Engum S A, Sidner R A, Miller G A, Galliani C, Grosfeld J L
Department of Surgery, Indian University School of Medicine, Indianapolis.
J Pediatr Surg. 1993 Mar;28(3):411-7; discussion 417-9. doi: 10.1016/0022-3468(93)90241-c.
Although cisplatin is widely used in the treatment of liver tumors, little information is available concerning its effect on liver regeneration. This report evaluates the effect of cisplatin on liver regeneration after hepatectomy (HPx). One hundred sixty male Sprague-Dawley rats were placed into five experimental groups following 70% hepatectomy. Group I (untreated controls, n = 32) received 0.9% saline intraperitoneally (IP); group II (n = 31), cisplatin 4 mg/kg IP; group III (n = 36), cisplatin 10 mg/kg IP; group IV (n = 34), cisplatin 20 mg/kg IP; and group V (n = 27), doxorubicin 6 mg/kg intravenously (IV). Five additional sham groups underwent celiotomy without hepatectomy (n = 106) followed by the above treatment protocols. Liver regeneration was evaluated by liver weight, DNA incorporation measured by tritiated thymidine (3H-TdR), and quantitative image analysis (QIA) of hepatic nuclei at 18, 24, 36, 48, and 72 hours, and 5 days postoperatively. 3H-TdR incorporation peaked at 36 hours and was similar in hepatectomized controls group I (404 +/- 110 counts per minute [CPM]/mg liver weight) and cisplatin-treated rats (groups II to IV) (P > .05, ANOVA). All sham groups were similar to controls. QIA of feulgen-stained touch preps identified polyploid, stem line, and proliferating nuclei in both controls and treated groups. At 36 hours, QIA showed differences in mitotic status of sham, control, and adriamycin-treated HPx rats, consistent with 3H-TdR incorporation. In contrast, although cisplatin-treated rats receiving 4 mg/kg showed proliferating nuclei, QIA demonstrated decreasing hepatocyte proliferation with higher doses of cisplatin (10 mg/kg, and 20 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
尽管顺铂广泛应用于肝肿瘤的治疗,但其对肝再生的影响却鲜有报道。本报告评估了顺铂对肝切除术后肝再生的影响。160只雄性Sprague-Dawley大鼠在接受70%肝切除术后被分为五个实验组。第一组(未治疗对照组,n = 32)腹腔注射0.9%生理盐水;第二组(n = 31),腹腔注射4 mg/kg顺铂;第三组(n = 36),腹腔注射10 mg/kg顺铂;第四组(n = 34),腹腔注射20 mg/kg顺铂;第五组(n = 27),静脉注射6 mg/kg阿霉素。另外五个假手术组接受剖腹术但不进行肝切除术(n = 106),随后按照上述治疗方案进行处理。通过肝重量、用氚标记胸腺嘧啶核苷(3H-TdR)测量的DNA掺入量以及术后18、24、36、48、72小时和5天时肝细胞核的定量图像分析(QIA)来评估肝再生情况。3H-TdR掺入量在36小时达到峰值,肝切除对照组第一组(404±110计数每分钟[CPM]/mg肝重)和顺铂处理组大鼠(第二组至第四组)相似(P>.05,方差分析)。所有假手术组与对照组相似。对福尔根染色的触片进行QIA分析,在对照组和处理组中均识别出多倍体、干细胞系和增殖细胞核。在36小时时,QIA显示假手术组、对照组和阿霉素处理的肝切除大鼠的有丝分裂状态存在差异,与3H-TdR掺入情况一致。相比之下,尽管接受4 mg/kg顺铂处理的大鼠显示有增殖细胞核,但QIA表明随着顺铂剂量增加(10 mg/kg和20 mg/kg),肝细胞增殖减少。(摘要截断于250字)