Objective To investigate the correlation between orexin A and the serine proteinase inhibitor vaspin in obese rats with insulin resis⁃tance(IR)induced by high⁃fat diet and elaborate the possible action mechanism of orexin involvement in fat metabolism in IR pathological process. Methods A total of 75 4⁃week⁃old male Sprague⁃Dawley rats were randomly divided into the normal dietary group(NC group,n=20)and the high⁃fat dietary group(HF group,n=55)to establish the model of obese rats with IR,the euglycemic insulin clamp technique was used to determine re⁃lated indicators of insulin resistance and lipid metabolism. The rats were treated with orexin A(1×10-8⁃1×10-6 mol/L)by hypodermic injection. The serum levels of orexin A and vaspin in rats were detected with enzyme linked immunosorbent assay. Results After 6 weeks of high⁃fat diet,the se⁃rum glucose,insulin,TC,TG and LDL⁃C were increased significantly in HF group than in NC group,while GIR60~120 in obese rats was decreased significantly[(16.31 ± 1.54)vs(30.22 ± 2.76)mg/(kg · min),P<0.05]. The serum vaspin level was increased 177.08%in HF group compared with NC group(P<0.05). With hypodermic injection of orexin A(1×10-8 mol/L,1×10-7 mol/L and 1×10-6 mol/L),the levels of serum vaspin in⁃creased 25.00%,68.75%,and 120.83%in NC group and increased 7.52%,24.06%,and 40.60%in HF group. There was a positive correlation be⁃tween vaspin and orexin A,glucose,insulin,TC,TG,and LDL⁃C(r1=0.482,P1=0.02,r2=0.515,P2=0.02,r3=0.303,P3=0.04,r4=0.388,P4=0.03,r5=0.255,P5=0.04,r6=0.253,P6=0.04)and a negative correlation between vaspin and HDL⁃C(r=-0.226,P=0.04)in obese rats with IR. Conclusion High⁃fat diet can induce insulin resistance and obesity in rats,and orexin A is closely correlated to vaspin in obese rats with insu⁃lin resistance. Orexin A increases serum vaspin expression and thus involves in onset of insulin resistance in obese rats.%目的：分析胰岛素抵抗（IR）肥胖大鼠体内增食欲素A（orexin A）与脂肪组织特异性丝氨酸蛋白酶抑制剂（vaspin）的相关性，阐明IR病理过程中orexin参与脂肪代谢的可能作用机制。方法4周龄SD雄性大鼠75只，随机分为正常饮食（NC）组（n=20）和高脂肪膳食（HF）组（n=55），建立IR肥胖大鼠模型，钳夹技术评定IR及脂代谢相关指标。大鼠皮下注射orexin A（1×10-8~1×10-6 mol/L），用酶联免疫吸附法检测血清orexin A和vaspin。结果（1）喂养6周后，与NC组比较，HF组大鼠血糖、胰岛素、TC、TG、LDL⁃C均增高（P均<0.05）；与NC组比较，GIR60~120降低[（16.31±1.54）vs（30.22±2.76）mg/（kg·min），P<0.05]；（2）HF组较NC组血清vaspin水平增加177.08%（P<0.05），NC组皮下注射orexin A（1×10-8，1×10-7，1×10-6 mol/L），NC组大鼠血清vaspin分别增加25.00%、68.75%、120.83%，HF组大鼠血清vaspin分别增加7.52%、24.06%、40.60%；（3）IR肥胖大鼠vaspin与orexin A、血糖、胰岛素、TC、TG、LDL⁃C呈正相关（r分别为0.482、0.515、0.303、0.388、0.255、0.253，P=0.04），与HDL⁃C呈负相关（r=-0.226，P均<0.05）。结论高脂膳食诱导的IR肥胖大鼠机体内orexin A与vaspin密切相关，orexin A增强vaspin的表达，进而参与肥胖大鼠机体内IR的发生。
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