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目的:通过化学遗传学技术构建胰升糖素样肽1(GLP-1)神经元可控性模型大鼠，并观察GLP-1神经元兴奋性的变化对食欲的调控作用。方法:将15只大鼠分为绿色荧光蛋白(GFP)组、HM3D组和HM4D组，每组5只。分别在3组大鼠的孤束核区域注射不同组合的腺相关病毒(rAAV)，GFP组在孤束核区域注射rAAV-GLP-1-cre和rAAV-GFP-dio；HM3D组在孤束核区域注射rAAV-GLP-1-cre和rAAV-HM3D-mCherry-dio；HM4D组在孤束核区域注射rAAV-GLP-1-cre和rAAV-HM4D-mCherry-dio。通过观察腹腔注射不同剂量N-氧化氯氮平(CNO)后大鼠的摄食行为和体重变化来筛选其最佳剂量。通过与腹腔注射生理盐水进行比较来确认GLP-1神经元的可调控性。观察大鼠处死前30 min注射CNO后大鼠孤束核区域GLP-1神经元的激活数量及下丘脑POMC神经元的表达。结果:各组大鼠孤束核区域内GLP-1神经元均成功被标记，CNO注射剂量为1mg/kg时，HM3D组大鼠摄食减少(n P＝0.021)，而HM4D组大鼠摄食增加(n P＝0.002)。而注射剂量为0.5 mg/kg和3 mg/kg时均未出现此效应。免疫荧光结果显示，HM3D组孤束核中GLP-1神经元的兴奋性高于GFP组(n P＝0.022)，GFP组高于HM4D组(n P＝0.049)。腹腔注射CNO后HM3D组大鼠孤束核区域内的GLP-1神经元及下丘脑的POMC神经元表达也高于HM4D组(n P＝0.003)。n 结论:通过化学遗传学技术在大鼠孤束核内注射不同组合的rAAV能够成功建立GLP-1神经元可控性模型大鼠。1 mg/kg的CNO剂量能够有效激活或抑制该神经元，从而产生调控食欲的效应。“,”Objective:To conduct a glucagon like peptide-1(GLP-1)controllability model rat by chemical genetics, and observe the impact of GLP-1 neuron excitability on appetite.Methods:Fifteen rats were evenly divided into Green fluorescent protein(GFP)group, HM3D group, and HM4D group. Various combinations of adeno-associated virus(rAAV)were injected into the nucleus tractus solitarius(NTS). rAAV-GLP-1-cre and rAAV-GFP-dio were administered in rats of GFP group. The rats of HM3D group were injected with rAAV-GLP-1-cre and rAAV-HM3D-mCherry-dio while rAAV-GLP-1-cre and rAAV-HM4D-mCherry-dio were injected in rats of HM4D group . The optimal dose of clozapine N-oxide(CNO)was selected based on feeding behavior and body weight changes of rats after intraperitoneal injection of different doses of CNO. The controllability of GLP-1 neurons was confirmed by comparing with intraperitoneal injection of saline. The number of activated GLP-1 neurons in the NTS area and the expression of POMC neurons in the hypothalamus were detected 30 minutes after CNO injection.Results:GLP-1 neurons in the NTS area of rats were successfully labeled. The rat of HM3D group revealed a decrease in food intake(n P=0.021)while the rat of HM4D group showed an increase(n P=0.002), when given 1 mg/kg of CNO, no changes at the dose of 0.5 mg/kg and 3.0 mg/kg. Immunofluorescence showed that the activity of GLP-1 neurons in NTS of GFP group was lower than that of HM3D group(n P=0.022), and higher compared with that of the HM4D group(n P=0.049). The expression of GLP-1 neurons in NTS and POMC neurons in the hypothalamus of the HM3D group after intraperitoneal injection of CNO was also higher than that in the HM4D group(n P=0.003).n Conclusion:Using chemical genetics technology, GLP-1 controllability model rat could be successfully established via injecting varying combinations of rAAV into the NTS area of rat. Injection of 1 mg/kg CNO can effectively activate or inhibit the neuron to regulate appetite.