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目的:探讨下丘脑注射OXR-1选择性受体拮抗剂ACT-335827对肥胖大鼠代谢的效果。方法:通过高脂饮食建立肥胖大鼠模型,采用CODA 8通道高通量非侵入性血压系统(EMKA)测量血压;所有脂类都使用商品酶试剂盒和TOSHIBA-40FR全自动分析仪测量;空腹血糖采用葡萄糖氧化酶法;空腹胰岛素采用放射免疫法测定。肥胖大鼠出现代谢紊乱后,给予ACT-335827处理,检测大鼠体重、血压、脂肪、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、游离脂肪酸(NEFA)、瘦素、空腹血糖及空腹胰岛素等的变化。结果:与普通饮食组相比,经过10周高脂饮食,高脂饮食组大鼠体重显著升高(P<0.05),给予ACT-335827处理后,普通大鼠的体重、血压、脂肪含量、脂代谢等均无明显变化;与高脂饮食和高脂饮食加生理盐水处理组大鼠比较,高脂饮食加ACT-335827处理组肥胖大鼠的体重显著下降(P<0.05),腹部和附睾脂肪含量下降(P<0.05),低密度脂蛋白、甘油三酯、总胆固醇、瘦素水平下降(P<0.05),空腹血糖及空腹胰岛素也显著降低(P<0.05),但血压、肠系膜脂肪和肩胛棕色脂肪、高密度脂蛋白和NEFA无明显变化(P<0.05)。结论:ACT-335827对肥胖大鼠的代谢紊乱具有改善作用,对肥胖大鼠有一定的减肥作用。
Objective: To investigate the effect of hypothalamic injection of OXR-1 selective receptor antagonist ACT-335827 on the metabolism of obese rats. Methods: The obese rat model was established by a high-fat diet and blood pressure was measured by the CODA 8-channel high-throughput noninvasive blood pressure system (EMKA); all lipids were measured using a commercial enzyme kit and a TOSHIBA-40FR automatic analyzer; Blood glucose using glucose oxidase method; fasting insulin by radioimmunoassay. After metabolic disorder, obese rats were given ACT-335827 and the body weight, blood pressure, fat, triglyceride, total cholesterol, high density lipoprotein, low density lipoprotein, free fatty acid (NEFA), leptin, Blood glucose and fasting insulin and other changes. Results: After 10 weeks of high-fat diet, the body weight of rats in high-fat diet group was significantly increased (P <0.05). After treatment with ACT-335827, body weight, blood pressure, fat content, (P <0.05). The body weight of obese rats treated with high-fat diet plus ACT-335827 decreased significantly (P <0.05), while the abdominal and epididymis (P <0.05), but decreased the levels of serum lipids and fasting insulin (P <0.05). However, the levels of blood pressure, mesenteric fat There was no significant change in shoulder fat, HDL and NEFA (P <0.05). Conclusion: ACT-335827 can improve the metabolic disorder of obese rats and have some weight-loss effects on obese rats.