再生途径干预对大鼠扩大肝切除术后生存的影响

Effects of interfering liver regeneration pathways on rat survival after extensive hepatectomy

目的观察抑制环氧合酶-2（COX-2）和Kupffer细胞对大鼠扩大肝切除术后生存的影响。方法大鼠行可耐受扩大肝切除手术后分别或联用NS-398和氯化钆，观测术后存活状态、余肝增重、血清转氨酶（ALT）和肝内增殖细胞核抗原（PCNA）水平。结果大鼠肝切除安全限量为85％，氯化钆和联合用药组术后7d存活率各为30％。术后2d氯化钆组肝增重比率为（1．23±0．21）％，高于单纯手术组的（0．95±0．08）％（P〈0．05），肝PCNA^＋细胞比例以氯化钆组最高[（88．56±4．08）％]，NS-398组最低[（20．95±8．54）％]，组间差异有统计学意义（P〈0．05）。氯化钆及联合用药组ALT增高。结论扩大肝切除早期抑制COX-2仅肝细胞增殖延迟，抑制Kupffer细胞虽肝再生增强，但肝毒性不利于大鼠存活。

Objective To investigate the effects of inhibiting cyelooxygenase-2 （COX-2） or/and Kupffer cells on rat survival and liver regeneration after extensive hepateetomy. Methods Healthy SD rats were treated with NS-398 or/and gadolinium chloride （ GdC13 ） 1 h after undergoing extensive hepateetomy. Rat survival rate, remnant liver growth, serum ALT and proliferating cell nuclear antigen （PCNA） immunoreactivity in the liver were detected on the postoperative day 2 and 7. Results The maximum size was 85% for safe live resection in SD rats and the survival rate was decreased to 30% in rats treated with GdC13 （GdC13 group） and GdC13 combined with NS-398 （GdClJNS-398 group）. On the day 2 after surgery and treatment, remnant liver regeneration ratio in GdC13 group was （1.23 ±0. 21 ）% , significantly higher than that in vehicle group [ （ 0. 95 ±0. 08 ） %, P 〈 0. 05]. Immunohistochemical analysis for PCNA revealed that hepatoeyte proliferation was enhanced by GdC13, but it was retarded by NS-398. In addition, serum ALT level was higher in GdC13 and GdC13/NS-398 groups than in the other two groups. Conclusion Inhibition of COX-2 suppressed early liver regeneration without affecting rat survival after extensive hepatectomy, whereas Kupffer cell depletion resulted in toxic effect on the remnant liver and increased postoperative mortality, though it enhanced early liver regenerative response.