各组相比差异均有统计学意义(p<0.05)。(4)、各引流组术后肝组织PCNA峰值标记指数及HGF mRNA的表达峰值较SO-Hx组弱,与SO-Hx组比较差异有统计学意义(p<0.05)。ED0-Hx组、ED2-Hx组、ED10-Hx组随着引流时间的延长PCNA峰值标记指数及HGF mRNA表达峰值逐渐增加,各组相比差异有统计学意义(p<0.05)。
结论:1、胆道梗阻导致的高胆红素血症明显抑制肝切除术后的肝再生,大鼠死亡率高。胆管再通后随着肝功能改善,这种抑制状态逐渐恢复,行肝切除术后大鼠死亡率降低。2、在胆道外引流后的短时间内,肝功能虽明显改善,但是肝再生仍处于抑制状态,死亡率仍较高,不宜手术。3、较长时间胆道外引流、肝功能得到充分恢复才能较为安全地行扩大肝叶切除术。
Objective: To research the effect of different degrees of biliary drainage on obstructive jaundice rats and liver regeneration after hepatectomy, providing a theoretical basis for the preoperative biliary drainage to hilar cholangiocarcinoma.
Methods: Builting the external biliary drainage animal model(obstruct 10 days), we divided all rats in four groups according to different drainaging times. 1, SO-Hx group: Normal rat hepatectomy group; 2, ED0-Hx group: External biliary drainage 0 days hepatectomy group; 3, ED2-Hx group: External biliary drainage 2 days hepatectomy group; 4, ED10-Hx group: External biliary drainage 10 days hepatectomy group. Observe the mortality of rats 15 days later,the liver functional rehabilitation and the ratio of residual liver weight/rat weight 7 days later. Detect the peak expression of PCNA and HGF mRNA in residual hepatic tissue by immunohistochemistry and RT-PCR technology.
Results: (1), The mortality in ED0-Hx group was very high(up to 40 percent), significantly higher than that in SO-Hx Group (0 percent). The mortality in ED2-Hx and ED10-Hx group decreased significantly, to 20 percent and 5 percent, but still higher than the SO-Hx group. (2), The total bilirubin level in ED0-Hx group was highest at 0h and still about 10 times higher than that in SO-Hx group 168h (7 days)later, the difference between the two groups were statistically significant (p<0.05) ; Aspartate aminotransferase also increased significantly and the recovery process was simillar to total bilirubin. Although the total bilirubin level in ED2-Hx group has dropped substantially at 0h, but the recovery process is similar to ED0-Hx groups. 168 h (7 days) later the total bilirubin still about 5 times higher than the that in SO-Hx group, the difference between the two groups were statistically significant (p <0.05); The total bilirubin and aspartate aminotransferase in ED10-Hx group are in a normal level during the 168h (7 days) after hepatectomy, Compared to the SO-Hx group there was not statistically difference (p>0.05). (3). The ratio of residual liver weight / rat weight 7 days after hepatectomy in SO-Hx was highest. Residual liver proliferation in the drainage groups significantly weakened, comparing to SO-Hx group the differences were statistically significant (p <0.05). Residual liver proliferation in ED2-Hx group was higher than that in ED0-Hx group and in ED10-Hx group it was highe than that in ED0-Hx group and ED2-Hx groups, comparing to eath other the differences were statistically significant(p<0.05). (4), The peak expression of PCNA and HGF mRNA increased after the external biliary drainage. The peak expression of PCNA and HGF mRNA in the external biliary drainage groups were lower than that in SO-Hx group, the differences were statistically significant (p<0.05). The peak expression of PCNA and HGF mRNA in ED2-Hx group was higher than that in ED0-Hx group, The peak expression of PCNA in ED10-Hx group was higher than that in ED2-Hx group, the differences between eath other were statistically significant (p <0.05).
Conclusion: 1. The hyperbilirubinemia caused by Biliary obstruction significantly inhibited the liver regeneration. liver function improved after external biliary drainage and the condition gradually recovered. Rat mortality reduced. 2. Although liver function inproved greatly in a short time after external biliary drainage, the liver regeneration was still in the inhibiting condition, the mortality was still high that was not suitable for the surgery. 3. It should be a long time drainage and after the liver function had been restored completely that the surgery for expanding hepatectomy can be safe.
