【作者】 苏小华； 邓俊成； 田雨光； 那顺巴雅尔； 吕明； 江霞； 顾为望；

【Author】 Su Xiao-hua;Deng Jun-cheng;Tian Yu-guang;Na-shun-ba-ya-er;Lv Ming;Jiang Xiang;Gu Wei-wang;Laboratory Animal Center of Southern Medical University;Laboratory Animal Center,Guangdong Medical University;Dongguan Songshan Lake Pearl Laboratory Animal Science and Technology Co., Ltd.;

【机构】 南方医科大学实验动物中心； 广东医科大学实验动物中心； 东莞松山湖明珠实验动物科技有限公司；

【摘要】 目的:采用巴马小型猪作为实验对象,通过N-乙基-N-亚硝基脲(ENU)诱变剂筛选建立大型哺乳动物基因突变模型和人类疾病动物模型。方法:对巴马公猪阴囊部位注射85mg/kg剂量体重的ENU,利用ENU的作用对其精子进行诱变育种,获得一头血糖偏高的种公猪。通过近亲繁殖的方式,经过数代净化,建立高血糖家系。结果:G1代2907种公猪24个月空腹血糖持续6.3mmol/L水平以上,G5代3-6月龄餐前血糖平均值为7.48 mmol/L。静脉给糖实验显示2907和1只G5代达到糖尿病检测标准,2只G5代达到糖尿病前期检测水平。G5代3月龄于正常对照组相比生理生化指标中CHOL、HDL-CH、LDL-CH和体重高血糖组高于正常组(p﹤0.05),血糖相关指标INS、FMN和C肽均无明显差异。对猪的肝脏、胰脏和皮肤组织切片进行了HE染色,显微镜观察结果显示选育组胰岛组织中胰岛团个数减少,且团内细胞数量减少,分泌管病变程度介于对照组和STZ组,符合近1年的血糖测试结果。结论:已初步建立巴马小型猪高血糖家系,推测经过进一步的选育有希望建立小型猪新品系。更多还原

【Abstract】 Bamamini-pigs were used as the experimental objects in this research, and large mammalian gene mutation models and animal models of human diseases would be screened and established through mutagen ENU.In the screening process, fasting blood-glucose of breeding boars were monitored regularly, and the hyperglycemic breeding boars would be picked out.A stable hyperglycemic family was established by the way of inbreeding and several generations of purification. The main research contents of this paper:(1)The mutagen ENU with the dose of 85 mg/kg was injected directly in scrotum site of 12 G0 Bamamini-pigs breeding boars, after which 6 Bama mini-pigs boars that can provide mutagenic semen. Now, a 2907 family with inherited high blood glucose has been established, among which 2907 breeding boar keeps fasting blood glucose at the level of 6.3 mmol/L for 25 months(normal fasting blood glucose of Bama mini-pig is 2.0-3.5 mmol/L). The average blood sugar was 7.48 mmol/L in 3-month-old G5. Intravenous glucose test showed that 2907 and G5 generation met the criteria for diabetes mellitus.(2)The average values of PLT, TG and TP of the hyperglycemia group were lower than those of the normal group, while the TBLT of the hyperglycemia group were higher than that of the normal group.There were statistically significant difference in indexs of TC, HDL-CH, LDL-CH and body weight between the two groups in 3-month-old G5(p﹤0.05).The average values of INS, FMN and C-Peptide had no statistically significant difference between the two groups in G5(p﹥0.05).(3)The liver, pancreas and skin tissue sections of 9 pigs were stained with HE. Microscopic observation showed that the normal group’s islet showed an oval shape and a lot of cells with the glands closely together.The results were observed a transient increase in blood glucose after STZ treatment, insulin structural damage, extreme reduction of islet β cells. The experimental group’s blood glucose was between the normal and STZ groups. The HE observation showed that the islet were not normal. The number of islet β cells also reduced. Islet damage was lower in the STZ group, but the results were consistent with our expectations. The increase blood glucose and pathological changes of pancreas revealed that our design was feasible.In general, a 2907 family with inherited high blood glucose has been established, among which result in metabolic disorder, especially in glucose and lipid metabolism and Islet Cells.更多还原