结直肠散发性腺瘤模型建立的探讨

目的　通过改进传统的DMH 结直肠癌肿瘤模型诱导方法,建立一个高效、稳定、实用的结直肠腺瘤模型,以用于散发性腺瘤生物学行为和分子生物学机制的研究。方法　选用SPF 级SD 雄性大鼠。诱导剂为1 ,22二甲基肼(DMH) 和PPAR2γ受体拮抗剂( GW9662) 。PPAR2γ受体激动剂为吡格列酮。试验分四组:阴性对照组、DMH 组、DMH + GW9662 组、DMH + GW9662 + 吡格列酮组。共观察12 周。试验结束取远端结直肠(全结直肠的1/ 2) 用福尔马林4°C 过夜固定,美蓝染色后实体显微镜下观察、计数息肉,并照相。全部息肉及微隆起粘膜进行组织学检查。结果　阴性对照组无腺瘤发生。DMH 组发现1 枚腺瘤,腺瘤诱导成功率为12. 5 %(1/ 8) ,荷瘤数为0. 125 (1/ 8) 。DMH + GW9662 组发现16 枚腺瘤,诱导成功率为87. 5 %(7/ 8) ,荷瘤数为2. 0 (16/ 8) 。DMH + GW9662 + 吡格列酮组发现5 枚腺瘤,诱导成功率为28. 6 %(2/ 7) ,荷瘤数为0. 714 (5/ 7) 。结论　DMH 联合应用GW9662 可以在短期内成功诱导大鼠结直肠腺瘤。该模型较单纯DMH 诱导的大鼠结肠癌和畸变隐窝灶模型更具实用价值。

Establishment of Animal Model Sporadic Colorectal Adenoma

Objective 　To build an economical ,effective and stable new experimental animal model of spo2 radic colorectal adenoma based on t raditional DMH2induced colorectal carcinoma model. The new animal model can be used to investigate the biological behavior and molecular mechanism of adenomas. Methods 　 Male Sprague2Dawley rat s were chosen in this study. Carcinogenic agent was DMH. GW9662 was chosen as the antagonist of PPAR2γ. Agonist of PPARγ was pioglitazone. Thirty2seven rat s were randomly grouped into four groups , named as negative cont rol group ,group DMH ,group DMH + GW9662 and group DMH + GW9662 + Pioglitazone. The experiment period was 12 weeks. At the end of experiment ,all rat s were sacrificed by euthanasia. Half of the distal colorectum was taken and immersed in formalin at 4 ℃overnight ,and then recorded the polyp s by anatomic microscope when stained by methylene blue. Pho2 tos of polyps were taken with high resolution digital camera and reversal film. All polyps and some flatten risen mucosa were verified by histology. Results 　There were no polyp s found in negative cont rol group. One adenoma was found in Group DMH. The incidence of adenoma was 12. 5 % (1/ 8) ,and the adenoma load was 0. 125 (1/ 8) . In Group DMH + GW9662 ,16 adenomas were found in all 8 rat s. The incidence of adenoma was 87. 5 % (7/ 8) ,and the adenoma load was 2. 0 (16/ 8) . The incidence of adenoma and the ade2 noma load in Group DMH + GW9662 + Pioglitazone were 28. 6 % (2/ 7) ,0. 714 (5/ 7) respectively. Conclu2 sion 　The combination of DMH and GW9662 can induce rat colorectal adenoma efficiently in a short ex2 periment period. This animal model can be used in colorectal adenoma and pre2cancerous lesions related researches and have more advantages compared with t raditional DMH induced colorectal carcinoma model and ACF model.