止吐六味散对顺铂致异食癖模型大鼠5-HT和5-HT3A受体的影响

Effect of Zhitu Liuwei San on 5-HT and 5-HT3A in rats model induced by Cisplatin

目的以5-羟色胺（5-HT）为化疗诱发恶心呕吐的靶点，考察止吐六味散对顺铂致异食癖大鼠5-HT合成与代谢及5-HT3A受体表达的影响。方法将Wistar大鼠随机分为正常组、模型组、阳性药组（昂丹司琼）、给药组（止吐六味散低、中、高剂量），采用顺铂制备异食癖大鼠的模型。采用酶联免疫法测定大鼠血清、回肠、延髓中5-HT的含量，并测定回肠和延髓中色胺酸羟化酶（TPH）的水平和单胺氧化酶A（MAOA）的含量；采用Western blot法检测异食癖大鼠回肠和延髓中5-HT3A受体的表达。结果造模后72h，与正常组大鼠比较，各组大鼠血清、回肠和延髓中5-HT的含量均不同程度升高；药物治疗后，与模型组比较，昂丹司琼组与止吐六味散高、中、低剂量组大鼠血清、回肠、延髓中5-HT的含量均显著降低；与模型组比较，回肠中TPH1和延髓中TPH2的含量显著降低，回肠、延髓中的MAOA不同程度地显著升高。与模型组比较，各治疗组回肠和延髓中5-HT3A受体表达的水平均不同程度降低。结论止吐六味散对异食癖大鼠血清、回肠和延髓中5-HT的含量有明显的降低作用，对回肠和延髓中TPH的水平有下调作用以及MAOA的水平有上调作用；止吐六味散显著下调回肠和延髓中5-HT3A受体表达的水平，从而抑制了5-HT的合成，促进其代谢。其中，止吐六味散的中剂量与昂丹司琼的疗效相当。

OBJECTIVE To observe the effect of Zhitu Liuwei San（ZLS） on the synthesis and metabolism of 5 -hydroxytIyptamine （ 5 - HT） and the expression of 5 - HT3A receptor of rats pica induced by cisplatin. Taking 5 - HT as the target of nausea. METHODS According to the literature, the rat pica model was established. The Wistar rats were randomly divided into the normal group, model group, positive drug antiemetic group （Ondansetron） and ZLS group （low dose, middle dose and high dose ZLS groups）. The contents of 5 - HT in serum, ileum and medulla were determined by ELISA, and the levels of TPH and monoamine oxidase A （MAOA） in ileum and medulla oblongata were measured. The expression of 5 - HT3A receptor in ileum and medulla oblongata of pica rats were detected by Western blot method. RESULTS ELISA results showed that 72 h after modeling, the content of 5 - HT in serum and ileum and medulla of rats were increased, compared in different degrees with the normal group. After the drug treatment, compared with the model group, Ondansetron, ZLS high, medium and low dose group rats had decreased 5 - HT levels in serum and intestine. The level of 5 - HT in the medulla were significantly reduced with statistical significance. Compared with the model group ,the contents of TPH1 and TPH2 in the ileum decreased significantly, and the MAOA in the ileum and medulla oblongata increased significantly. The results of Western blot showed that compared with the model group, the expression levels of 5 - HT3A receptor in the ileum and medulla of each treatment group were significantly decreased in different degrees. CONCLUSION The contents of 5 - HT in serum,ileum and medulla oblongata of rats are significantly decreased. The level of TPH in ileum and medulla oblongata is down - regulated and the level of MAOA is up - regulated. The expression of 5 - HT3A receptor in ileum and medulla oblongata is significantly down - regulated by ZLS, which inhibits the synthesis of 5 - HT and promoted its metabolism.