【作者】 刘磊；

【导师】 李引乾；

【作者基本信息】 西北农林科技大学 ， 基础兽医学， 2010， 硕士

【摘要】 戈那瑞林为人工合成的GnRH类似物,肌注之后,它通过提高普通的下丘脑-垂体功能,改善总体受精率,从而恢复卵泡的正常生长和成熟。本试验拟研究戈那瑞林在奶牛体内药物代谢动力学、奶牛卵巢囊肿的治疗效果以及其对奶牛生理生化指标的影响,为该药的进一步推广应用提供临床资料。结果如下:1.戈那瑞林在奶牛体内的药动学研究戈那瑞林(Gonadorelin)为人工合成的促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)类似物。为了分析戈那瑞林在奶牛体内的药物代谢动力学过程,为兽医临床合理用药提供理论依据,对6头奶牛进行摘除卵巢手术,术后30 d单剂量肌内注射用戈那瑞林,16 h内不同时间19次静脉采血,应用酶联免疫吸附法(ELISA)测定血清中促性腺激素释放激素(GnRH)浓度,残数法拟合药时曲线,计算药物动力学参数。结果显示,戈那瑞林在奶牛体内的药物动力学配置符合有吸收因素二室开放模型,其药—时曲线最佳方程为C=68.7632e-7.6743t+9.6987e-0.4437t-78.4619e-16.0215t。主要药物动力学参数:消除相半衰期t1/2β为1.5638±0.0661 h,药-时曲线下面积AUC为25.6411±2.3926 ng·mL-1·h,达峰浓度为24.2902±3.6515 ng·mL-1,达峰时间为0.1033±0.0150 h。结果表明,奶牛肌注戈那瑞林后,吸收快,消除也快。2.戈那瑞林对奶牛卵泡囊肿的临床治疗试验为了了解戈那瑞林对奶牛卵泡囊肿的治疗效果。利用临床检查、直肠检查和B超诊断仪综合诊断出的40头患卵泡囊肿的奶牛并分为戈那瑞林治疗组和药物对照(黄体酮)治疗组。戈那瑞林组分为高、中(推荐剂量)、低三个试验组,每组试验动物10头,高、中(推荐剂量)、低3个试验组分别于第1天,第2天和第9天各肌注“注射用戈那瑞林”200μg、100μg和50μg,黄体酮对照组,奶牛每次50 mg~150 mg,每天或隔天肌注一次,连用2~7 d。以临床症状是否消失,B超探查患卵泡囊肿的卵巢体积是否恢复至正常以及奶牛是否能恢复正常发情周期并发情配种,判定戈那瑞林对奶牛卵泡囊肿的治疗效果。结果显示,经戈那瑞林治疗后,患卵巢囊肿奶牛临床症状消失或明显改善,B超探查,患卵泡囊肿的卵巢体积恢复至正常,大部分奶牛恢复正常发情周期并发情配种。结果说明,于第一天、第二天和第9天给牛肌肉注射戈那瑞林100μg,可有效治疗奶牛卵泡囊肿。3.戈那瑞林对奶牛生理生化指标的影响的研究为了了解戈那瑞林对奶牛生理生化指标的影响,给奶牛单剂量注射戈那瑞林100μg后测定奶牛生理生化指标。结果显示,奶牛注射戈那瑞林后,对奶牛体温、呼吸频率、心率及血液学指标进行测定,均未发现异常。结果说明戈那瑞林对于奶牛的生理生化指标没有影响。更多还原

【Abstract】 Gonadorelin, a synthetic GnRH analogue, can raise the normal hypothalamus-pituitary function and improve the overall fertility rate to recover thereby the normal growth and maturation of follicular after intramuscular injection. In order to provide clinical information for the further application of Gonadorelin, the "Gonadorelin" pharmacokinetics in cows, its treatment dairy ovarian cysts, physiological and biochemical indices of blood in cows , were researched in this study. The detail is as follows:1. Study on pharmacokinetics of Gonadorelin in cows Gonadorelin is a synthetic GnRH analogues. In order to analyze the pharmacokinetic course of Gonadorelin in cows and provid theoretical basis of rational drug using for clinical veterinary surgeon, six cows were excised ovaries and injected Gonadorelin by single-dose 30 days after the operation.Then blood was collected 19 times in different time of 16 hours after intramuscular injection. The concentration of GnRH in serum was determined by ELISA, and the concentration-time curve and the pharmacokinetic parameters were made by residual method. The results show that the pharmacokinetics allocation of Gonadorelin in cows is in line with the two-compartment open model with the coefficient of absorption.The best medicine-time curve equation is C=68.7632e-7.6743t+9.6987e-0.4437t-78.4619e-16.0215t .The main pharmacokinetic parameters : The half - time of beta phase of it (t1/2β) is 1.5638±0.0661 h, the area under curve (AUC) is 25.6411±2.3926 ng·mL-1·h, the peak concentration is 24.2902±3.6515 ng·mL-1 , the time to peak is 0.1033±0.0150 h. The results show that it absorbs quickly and eliminates quickly too after intramuscular injection of Gonadorelin in cows.2. Treament of Gonadorelin to dairy ovarian cysts In order to understand the Treament of Gonadorelin to dairy ovarian cysts, according to the comprehensive diagnosis including the clinical examination, rectal examination and examination by B-type ultrasonic diagnostic apparatus, the 40 cows suffered from cystic graafian follicles are divided into Gonadorelin the treatment group and drug control (progesterone) group. Gonadorelin group was divided into three test groups of 10 cows in each group which consist of high dose group, medium dose group (the recommended dose) and low dose group. The three test groups were injected with Gonadorelin for Injection 200μg , 100μg and 50μg on first, second and nineth day. Progesterone control group is injected with progesterone 50 mg~150 mg per cow every day or the next day lasting of 2~7 days. Based on the disappearance of clinical symptoms, ovary back to normal size by B-type ultrasonic diagnostic apparatus as well as the cows returning to normal estrus cycle, the therapeutic effect on cystic graafian follicle in cows by Gonadorelin was determined. The results show that after being treated with Gonadorelin, the clinical symptoms of ovarian cysts in cows were disappeared or markedly improved, ovary is back to normal size, the majority of cows return to normal estrus cycle and estrus service. The results showed that injected gonadorelin 100μg to cows in the first day, second day and 9th day, the cows ovarian cysts can be effectively treated.3. Effects of Gonadorelin on physiological and biochemical indices of blood in cowsIn order to understand the effects of Gonadorelin on physiological and biochemical indices of blood in cows,detected the physiological and biochemical indices of blood after injecting a single dose of 100μg gonadorelin to cows. The results showed that the indicators about cows including temperature, respiration rate, heart rate and blood parameters were all normal afer injecting the cows with Gonadorelin.The results showed that there were no effect to the dariy cows on physiological and biochemical indices of blood.更多还原