方法:建立梗阻性黄疸-再通SD大鼠动物模型(梗阻10天),根据不同引流时间分4组。1、SO-Hx组:即正常大鼠肝切除组;2、ED0-Hx组:胆道外引流0天肝切除组;3、ED2-Hx组:胆道外引流2天肝切除组;4、ED10-Hx组:胆道外引流10天肝切除组。观察术后15天大鼠死亡率、肝功能恢复、术后7天残肝重量/大鼠体重比值,免疫组织化学技术检测术后残肝组织PCNA峰值标记指数、RT-PCR技术检测术后残肝HGF mRNA的表达。
结果:(1)、SO-Hx组术后无动物死亡,ED0-Hx组的死亡率达40%,ED2-Hx组、ED10-Hx组动物术后死亡率明显下降,分别为20%及5%。(2)、ED0-Hx组术后0 h总胆红素水平最高,下降缓慢,至术后168h(7天)时仍高于SO-Hx组约10倍,两组相比差异有统计学意义(p<0.05);门冬氨酸氨基转移酶也明显升高。ED2-Hx组术后0h总胆红素及转氨酶较ED0-Hx组有大幅度下降,但恢复过程却与ED0-Hx组相似,至术后168h (7天)时总胆红素仍高于SO-Hx组约5倍,两组相比差异均有统计学意义(p<0.05);ED10-Hx组行肝切除术后168h (7天)内总胆红素及门冬氨酸氨基转移酶处于较为正常水平,与SO-Hx组相比差异无显著性意义(p>0.05)。(3)、术后7天残肝重量/体重比值显示SO-Hx组残肝增生最为明显,各引流组残肝增生明显减弱,与SO-Hx组相比差异有统计学意义(p<0.05)。ED2-Hx组残肝增生较ED0-Hx组增加,ED10-Hx残肝增生较ED0-Hx组及ED2-Hx组增加,各组相比差异均有统计学意义(p<0.05)。(4)、各引流组术后肝组织PCNA峰值标记指数及HGF mRNA的表达峰值较SO-Hx组弱,与SO-Hx组比较差异有统计学意义(p<0.05)。ED0-Hx组、ED2-Hx组、ED10-Hx组随着引流时间的延长PCNA峰值标记指数及HGF mRNA表达峰值逐渐增加,各组相比差异有统计学意义(p<0.05)。
结论:1、胆道梗阻导致的高胆红素血症明显抑制肝切除术后的肝再生,大鼠死亡率高。胆管再通后随着肝功能改善,这种抑制状态逐渐恢复,行肝切除术后大鼠死亡率降低。2、在胆道外引流后的短时间内,肝功能虽明显改善,但是肝再生仍处于抑制状态,死亡率仍较高,不宜手术。3、较长时间胆道外引流、肝功能得到充分恢复才能较为安全地行扩大肝叶切除术。
Objective: To research the effect of different degrees of biliary drainage on obstructive jaundice rats and liver regeneration after hepatectomy, providing a theoretical basis for the preoperative biliary drainage to hilar cholangiocarcinoma.
Methods: Builting the external biliary drainage animal model(obstruct 10 days), we divided all rats in four groups according to different drainaging times. 1, SO-Hx group: Normal rat hepatectomy group; 2, ED0-Hx group: External biliary drainage 0 days hepatectomy group; 3, ED2-Hx group: External biliary drainage 2 days hepatectomy group; 4, ED10-Hx group: External biliary drainage 10 days hepatectomy group. Observe the mortality of rats 15 days later,the liver functional rehabilitation and the ratio of residual liver weight/rat weight 7 days later. Detect the peak expression of PCNA and HGF mRNA in residual hepatic tissue by immunohistochemistry and RT-PCR technology.
Results: (1), The mortality in ED0-Hx group was very high(up to 40 percent), significantly higher than that in SO-Hx Group (0 percent). The mortality in ED2-Hx and ED10-Hx group decreased significantly, to 20 percent and 5 percent, but still higher than the SO-Hx group. (2), The total bilirubin level in ED0-Hx group was highest at 0h and still about 10 times higher than that in SO-Hx group 168h (7 days)later, the difference between the two groups were statistically significant (p<0.05) ; Aspartate aminotransferase also increased significantly and the recovery process was simillar to total bilirubin. Although the total bilirubin level in ED2-Hx group has dropped substantially at 0h, but the recovery process is similar to ED0-Hx groups. 168 h (7 days) later the total bilirubin still about 5 times higher than the that in SO-Hx group, the difference between the two groups were statistically significant (p <0.05); The total bilirubin and aspartate aminotransferase in ED10-Hx group are in a normal level during the 168h (7 days) after hepatectomy, Compared to the SO-Hx group there was not statistically difference (p>0.05). (3). The ratio of residual liver weight / rat weight 7 days after hepatectomy in SO-Hx was highest. Residual liver proliferation in the drainage groups significantly weakened, comparing to SO-Hx group the differences were statistically significant (p <0.05). Residual liver proliferation in ED2-Hx group was higher than that in ED0-Hx group and in ED10-Hx group it was highe than that in ED0-Hx group and ED2-Hx groups, comparing to eath other the differences were statistically significant(p<0.05). (4), The peak expression of PCNA and HGF mRNA increased after the external biliary drainage. The peak expression of PCNA and HGF mRNA in the external biliary drainage groups were lower than that in SO-Hx group, the differences were statistically significant (p<0.05). The peak expression of PCNA and HGF mRNA in ED2-Hx group was higher than that in ED0-Hx group, The peak expression of PCNA in ED10-Hx group was higher than that in ED2-Hx group, the differences between eath other were statistically significant (p <0.05).
Conclusion: 1. The hyperbilirubinemia caused by Biliary obstruction significantly inhibited the liver regeneration. liver function improved after external biliary drainage and the condition gradually recovered. Rat mortality reduced. 2. Although liver function inproved greatly in a short time after external biliary drainage, the liver regeneration was still in the inhibiting condition, the mortality was still high that was not suitable for the surgery. 3. It should be a long time drainage and after the liver function had been restored completely that the surgery for expanding hepatectomy can be safe.
引文
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