摘要
随着临床营养支持的进一步发展、应激条件下机体物质代
谢研究的深入以及对代谢支持、代谢调理等概念的认识，重组
人生长激素（recombinant human growth hormone，rhGH）的临床
及实验研究已基本肯定了其在促进外科手术后病人蛋白质合
成，减轻分解代谢，改善氮平衡，动用体脂，增加瘦组织群等
方面的作用。然而，有资料表明各种生长因子既是促进生长的
正常因子，亦可能具有促进肿瘤增生、诱发组织癌变的潜能。
因此肿瘤病人术后能否使用rhGH存有争议。
大肠癌是常见的消化道恶性肿瘤之一，实施治愈性手术后
仍有较高的肝转移发生率。术后为改善氮平衡而使用的rhGH对
大肠癌肝转移瘤是否有影响？此类患者术后使用rhGH是否安
全？其促进蛋白质合成和细胞生长的作用对转移瘤有无影响？
已成为关注的问题。
一、结肠腺癌肝转移动物模型的建立 采用BALB/c小鼠，
经脾脏注入指数生长期的小鼠结肠腺癌细胞（CT26）悬液
0.1ml，含细胞1×10~6个，保留脾脏。观察接种后小鼠生存期，
分别于接种后第7、10、15天处死后及自然死亡后解剖观察腹
腔内肿瘤生长情况，留标本作病理检查和流式细胞术（FCM）
倍体检测。结果：小鼠平均自然生存时间为（18.2±1.8）天，
尸解发现接种动物肝脏表面均有灰白色转移结节形成，脾脏上
有肿瘤，其他脏器未见转移病灶。病理示肝转移瘤细胞与脾脏
肿瘤细胞结构相似，符合低分化腺癌的特征。FCM示肝转移瘤
D 阐人（陡杠人‘广1贝D／j‘小j1E义
I 为四倍体肿瘤，与＊D6细胞倍体检测结果一致。楞示经脾捂种
D 厂T？斤昙栓六夕士肠疤月干姑孩的石丁会子丹抵士召开［J
乙 l二口刀二大乏N 3占 fJ刃夕函厂丁斗亨呛日J q菲叨刁刃个关】C。
D 二 矾官古的人硅足褂吾／个门Nl 对，1、富灶隔晌疤盯杜北
D——、们Dfu主主比八上＊W乐＼nMnJ 川’I”氏G州0水溉OD沾忖
D 淄的衫”问 遏工功脚偎尘石一返用乙方刀闪姐，头马贫进卜于口反卜
D．－注射叩川ZIW2，对照组度下注射生理盐水，权。。7夫。。驮狮
l－机抽取部分小鼠于瘤细胞接种 2周后处死，观察肝转移瘤 4k
l 目、肝脏重量，并采用流式细胞术作肿瘤细胞 DNA周期分析，
D 其余小鼠待其自然死亡，记录生存期n结果：GH纽小鼠体亩显
I 萎谗力Of＿n＜）止和舷兰界久／＜d66＋77门。AS日克立一F
咱。自川。＼厂’ru刀JJ，六——W，oJ了口 ＼＊q．＊0上二．二巨／扮L 明工L向J
D7rf日g州1 d7＊0十d＊飞｝。厂JPrru门1、而如，卜冒n干片大斗之乃员末卉日
M54f号、牛存期吊天。轿计学姜异jmpo气、．nH4日 对日召夕日
l 肝脏重量分别为（3．53士二．20）2、门．20士0．77）2。DNA细胞周
D 期分析显示＊H组分裂期（Gl期）细胞百分比门97土4．S］）
D 高于对照组（5．40士 1．95，P＜0．05），肿瘤细胞增殖指级（PI）
D 门Hk日数佰1刀“十47只】烹干对昭壬日JN“＋9二1 厂＼urn、D
DUIW 十人l且＼上／．UU“十二0／问j 川尸X3且＼二二．OO上o．二1，厂夕U．U二J。D
D 提示1llGI刁促使肿瘤细胞进入分裂期，认为肿瘤病人女。开。庄他抗D
肿瘤治疗广尺号僻劳单柱修用巾门厂J
三、研冗腹）jR腔化疗及耳关苔叫吏用 山GH g寸小鼠结肠痛肝转l
才多的衫响 卜I活淳工肝转烙擒型后阻机分为飞g日、单幼．仆；疗卓日小D
鼠每日腹膜腔注射 5．F［l 20lllMig：联今胡甚日方下诈射 h门H D
刀＊怔，同时月夏月莫腔注射 5．rll二OITh邮q：对昭勿权以叶刃故水今 D
力IJ寸丁／义 卜 剔吴腥压射，y了枉力7大。二）舌l后母组］预才儿J由奴部分］
动物处死，观祭肝转移情况；采用流式细胞术吓CM）行DNA D
细胞周期分析，其余动物待自然死亡以比较生存期。结果，联D
合组血浆总蛋白明显高于化疗组和对照组（P＜0川）＿与对8纠po
相比，化疗组和联今纽的肝转格廷牛率兹伦．．枯稳痫汾日动D
少，｝f ）J压更重明显较低（P＜0．05），小鼠生存期延长沂一供 l
〔严们＊） 股令幻肿癌细脉固加十静；V加JrtAI地）细晌百D
多＞止匕 87D土二了）高干土二伽。两套向。；f77士 R 2 7R q＋R Al
41
南京医科大学硕十学位论文D
（P＜0．05入 肿瘤细B赡殖指数m）在对照、化疗、联合组中、T
分别为22．7士8．3，ZI．
Background. The beniflcial effects of adrninistmtion of recombinant
growth homione (thGH) in sugical patients have been confirmed in
clinical and expeiimental studies. The administration of rhGH increases
protein sithesis ,reverse the catabolic response, improve nitrogen
balance ,preserve lean body mass and reduce adipose tissue mass. On the
other hand , papers also show that growth factors not only promote the
growth of normal tissue ,but also have the potence in increasing
proliferation of tumors ,inducing mutation of tissues. Contrnverse still
exists over the question whether IhGH could be used in patients with
cancer remains dispute.
Fairly high occurrence of hepatic metastases has been observed in
patients with colorectal cancer after radical operations. Whether the use of
