裸鼠糖尿病合并肺腺癌模型建立

Establishing models of Nude mice of diabetes combined with lung adenocarcinoma

目的 糖尿病和肺癌均为常见病、多发病,发病率逐年升高,糖尿病合并肺癌的发病率亦明显升高。本研究通过制备裸鼠糖尿病、肺腺癌和糖尿病合并肺腺癌模型,探讨糖尿病和肺癌之间的关系。方法 选择4~6周龄雄性裸鼠54只,体质量18~22g,随机分为正常对照组（12只）、糖尿病组（12只）、肺腺癌组（15只）和糖尿病合并肺腺癌组（15只）4组。制备糖尿病模型：裸鼠腹腔内注射链脲佐菌素（STZ）150mg/kg（根据预实验结果得出）。制备肺腺癌模型：收集培养的A549细胞,计数,调整细胞悬液浓度为1×107个/mL,以每只0.2mL接种于裸小鼠右侧腋窝皮下,正常对照组腹腔内及腋下均注射等量生理盐水。待糖尿病造模成功并稳定后,再在裸鼠腋部皮下注射人肺腺癌细胞株,制备糖尿病合并肺腺癌模型。结果 裸鼠糖尿病、肺腺癌、糖尿病合并肺腺癌模型均造模成功,其中体质量、血糖在正常对照组、肺腺癌组、糖尿病组及糖尿病合并肺腺癌组开始时差异无统计学意义;造模成功后,肺腺癌组、糖尿病组及糖尿病合并肺腺癌组体质量在放疗前、放疗后1和2个月明显低于正常对照组,P〈0.05;血糖在糖尿病组、糖尿病合并肺腺癌组明显高于正常对照组、肺腺癌组,P〈0.05;至放疗前,正常对照组、糖尿病组、肺腺癌组、糖尿病合并肺腺癌组各组自然死亡率差异无统计学意义,P〉0.05,均死亡1只。肿瘤标志物癌胚抗原（CEA）在肺腺癌组及糖尿病合并肺腺癌组放疗前后差异有统计学意义,P〈0.05;且明显高于正常对照组及糖尿病组,P〈0.05。结论 裸鼠糖尿病、肺腺癌和糖尿病合并肺腺癌模型的成功建立,为临床糖尿病、肺腺癌及糖尿病合并肺腺癌的治疗提供实验依据。

OBJECTIVE Diabetes and lung cancer are common and frequently-occurring disease. The incidence of the two kinds of diseases is increased. The incidence of diabetes combined with lung adenocarcinoma is significantly in creased. The aim of study is to establish models of diabetes, lung adenocarcinoma and diabetes combined with lung adenocarcinoma in nude mice to research the interaction between the two diseases. METHODS 54 experimental animals of 4 to 6 week-old male nude mice, weight 18-22 g, were selected and randomly divided into four groups：normal control group of 12, diabetes group of 12, lung adenocarcinoma of 15 and diabetes combined with lung adenocarcinoma group of 15. Two groups of diabetes models were firstly established, the other two groups were lung adenocarcinoma and normal con troi. Diabetes combined with lung adenocarcinoma group was secondly established after diabetes model had been success ful and stable in one of the two diabetes model groups. Diabetes models were made as followings：Intraperitoneal injection of streptozotocin （STZ） 150 mg/kg （derived according to the results of preliminary experiments） was made in nude mice, preparation of lung adenocarcinoma model：collection of cultured A549 cells, counting, adjust the concentration of the cell suspension of 1 X 107 mL-1 , taking 0.2 mL inoculated subcutaneously in right axillary of each nude mice in lung adenocar cinoma group and one of the diabetes group, and the other two groups were injected with normal saline in the same site. RESULTS Nude mice models of diabetes, lung adenocarcinoma and diabetes combined with lung adenocarcinoma were set up successfully. The weights and blood glucose levels in four groups were no difference at the beginning. The weights in groups of diabetes, lung adenocarcinoma and diabetes combined with lung adenocarcinoma were less than that in group of normal control,P〈0.05. The blood glucose levels in groups of diabetes and diabetes combined with lung adenocarcinoma were more than that in the groups of normal control and lung adenocarcinoma,P〈0.05. The mortality in four groups was no difference before radiotherapy. There was significant difference on tumor markers of carcinoembryonic antigen （CEA） in lung adenocarcinoma group and diabetes combined with lung adenocarcinoma group before and after radiotherapy （P〈 0.05） ,and significantly higher than that in normal control group and diabetes group （P〈0.05）. CONCLUSIONS The establishment of nude mice models of diabetes, lung adenocarcinoma and diabetes combined with lung adenocarcinoma is successful. This research can provide the basis for therapy of clinical patients with diabetes, lung adenocarcinoma, diabetes combined with lung adenocarcinoma.