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目的:观察食欲素(Orexin)和P物质(SP)对顺铂诱发大鼠异食癖的影响。方法:雄性Wistar大鼠被随机分为对照组和顺铂处理组,顺铂处理组给予大鼠顺铂(3或6 mg/kg,腹腔注射),对照组给予等量生理盐水。记录顺铂大鼠摄食高岭土量、摄食量的改变;Real-time PCR法观察顺铂对大鼠下丘脑Orexin和延髓中SP前体-前速激肽原A(PPT-A)m RNA表达的影响;分别和联合应用SP受体(NK1受体)拮抗剂阿瑞匹坦和Orexin-A对顺铂大鼠异食癖和摄食量的作用。结果:皮下注射3 mg/kg(低剂量组)的顺帕后大鼠高岭土摄入量和摄食量与对照组相比无明显差异(P>0.05),而注射6 mg/kg(高剂量组)顺铂后,大鼠高岭土摄入量与对照组和低剂量组相比显著增加(P<0.05);高剂量的顺铂作用12 h时,大鼠延髓内PPT-A的m RNA表达有轻微增加,但无统计学差异(P>0.05),24 h后,延髓内PPT-A的m RNA表达量显著增加(P<0.05)。在此后持续观察的5天中,顺铂可持续引起延髓中PPT-A的mRNA表达增高,在第5天时PPT-A的m RNA仍维持166.23±16.92%的高表达。高剂量顺铂抑制大鼠下丘脑中Orexin的mRNA表达,24 h时Orexin降低幅度最明显,为对照组的34.81±7.22%(P<0.05)。此后检测的5天,Orexin浓度均低于对照组;将阿瑞匹坦和orexin联合应用,大鼠高岭土摄入量较单独应用阿瑞匹坦或orexin明显减少,摄食量显著增加(P<0.05)。结论:P物质和orexin通路对顺铂化疗大鼠的异食癖和摄食量调控具有协同作用。
Objective: To observe the effects of orexin (Orexin) and substance P (SP) on cisplatin - induced pica. Methods: Male Wistar rats were randomly divided into control group and cisplatin treatment group, cisplatin (3 or 6 mg / kg, intraperitoneal injection) in cisplatin-treated group, and normal saline in control group. The contents of feeding kaolin and food intake of Cisplatin were recorded. Real-time PCR was used to observe the expression of PP precursor protein A (PPT-A) m RNA in the hypothalamus Orexin and medulla oblongata Effect; respectively and combined application of SP receptor (NK1 receptor) antagonist aprepitant and Orexin-A on cisplatin rat pica and the role of food intake. Results: There was no significant difference in intake and intake of kaolin after cisplatin 3 mg / kg (low dose) in rats injected subcutaneously (P> 0.05), while injection of 6 mg / kg ) Cisplatin significantly increased the amount of kaolin in rats compared with the control group and the low dose group (P <0.05). At 12 h of high dose cisplatin treatment, the m RNA expression in the medulla oblongata of rats (P> 0.05). After 24 h, the mRNA expression of PPT-A in medulla oblongata increased significantly (P <0.05). Cisplatin continued to induce PPT-A mRNA expression in the medulla oblongata for 5 consecutive days thereafter. On day 5, the m RNA of PPT-A remained highly expressed at 166.23 ± 16.92%. Orexin mRNA expression in the hypothalamus of rats was inhibited by high-dose cisplatin, and the decrease of Orexin was the most significant at 24 h, which was 34.81 ± 7.22% (P <0.05) of the control group. After 5 days of test, the Orexin concentration was lower than that of the control group. The combination of aprepitant and orexin significantly decreased the intake of kaolin in rats compared with aprepitant or orexin alone, and significantly increased the food intake (P <0.05 ). Conclusion: Substance P and orexin pathway have synergistic effect on the regulation of pica and food intake in cisplatin-treated rats.