侧脑室注射orexin对顺铂诱导大鼠异食癖的影响

Effects of Orexin on the Cisplatin-induced Pica in Rats

目的：研究化疗后止呕药联合侧脑室注射orexin能否改善顺铂诱导的异食癖与食欲减退,进一步探索吡嘧司特联合orexin抗呕吐的机制。方法：1腹腔注射止呕药并侧脑室置管给予orexin,观察大鼠高岭土摄取及摄食改变。2EIA法测量脑脊液中P物质含量。结果：1顺铂中高剂量组高岭土摄入增加、摄食和体重减少,呈量效依赖关系（P〈0.05~0.01）。2恩丹西酮早期抑制高岭土摄入（P〈0.05）。联合用药后延长该效应且晚期增加摄食（P〈0.05）。3阿瑞吡坦晚期抑制高岭土摄入,呈量效依赖关系（P〈0.05~0.01）,联合用药后第4天,高岭土摄取减少、摄食增加（P〈0.05）。4吡嘧司特晚期抑制高岭土摄入,呈量效依赖关系（P〈0.05~0.01）。高剂量吡嘧司特晚期增加摄食（P〈0.05）。联合用药后第4、5天,高岭土摄入减少,第1、4、5天摄食增加（P〈0.05）。5注射顺铂脑脊液中P物质浓度升高（P〈0.05）。联合用药能够降低P物质浓度（P〈0.05）。结论：联合应用orexin能够延长止呕药作用期并改善顺铂引起的食欲减退。吡嘧司特通过减少P物质的含量,抑制高岭土摄入。

Objective： To observe the effect of orexin on cisplatin induced pica in rat. Methods： Observe the changes of kaolin intake and feeding in rats by intraperitoneal injection of antiemetic drugs and lateral ventricle catheter with orexin; EIA was used to detect the substance P in cerebrospinal fluid. Results： ①In the high dose group, the kaolin intake, food intake and body weight were decreased, and there was a dose effect dependent relationship（P〈0.05-4）.01）. ②Ondansetron early suppression of kaolin intake （P〈0.05）. Combined use of drugs to prolong the effect and late increase in food intake （P〈0.05）. ③Aprepitant late inhibition of kaolin intake and dose-dependent relationship （P〈0.05-0.01）, 4 days after the drug combination, kaolin intake reduced, increased food intake （P〈0.05）.④ Pemirolast late inhibition of kaolin intake were dose-dependent （P〈0.05-0.01）. High dose ofpemirolast late increased feeding （P〈0.05）. After fourth and 5 days of combined administration, the intake of kaolin decreased, and the food intake increased in 1, 4 and 5 days （P〈0. 05）. OElevated substance P in CSF of injection ofcisplatin （P〈0.05）. Combined medication can reduce the substance concentration of P （P〈0.05）. Conclusion： The combined application of orexin can prolong the period and improve the effect of antiemetic drugs cisplatin induced anorexia. Pemirolast by reducing the content of substance P, inhibition of kaolin intake.