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畜禽疫苗免疫应激及其抗应激剂研究

Study on Immunological Stress during Vaccination and Preparetion and Application of Anti-stress Agent in Domestic Animals and Fowls

【作者】 文利新

【导师】 袁慧;

【作者基本信息】 湖南农业大学 , 临床兽医学, 2009, 博士

【摘要】 本研究针对畜禽疫苗免疫应激这一生产难题,以猪和鸡为实验动物,开展了猪瘟疫苗、口蹄疫疫苗、蓝耳病疫苗和鸡新城疫Ⅱ系苗的免疫应激机理及其调控研究、抗应激剂研制。结果表明:①口蹄疫疫苗、蓝耳病灭活疫苗、猪瘟疫苗和鸡新城疫Ⅱ系疫苗均能引起机体的“疫苗免疫应激”;②通过雏鸡模型研究发现,疫苗免疫应激机理之一是从基因水平调控下丘脑内的CRH mRNA和TRH mRNA的显著表达从而调控ACTH和糖皮质激素-皮质醇分泌而引起应激;③研究发现虾青素对鸡新城疫Ⅱ系苗免疫应激具有抗应激和免疫调控作用,其能够从基因水平调控CRH mRNA和TRH mRNA的表达,减少CRH和TRH的分泌,从而减少免疫应激反应,显著提高肉鸡日增重;④研究发现谷氨酰胺对鸡新城疫Ⅱ系苗免疫应激具有抗应激和免疫调控作用,其能从基因水平调控下丘脑中的CRHmRNA和TRH mRNA表达水平,极显著减少其分泌,显著提高肉鸡日增重、血清抗体水平和溶菌酶的含量,极显著提高脾脏和胸腺的脏器指数;⑤研制了抗免疫应激剂“促免1号”,具有缓解猪和鸡的免疫应激,提高日增重、成活率和饲料转化率以及提高抗体水平的作用;研制了口蹄疫抗免疫应激剂ASFP-1,其能预防口蹄疫疫苗引起的过敏和体温升高,显著提高猪的日增重和降低料肉比,显著降低血清ACTH和皮质醇水平,同时,抗体水平不受影响;研制了蓝耳病疫苗的免疫增强调节剂,能缓解蓝耳病疫苗引起的免疫应激的症状,显著提高仔猪的蓝耳病IgG抗体水平,抗体生成时间提前10d。结论:本研究证实了畜禽疫苗是一种特殊应激原,能导致机体的“疫苗免疫应激”,其机理之一是从基因水平调控下丘脑内的CRH mRNA和TRH mRNA的显著表达;研究发现虾青素和谷氨酰胺具有抗免疫应激和免疫调节作用;成功研制了抗免疫应激剂“促免1号”,口蹄疫抗免疫应激剂ASFP-1,蓝耳病疫苗的免疫增强调节剂IRFF等3个新产品,申请发明专利2项。

【Abstract】 To cope with immunological stress during vaccination in production of animals and fowls in pig and chicken were used as experimental models, mechanism and regulation for immunological stress of swine fever (SF) , foot and mouth disease, porcine reproductive and respiratory syndrome (PRRS) , Newcastle disease (ND) vaccination were studied, and their anti-stress agents were prepared respectively. The results were as follows.1) Vaccination by using Foot and mouth disease vaccine, porcine reproductive and respiratory syndrome vaccine, swine fever vaccine and Newcastle disease vaccine II could cause immunological stress in animals and fowls production.2) Based on the study of chicken model, it was shown that one of mechanisms for immunological stress induced by vaccination was regulatory effect of Corticotropin-releasing hormone (CRH) and Thyrotropin-releasing hormone (TRH) gene expression. The study confirmed that CRH mRNA and TRH mRNA in hypothalamus were significantly expressed, and regulated secretion of adrenocorticotropic hormone (ACTH) and cortisol, which finally led to immunological stress.3) Astaxanthin had effect of anti-stress and immunological regulation during vaccination of Newcastle disease vaccine II, it could cause the decrease of secretion of CRH and TRH by regulating gene expression of CRH mRNA and TRH mRNA, which finally led to the decrease of immunological stress response. Moreover, it could cause the increase of daily gain for broilers.4) Glutamine played an important role in anti-stress and immunological regulation during vaccination of Newcastle disease vaccine II, it could cause the significant decrease of secretion of CRH and TRH by regulating expression of CRH mRNA and TRH mRNA in hypothalamus, moreover, daily gain of broilers, antibody titer and concentration of lysozyme in sera were significantly increased, organ index of spleen and thymic were very significantly increased.5) Anti-immunological stress agents "Cumian No.1" was prepared, it could alleviate immunological stress of pig and chicken, increase daily gain, survival rate, feed conversion ratio (FCR) and antibody titer of pig and chicken. Anti-immunological stress agents ASFP-1 for foot and mouth disease vaccination was prepared, it could prevent allergy and fervescence, significantly increase daily gain and decrease feed conversion ratio of pig. It could significantly decrease concentration of ACTH and cortisol in sera, meanwhile not affect antibody titer in sera. Immunoenhancement regulator of PRRS vaccination was also prepared, it could alleviate symptoms of immunological stress caused by PRRS vaccination, IgG concentration in sera was significantly increased by injecting Immunoenhancement regulator agents IRFF of PRRS, formation of neutralizing antibody is 10 days aheadThe research confirmed that inoculation vaccine for ainmals and fowls were special stress sources, one of it’s mechanisms could be significant regulatory effect of CRH and TRH mRNA expression in hypothalamus. The results showed Astaxanthin and Glutamine played important roles in anti-immunological stress and immune regulation. The products for Anti-immunological stress agents "Cumian No.1", anti-immunological stress agents ASFP-1 of foot and mouth disease vaccination and immunoenhancement regulator of PRRS vaccination were successfully prepared, 2 invention patents have been successfully obtained

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