门静脉分支结扎后门静脉压力变化与肝再生的关系

Relationship between portal vein pressure and liver regeneration after portal branch ligation in rats

目的探讨90％门静脉分支结扎后大鼠门静脉压力变化与肝再生的关系。方法45只雄性SD大鼠行90％门静脉分支结扎术，其中5只进行假手术作为对照。观察不同时相点门静脉压力和非结扎侧肝脏质量变化，光学显微镜下观察非结扎侧肝细胞的形态学变化，免疫组织化学方法检测未结扎侧肝细胞的增殖细胞核抗原（PCNA），TUNEL法检测未结扎侧肝细胞的凋亡情况，并进行定量分析。采用Pearson相关分析和t检验分析数据。结果95％（38／40）的大鼠存活。结扎侧肝叶进行性萎缩，非结扎侧肝叶占全肝质量的比例随时问推移而增加，12h内增加较缓慢，仅为10．75％；而1～5d则增加速度明显加快，达到27．57％；7～28d达到平台期，缓慢增加到32．37％。术前门静脉压力为（9．1±1．8）etnH2O（1cmH2O=0．098kPa）；结扎后立即升高，12h达到高峰（15．8±2．7）CmH2O，与术前比较差异有统计学意义（t=6．847，P〈0．05）；1～28d由（13．6±2．3）cmH2O逐渐下降为（9．3±2．0）CmH2O。术前大鼠PCNA阳性细胞计数为7％±3％，术后12h至3d由14％4-5％上升至21％4-6％，第5天达到高峰为26％±7％，与术前比较差异有统计学意义（t=9．129，P〈0．05），随后逐渐恢复正常。TUNEL法检测结果显示，术前大鼠肝脏和术后各时相点大鼠未结扎侧肝脏仅见极少量凋亡细胞。大鼠门静脉压力与非结扎侧肝叶肝细胞PCNA的表达在术后1、3、5d呈正相关（r=0．913，0．896，0．908，P〈0．05），在术后14d时相点呈负相关（r=-0．926，P〈0．05）。结论大鼠90％门静脉分支结扎术后，引起未结扎侧肝细胞的活跃再生，再生后的肝脏可恢复原来的质量；肝再生以肝细胞增殖加速为主，而非肝细胞凋亡减少；门静脉压力变化在肝再生过程中可能发挥重要作用。

Objective To investigate the relationship between portal vein pressure and liver regeneration after 90% portal branch ligation in rats. Methods Forty-five male SD rats underwent 90% portal branch ligation （ including 5 rats underwent sham operation）, and then the changes of portal vein pressure and weight of unligated hepatic lobes were detected. The morphological changes of hepatocytes of the unligated hepatic lobes were observed under a light microscope. Proliferative cell nuclear antigen （PCNA） index was detected by immunohistochemistry, and hepatocyte apoptosis of the unligated hepatic lobes by TUNEL method. All data were analyzed by Pearson rank correlation analysis and t test. Results Thirty-eight out of 40 rats survived （95%）. The ligated hepatic lobes diminished progressively, whereas the unligated hepatic lobes regenerated. Preoperative portal vein pressure was （9.1 ± 1.8 ）cm H2O （1 cm H2O = 0. 098 kPa） , and it was increased significantly shortly after the ligation and reached （ 15.8± 2.7） cm H2O12 hours later （ t = 6. 847, P 〈 0.05 ）. The portal vein pressure decreased from （ 13.6± 2.3）cm H2O at day 1 to （9.3 ±2.0）cm H2O at day 28. Preoperative positive PCNA index was 7%±3%, which was significantly lower than 14% ±5% at postoperative 12 hours, 21% ±6% at day 3 and 26% ±7% at day 5 （t =9. 129, P 〈 0.05 ） , and it began to return to normal at day 5. Few apoptotic hepatocytes were observed in preoperative liver tissue and unligated hepatic lobes. The expression of PCNA in unligated hepatic lobes and portal vein pressure had apositive correlation at postoperative day 1, 3, 5 （r = 0. 913,0. 896, 0. 908, P 〈 0.05 ） and a negative correlation at postoperative day 14 （r = - 0. 926, P 〈 0.05）. Conclusions The regeneration of hepatocytes in unligated hepatic lobes is activated after 90% portal branch ligation, and the regenerated liver compensates the weight loss of the ligated hepatic lobes. Liver is regenerated mainly by speeding hepatocyte proliferation rather than reducing hepatocyte apoptosis. Changes of portal vein pressure may play an important role in liver regeneration.