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基于荧光标记迷走神经元转基因小鼠的袖状胃切除术动物模型建立 被引量:1

Establishment of sleeve gastrectomy model based on transgenic mice with fluorescently labeled vagal neurons
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摘要 目的建立基于迷走神经元荧光标记的高脂饮食诱导肥胖(DIO)小鼠和袖状胃切除(SG)小鼠模型。方法选取购自美国Jackson实验室10周龄健康的无特定病原体级Phox2b-Cre-tdTomato转基因小鼠。获得标记基因的小鼠随机分为两组,分别给予高脂饮食和正常饲料喂养,获得DIO小鼠。25只DIO小鼠依据随机数字表法分为3组分别接受袖状胃切除术(SG,10只),袖状胃切除-迷走神经离断术(SG+TV,10只)和假手术配对喂养(SH,5只)。观察围手术期(术后2、8、12周)各组小鼠体质量和空腹糖水平变化,免疫组织化学检查肠脑轴各器官迷走神经分布情况。计数资料采用t检验。结果各组Phox2b-Cre-tdTomato杂合子小鼠的胃、小肠、结状神经节与后脑区均可见红色荧光染色阳性表达。与SG小鼠相比,SG+TV组小鼠术后的胃、肠、结状神经节和后脑区荧光表达均减弱。术后12周,与SH组小鼠相比,SG和SG+TV小鼠术后的体重和血糖水平均有明显的下降趋势,且随时间延长下降幅度逐步增加,SG和SG+TV小鼠与SH小鼠相比体重和空腹血糖差别有统计学意义。3组小鼠体重分别为(56.7±4.4)、(24.5±7.7)、(36.0±3.3)g,空腹血糖分别为(9.1±0.1)、(4.1±0.4)、(5.8±0.4)mmol/L(t=4.652、4.025、16.050、10.240,P<0.01)。与SG组小鼠相比,SG+TV组小鼠在术后早期(8W内)体重和血糖水平未见明显差异,但8W后SG-TV组小鼠的体重和血糖的下降幅度有所缩小,体重下降(1.0±0.7)g,血糖下降(0.3±0.4)mmol/L,但差别无统计学意义(t=0.180、4.789,P>0.05)。SH组小鼠在术后12周体重和血糖水平基本恢复术前水平。在总体重丢失方面,SH小鼠在术后12周总体重丢失现象开始消失,而SG与SG+TV组在术后12周的总体重丢失分别为(24.3±6.8)g和(25.2±4.2)g;与SH小鼠[(3.8±0.8)g]比较,差异有统计学意义(t=4.031、7.131,P<0.01);术后12周,SG与SG+TV组的总体重丢失比例分别为(49.1±1.0)%和(49.2±1.1)%,与SH组小鼠[(6.2±0.9)%] Objective To establish a high fat diet-induced obesity(DIO)and sleeve gastrectomy(SG)model in mice with fluorescence labeling of vagal neurons.Methods Healthy,pathogen-free Phox2b-Cre-tdTomato transgenic mice purchased from Jackson laboratory,USA,were selected.Twenty-five 8-week-old Phox2b-Cre-tdTomato transgenic mice with fluorescence labeling of vagal neurons were fed on high fat diet,and randomly divided into three groups:SG group(n=10),Sleeve gastrectomy-truncal Vagotomy(SG+TV)group(n=10),Sham group(n=5).The body weight,fasting blood glucose during perioperative period were observed.The distribution of vagal nerve on every gut-brain axis organ were measured by IHC.T test was used for counting data.Results Using fluorescencestaining,the vagal neurons were demonstrated in the stomach,small intestine,ganglion and hindbrain area,while red fluorescence staining was decreased in the SG+TV group,compared to the SG group.12 weeks after surgery,compared with SH group of mice,the body weight and blood glucose level in the mice in SG and SG+TV groups declined obviously,and further declines gradually increased over time.The body weight of the mice in the three groups was(56.7±4.4),(24.5±7.7),(36.0±3.3)g,and fasting blood glucose was(9.1±0.1),(4.1±0.4)and(5.8±0.4)mmol/L,respectively(t=4.652,4.025,P<0.01).Compared with SG group mice,there was no significant difference in body weight and blood glucose level in the early postoperative period(within 8 weeks)in SG+TV group mice.However,after 8 weeks,the weight and blood glucose levels of SG-TV group mice were reduced to(1.0±0.7)g and(0.3±0.4)mmol/L,but the differences were not statistically significant(t=0.180,4.789,P>0.05).The weight and blood glucose levels in the SH group were basically restored to their preoperative levels 12 weeks after surgery.In terms of total weight loss,SH mice began to lose weight 12 weeks after surgery,while the total weight loss in SG and SG+TV groups was(24.3±6.8)g and(25.2±4.2)g,respectively.The difference was statistically significant
作者 张隆江 张新 张海 麻献华 张景辉 刘兆瑞 郑瑞 申晓军 印慨 Zhang Longjiang;Zhang Xin;Zhang Hai;Ma Xianhua;Zhang Jinghui;Liu Zhaorui;Zheng Rui;Shen Xiaojun;Yin Kai(General Surgery Department of Changhai Hospital affiliated to Naval Military Medical University,Shanghai 200082,China;Department of Pathology,Basic Medical College,Naval Military Medical University,Shanghai 200433,China)
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2020年第9期1742-1745,共4页 Chinese Journal of Experimental Surgery
基金 国家自然科学基金(81570766) 上海市自然科学基金(17ZR1438400)。
关键词 袖状胃切除术 模型 荧光标记迷走神经元 Sleeve gastrectomy Model Fluorescent labeling of vagal neurons
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