异氟烷对化疗性大鼠异食癖恶心呕吐模型神经功能及呕吐相关神经递质的影响

Effect of Isoflurane on Nerve Function and Vomiting-related Neurotransmitters in a Rat Model of Chemotherapeutic Pica Nausea and Vomiting

目的:研究异氟烷预处理对化疗性大鼠异食癖恶心呕吐模型神经功能及呕吐相关神经递质的影响。方法:选用SD大鼠作为研究对象,腹腔注射顺铂以建立化疗性大鼠异食癖恶心呕吐模型(Model组),腹腔注射等量生理研究作为对照组(Control),在腹腔注射顺铂前1 h和12 h吸入异氟烷预处理作为异氟烷治疗组(Isoflurane)。记录腹腔注射顺铂0~12 h和12~24 h内各组大鼠摄入高岭土量;在腹腔注射顺铂0 h、12 h和24 h后,通过神经功能缺损评分法对各组大鼠神经功能进行评分;并在腹腔注射顺铂24 h后处死大鼠,收集大鼠回肠和延髓组织以检测5-羟色胺(5-Hydroxytryptamine,5-HT)、5-羟基-吲哚乙酸(5-hydroxy-indole acetic acid,5-HIAA)、色氨酸羟化酶(Tryptophan hydroxylase,TPH)以及单胺氧化酶(Monoamine oxidase,MAOA)含量。结果:与Control组相比,Model组和Isoflurane组大鼠在腹腔注射顺铂0~12 h,12~24 h以及0~24 h内摄入的高岭土量均显著升高(P<0.05),并且Isoflurane组大鼠均显著Model组。三组大鼠在腹腔注射顺铂0 h、12 h和24 h后,神经功能评分均无显著差异(P>0.05)。与Control组大鼠相比,Model组和Isoflurane组大鼠在腹腔注射顺铂24 h后回肠/延髓组织内5-HT和TPH含量均显著升高,并且Isoflurane组大鼠显著低于Model组大鼠(P<0.05);与Control组相比,Model组大鼠回肠和延髓组织中5-HIAA/5-HIT比值和MAOA含量均显著降低(P<0.05);与Model组大鼠相比,Isoflurane组大鼠回肠5-HIAA含量、回肠/延髓5-HIAA/5-HT比值和MAOA含量均显著升高(P<0.05)。结论:异氟烷预处理可用于预防腹腔注射顺铂诱导的恶性呕吐,其机制可能与下降THP含量和提高MAOA含量,抑制5-HT合成以及促进5-HT代谢有关。

Objective: To study the effect of isoflurane pretreatment on the nerve function and vomiting-related neurotransmitters in a rat model of chemotherapeutic pica nausea and vomiting. Methods: SD rats were selected as the research object. Cisplatin was injected intraperitoneally to establish a chemotherapeutic rat pica nausea and vomiting model(Model group). The physiological study of intraperitoneal injection was used as the control group(Control). One was before the intraperitoneal injection of cisplatin. h and 12 h inhaled isoflurane pretreatment as isoflurane treatment group(Isoflurane). Record the amount of kaolin ingested by rats in each group within 0-12 h and 12-24 h of intraperitoneal injection of cisplatin;after intraperitoneal injection of cisplatin at 0, 12, and 24 hours, the rats in each group were evaluated by the neurological deficit score method. The neurological function was scored;and the rats were sacrificed24 hours after intraperitoneal injection of cisplatin. The rat ileum and medulla oblongata were collected to detect 5-hydroxytryptamine(5-Hydroxytryptamine, 5-HT), 5-hydroxy-indole acetic acid(5-Hydroxytryptamine, 5-HT). hydroxy-indole acetic acid(5-HIAA), tryptophan hydroxylase(TPH) and monoamine oxidase(MAOA) content. Results: Compared with the control group, the amount of kaolin ingested by rats in the model group and isoflurane group was significantly increased within 0~12 h, 12~24 h and 0~24 h after intraperitoneal injection of cisplatin(P<0.05). And the rats in the isoflurane group were significantly higher in the model group. After intraperitoneal injection of cisplatin at 0 h, 12 h and 24 h, the neurological function scores of the three groups of rats were not significantly different(P>0.05). Compared with the control group rats, the 5-HT and TPH levels in the ileum/medulla oblongata were significantly increased in the model group and isoflurane group rats after intraperitoneal injection of cisplatin for 24 hours, and the isoflurane group rats were significantly lower than those in the model group. Rats(P<0.05). Compared with the control group, the 5-HIAA/5-HIT ratio and MAOA content in the ileum and medulla oblongata of the model group were significantly reduced(P<0.05). Compared with the model group, The ileum 5-HIAA content, ileum/medullary bulb 5-HIAA/5-HT ratio and MAOA content of rats in the isoflurane group increased significantly(P<0.05). Conclusion: Isoflurane pretreatment can be used to prevent malignant vomiting induced by intraperitoneal injection of cisplatin. The mechanism may be related to the decrease of THP content and increase of MAOA content, inhibition of 5-HT synthesis and promotion of 5-HT metabolism.