两种大鼠肝癌肝移植模型的建立及其对比分析

Establishment and comparison of two rat models of liver transplantation for hepatoceilular carcinoma

目的建立大鼠“种植性肝癌”和“诱发性肝癌”肝移植模型，并进行对比分析。方法将腹水型Walker-256癌肉瘤Wistar大鼠的肿瘤接种到SD大鼠肝左外叶，建立大鼠“种植性肝癌”模型后建立同系SD大鼠肝癌肝移植；使用二亚基亚硝胺建立SD大鼠“诱发性肝癌”模型后建立同系SD大鼠肝癌肝移植模型。对比分析两个肝癌肝移植模型中大鼠肿瘤形成、术后存活时间、对免疫治疗的耐受及肿瘤复发规律等。结果接种瘤块后2周，所有SD大鼠的肝脏均形成局限性生长的肿瘤，此时适宜作为受鼠接受肝移植，移植后3周内死亡4只，存活率为84％（21／25）；移植后第4、5、6和7周肺转移瘤的发生率分别为0、20％（1／5）、60％（3／5）和66．7％（4／6）。接种瘤块后3周，大鼠肝脏肿瘤呈弥漫性生长，不宜作为受鼠。经移植时“病肝”的病理检查，诱癌后75d（75d组）接受肝移植的受鼠肝肿瘤形成率为10％（1／10），95d组为80％（8／10），115d组为100％（10／10），对照组（诱癌75d，并使用了环孢素A）组为0，其中75d组受鼠存活时间最长，与其他组比较，差异均有统计学意义（P〈0．05），术后长期存活的受鼠均未发生肿瘤转移。结论“诱发性肝癌”肝移植模型难以兼顾肿瘤形成及术后存活，不是理想的实验模型，而“种植性肝癌”肝移植模型的应用价值取决于瘤株的成瘤潜能及其生物学行为。

Objective To compare the validity and reliability of diethylnitrosamine （DEN）- induced and intrahepatic-tumor-implanted hepatoma related to tumor recurrence after liver transplantation for hepatocellular carcinoma. Method A small and superficial incision into the liver of SD rats was made, and 0. 5-1.0 mm cube of walker-256 carcinosarcoma fragments was implanted into the liver incision. At week 2, Syngeneic OLT was performed with the cuff technique without re- arterilization. Hepatoma was also induced by DEN administered continuously through the drinking water, in which survival and metastasis were analyzed. Furthermore, the comparisons were performed related to formation of tumor, postoperative survival, tolerability of imrnunosuppression and tumor recurrence for OLT for DEN-induced or intrahepatic-implanted hepatoma. Results The presence of solitary tumor was 100% at week 2 in the intrahepatic tumor implantation （IHTI） model, and the OLT of recipients was done. The 3-week survival rate after OLT for IHTI was 84% （21/25）, and the incidence of lung metastases was 0 （0/5）, 20%（1/5）, 60% （3/5） and 67% （4/6） at week 4, 5, 6, 7 respectively. The tumor from DEN was found in 1/10, 8/10, 10/10, and 0/10 in 75-day, 95-day, 115-day and 75-day＋ CsA groups, respectively. A significant difference in postoperative survival was observed between group 75-day and 95-day group （log rank = 5. 348,P = 0. 021） ; also between 75-day group and ll5-day group （log rank = 9.820, P = 0.002）. No recurrence was presented in the transplants from DEN. Conclusion Hepatoma induced by DEN is not suitable to study recurrence after OLT for HCC, due to highly variable outcome from same carcinogenesis pattern. The value of IHTI model for this purpose was greatly associated with biological behaviors and tumor-initiating ability of cancer cells.