| Objective:To observe the effect of substance SP and orexin on cisplatin induced pica in rat.Methods: Male Wistar rats were randomly divided into control group and cisplatin treatment group.The rats in the treatment group were treated with intraperitoneal injection of cisplatin(3 or 6 mg/kg),and the control group was given equal volume of normal saline.To observe the effect of rat kaolin consumptions and food intake changes;the expression of orexin in hypothalamus ARC by immunofluorescence histochemistry;Realtime PCR assay of cisplatin on orexin in hypothalamus and medulla of rats in SP precursor-preprotachykinin A(PPT-A)m RNA expression respectively;and combined application of SP receptor(NK1 receptor)antagonist aprepitant and orexin-A,observe its effect on cisplatin induced pica in rats and food intake.Results:Intraperitoneal injection of 3 mg/kg(low dose group)CIS PA,kaolin intake and food intake of rats compared with the control group had no significant difference(P > 0.05),and the injection of 6 mg/kg(high dose group)after cisplatin in rats,the kaolin intake compared with control group and low dose group increased significantly(P < 0.05);injection of high dose cisplatin 12 h,PPT-A m RNA expression in medulla of rats was increased slightly,but compared with the control group had no statistical significance(P > 0.05);but the injection of high dose cisplatin 24 h,PPT-A in medulla of m RNA expression was significantly increased(P < 0.05).During the 5 days of continuous observation,m RNA PPT-A expression was significantly higher(P < 0.05),and m RNA PPT-A remained at a relatively high level in fifth days(P < 0.05).Intraperitoneal injection of high dose of cisplatin significantly inhibited the expression of m RNA Orexin in hypothalamus of rats,the most significant reduction of Orexin in 24 h injection was 34.81 + 7.22%(P < 0.05)in control group.5 day after the injection,the concentration of Orexin was lower than the control group(P < 0.05);intraperitoneal injection of aprepitant in rats,kaolin intake significantly reduced(P < 0.05),but no significant change in food intake(P > 0.05);microinjection of Orexin-A into the lateral ventricle of rats significantly decreased(P kaolin intake < 0.05),and food intake increased significantly(P < 0.05);combined application of aprepitant and Orexin-A to cisplatin pica in rats and the effect of reduced food intake was significantly lower(P < 0.05),significantly better than pure aprepitant or Orexin-A(P < 0.05).Suggests that the P and Orexin signaling pathway may have synergistic effects on the regulation of the different eating habit and food intake in rats with cisplatin chemotherapy.Conclusions: Aprepitant and orexin can reduce kaolin intake and increase food intake in rats induced by cisplatin chemotherapy,the effect may be related to the activation of P and Orexin signaling pathway. |
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