【作者】 徐强；

【导师】 成大荣； 朱善元；

【作者基本信息】 扬州大学 ， 兽医硕士（专业学位）， 2022， 硕士

【摘要】 羊传染性胸膜肺炎是困扰肉羊养殖的最常见问题之一,是一种由绵羊肺炎支原体(Mycoplasma ovipneumoneia,Mo)、山羊支原体肺炎亚种(Mycoplasma capricolum subsp.capripneumoniae,Mccp)、丝状支原体山羊亚种(Mycoplasma capricolum subsp.mycodes,Mmc)或精氨酸支原体(Mycoplasma arginini,Ma)等引起的羊高度接触性呼吸道传染性疾病。该病在未接种过疫苗的养殖场,通常存在10%以上的发病率,消毒不力的养殖场可达20%以上;即使在已经接种过疫苗的养殖场,通常仍然存在5%左右的发病。80%以上的养殖场反应该病是影响肉羊生长、降低生产效应的重要因素。对该病的临床治疗通常是给发病肉羊注射相应药物;很多养殖场反应是治好了发病的,原来临床健康的又开始发病,呈现此起彼伏的态势。如何优化该病的给药方法,以保证发病肉羊的治疗效果和节约生产中人力成本,已经成为治疗的迫切需求。泰妙菌素是由担子菌侧耳属的高等真菌发酵得到的一种截短侧耳素类物质,在临床上泰妙菌素应用最广泛的形式是延胡索酸泰妙菌素。该药对支原体感染具有很好治疗效果,但在兽医药典中并没有其在肉羊上的应用指南。因此,本研究探索了延胡索酸泰妙菌素经雾化给药方式后在羊体内血浆的药物动力学和对羊传染性胸膜肺炎的治疗效果。在药动学研究中拟通过选取10只山羊随机分成雾化给药组和肌内注射对照组,每组5只,2组羊均按5 mg/kg延胡索酸泰妙菌素的剂量进行给药。在给药后第0 h、0.25 h、0.5 h、0.75 h、1 h、1.5 h、2h、4h、8h、12 h、24 h采集血浆,HPLC方法检测血浆药物浓度,并对两组羊的平均血浆药物浓度-时间进行药动学参数分析。结果显示5 mg/kg延胡索酸泰妙菌素经雾化给药方式和肌内注射给药方式对羊进行给药后在24 h内的平均血浆药物浓度的达峰浓度(Cmax)分别为0.50 μg/mL和0.58 μg/mL,达峰时间(Tmax)分别为雾化给药结束后0 h和肌内注射给药结束后0.25 h,消除半衰期(T1/2β)分别为1.40 h和3.40 h,药时下曲线面积(AUC0-∞)分别为0.66 h·μg/mL和2.27 h·μg/mL。在治疗效果研究中拟通过选择15只自然感染支原体的患羊,随机分成3组。第1组为雾化给药组,剂量为5 mg/kg,1 dl次,连续雾化3 d;第2组为肌内注射对照组,剂量为5 mg/kg,注射1次;第3组为不给药的空白对照组,分别于给药开始后0d、7 d、15 d采集3组患羊的鼻拭子样品,应用荧光定量PCR方法检测支原体感染强度,并在给药开始后0d、7d、15d、30d记录3组患羊的体重和临床症状变化情况。结果显示,在给药开始后7 d和15 d雾化给药组患羊的平均支原体感染强度相较于0 d分别下降了 78.27%和85.29%,有极显著统计学差异(P<0.001),且略优于肌内注射对照组的76.39%和80.60%,同时与空白对照组相比有极显著统计学差异(P<0.001)。雾化给药组患羊在给药开始后7 d、15 d、30 d相较于0d的平均体重增加率分别为5.64%、14.11%、31.87%,优于肌内注射对照组的5.20%、11.20%、25.44%,但均无统计学差异(P>0.05);同时也优于空白对照组的 5.00%、9.54%、21.86%,且在 15 d、30d 有统计学差异(0.01<P<0.05)。同时雾化给药组所有患羊在给药开始后7 d临床症状便全部消失,而肌内注射对照组在给药开始后15 d所有患羊临床症状全部消失,空白对照组患羊临床症状30 d内无好转。对有300只左右肉羊的羊舍进行雾化给药集成示范,结果显示,在集成示范之后原本有临床症状的肉羊临床症状均消失,同时原本临床健康的肉羊也未有出现临床症状的现象。药动学研究表明延胡索酸泰妙菌素经雾化给药方式相较于肌内注射给药方式血浆药物达峰浓度低更加安全,且消除更加迅速;比较3组羊的支原体感染强度变化、体重变化和临床症状变化情况的结果发现延胡索酸泰妙菌素经雾化给药方式对羊传染性胸膜肺炎的治疗效果要优于肌内注射给药方式;大批量给药时雾化给药方式相较于肌内注射给药方式更方便,且根据集成示范的结果,雾化给药方式对同群羊进行大批量给药后在治疗有临床症状肉羊的同时能对其它肉羊起到预防作用,能够做到对羊传染性胸膜肺炎的防治结合。综上所述,本研究认为延胡索酸泰妙菌素可应用雾化给药技术进行羊传染性胸膜肺炎的防控和治疗。更多还原