rhGl I to imilprove nitrogen balance accelerates the growth of liver
metastases becomes deeply concerned. The safety of application of rhGH
in these patients has not been reported.
In this study, the effect of growth hormone and combined with
pemitoneal chemotherapy on the cieyelopment of hepatic metastases of
colonic adenocarcinoma in the mice his been evaluated.
Iart I.
Methods .To develop a colonic adenocarcinoma liver metastases model
thy expeiimental studies, BALB/c mice were selected to receive
intmsplenic injection of 0.1 ml solution containing I x 10~抍ells of colonic
adenocarcinoma cells(CT26) . The spleen was left intact The survival time
of animals was recorded. Animals were evaluated on the 7th ,IOth, 15th
days postinjection and full abdominal autopsy was performed ,respectively.
~11ie tumors of liver rnetastases were studied histologically and ploid of
kunor cells was determined by flow cytornetzy (FCM).The experiment
shows that the average survival time of animals was (18.2 ?1.8) days. All
animals inoculated with C1726 cell lines developed liver metastases.
Metastases to other organs were not observed. The pathological results
showed that tumor cells of liver rnetastases were poorly differentiated
colonic adenocarninoma. FCM indicated that tumors of liver metastases
were tetraphoid, as same as CT26 cell lines. It is concluded that
intmsplenic injection of CT26 cells is a reliable model for producing
colonic cancer liver metastases and should prove valuable in experimental
studies.
To study the effect of growth hormone on hepatic rnetastases of
colonic adenocaninorna, twenty-eight established hepatic metastases mice
were divided randomly into GH lreated and control groups. In GH group
animals, recombinant human growth hormone (rhGH) was injected
subcutaneously with 21U/kg d for seven days. Instead of rhGH~ normal
saline was used in the control group. Two weeks after the last
injection ,eight animals in each group were sacrificed, the tumor number of
liver metastases and weight of liver were counted and cell cycle of tumor
DNA was determined by flow cytornetly (FCM).The rest of animals in the
two groups were fed till death in order to observe survival time.
7
Results. In Gil group the body weight of animals increased rapidly.
(P<0.05) and the level of serum total protein (54.7 ?2.2)g/L was higher
than that of control group(47.2 ?4.9)g扡 significantly(P<0.0 I). No
significant differences were observed in the number of liver metaslases,
liver weight and survival time between the two groups (P>0.05). DNA cell
cycle analyses showed that the pereentage of G2/1
引文
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