【Abstract】 Contagious pleuropneumonia of goat is one of the most common problems bothering food sheep and goat breeding.It is a highly contagious respiratory infectious disease caused by Mycoplasma ovipneumoniae,Mycoplasma capricolum subsp.capripneumoniae,Mycoplasma capricolum subsp.mycodes and Mycoplasma arginini etc,which can infect sheep and goat.The disease usually has an incidence rate of more than 10%in unvaccinated farms and more than 20%in poorly disinfected farms.Even in vaccinated farms,there is usually still about 5%of cases.More than 80%of the farms responded that the disease was a major factor affecting the growth of food sheep and goat and reducing the production effect.The clinical treatment of the disease is usually to inject corresponding drugs into the diseased food sheep and goat.Many farms responded that the disease food sheep and goat were cured,but the clinically healthy food sheep and goat began to get sick,showing a trend of one after another.How to optimize the drug administration of the disease to ensure the clinical cffects of the diseased food sheep and goat and save the labor cost in production has become an urgent need for treatment.Tiamulin,produced by basidiomycete pleurotus mutilus,is a kind of diterpene antibiotic pleuromutilin.Tiamulin fumarate is the most widely used form of tiamulin in clinic.It has a good clinical cffects on mycoplasma infection,but there is no guidelines in the Chinese Veterinary Pharmacopoeia for its use in food sheep and goat.Therefore,this study explored the pharmacokinetics of tiamulin fumarate in goat plasma and its clinical cffects on contagious pleuropneumonia of goat after atomization administration.In the study of pharmacokinetic,10 goats were randomly divided into atomization group and intramuscular injection group,with 5 goats in each group.The goats in both group were given 5 mg/kg tiamulin fumarate.Plasma samples were collected at 0 h,0.25 h,0.5 h,0.75 h,1 h,1.5 h,2 h,4 h,8 h,12 h and 24 h after administration.the plasma drug concentration was detected by HPLC,and the average plasma drug concentration-time of the two groups was analyzed.The results showed that the Cmax of the average plasma drug concentration within 24 hours after administration of 5 mg/kg tiamulin fumarate by atomization and intramuscular injection to goats were 0.50 μg/mL and 0.58 μg/mL,Tmax was 0 h after atomization administration and 0.25 h after intramuscular injection,and T1/2β was 1.40 h and 3.40 h,AUC0-∞was 0.66 h·μg/mL and 2.27 h·μg/mL.In the study of treatment effect,15 goats naturally infected with mycoplasma were randomly divided into 3 groups.The first group was the atomization administration group at the dose of 5 mg/kg,once per a day,for continuous 3 d.The second group was the intramuscular injection control group at the dose of 5 mg/kg once.The third group was blank control group without medication.The nasal swab samples of the goats in three groups were collected at 0 d,7 d,and 15 d after the start of administration,and the mycoplasma infection intensity of the three groups was detected by qPCR.The body weight and clinical symptom changes of the goats in three groups were recorded at 0 d,7 d,15 d and 30 d after the start of drug administration.The results showed that compared with 0 d,the average mycoplasma infection intensity of goats in the atomization administration group decreased by 78.27%and 85.29%at 7 d and 15 d after the start of administration,with extremely significant statistical difference(P<0.001).Those were slightly better than 76.39%and 80.60%in the intramuscular injection control group.At the same time,compared blank control group,those had a very significant difference(P<0.001).The mean body weight gains of the goats in the atomization administration group were 5.64%,14.11%,and 31.87%at 7 d,15 d,and 30 d.Thoes were better than 5.20%,11.20%,and 25.44%in the intramuscular injection control group,but those were no statistical difference(P>0.05).Meanwhile,those were better than 5.00%,9.54%and 21.86%in the blank control groups,and had statistically significant difference at 15 d and 30 d(0.01<P<0.05).At the same time,the clinical symptoms of all goats in the atomization group disappeared at 7 d,while the clinical symptoms of all goats in the intramuscular injection group disappeared at 15 d,and the clinical symptoms of the blank control group did not improve within 30 d.The integrated demonstration of atomization administration was carried out in the farm with about 300 food sheep and goat.The results showed that the clinical symptoms of the food sheep and goat with clinical symptoms disappeared after the integrated demonstration,and there were no clinical symptoms appeared in the originally clinically healthy food sheep and goat.The study of pharmacokinetic showed that the atomization administration of tiamulin fumarate was safer than intramuscular injection with low plasma peak concentration.By comparing the changes of mycoplasma infection intensity,body weight and clinical symptoms among the three groups,it was found that clinical effects of tiamulin fumarate on contagious pleuropneumonia of goat by using atomization administration better than intramuscular injection.Atomization administration is more convenient than intramuscular injection in mass administration,and according to the results of integrated demonstration,the method of atomization administration can prevent other food sheep and goat while treating food sheep and goat with clinical symptoms,and can achieve the combination of prevention and treatment of contagious pleuropneumonia of goat.In summary,this study holds that tiamulin fumarate can be used for the prevention and treatment of contagious pleuropneumonia of goat by using atomization administration technology.更多还原