【作者】 哈斯苏荣；

【导师】 蒋金书；

【作者基本信息】 中国农业大学 ， 预防兽医学， 2004， 博士

【摘要】 复方丁氨丙磷是由有机磷化合物和维生素组成的一种能量代谢促进剂、免疫增强剂和抗应激药。可用于由营养不良、饲养管理不合理或疾病引起的动物代谢紊乱、母畜产后疾病和不孕症以及幼畜发育不良、免疫功能低下和各种应激反应等的防治，还可当作能量补充剂和强壮剂用于过度使役或疲惫的动物。本课题组经过多年的研究自行合成了复方丁氨丙磷的主要有效成分—丁氨丙磷，并研制出两种类似制剂，分别命名为复方丁氨丙磷溶液和复方丁氨丙磷注射液。本文主要对复方丁氨丙磷溶液的药效学进行研究。 复方丁氨丙磷溶液对肉雏生产性能和血液生理生化指标的影响 将1日龄肉雏，随机分成4组。于7日龄开始分别滴服0.50mL生理盐水和0.25mL、0.50mL和0.75mL的复方丁氨丙磷溶液，检测各组肉雏的增重、采食量、血红蛋白含量和血清生化指标。试验结果表明，各组肉雏终末体重间未见显著差异，但给药组肉雏的体重和饲料转化率有明显增加的趋势；在试验初期，给予中剂量和高剂量给药组肉雏血红蛋白含量显著低于对照组和低剂量给药组，但在试验后期低剂量给药组的血红蛋白含量显著高出其余3组(p＜0.05)；各组肉雏的血清无机磷、总蛋白和清蛋白含量未见有明显规律性变化；在试验初期，血清碱性磷酸酶、谷草转氨酶和谷丙转氨酶含量随给药剂量呈下降趋势；各给药组肉雏血清肌酸磷酸激酶含量在整个试验期均明显下降，血糖含量略有增加，血清球蛋白含量明显增加(p＜0.05)。 复方丁氨丙磷溶液对机体能量代谢的影响 将24只小鼠，随机分成对照组和给药组，前者按10mL／kg灌胃给予生理盐水；后者按250mg／kg灌胃给予复方丁氨丙磷溶液。采用经典蒽酮显色法和反相高效液相色谱法分别测定各组小鼠肝脏和骨骼肌中的糖原含量和3种磷酸腺苷含量，并借助电子显微镜观察肝细胞和肌细胞线粒体的数量和形态特征。试验结果表明，复方丁氨丙磷溶液能显著升高小鼠肝糖原和肌糖原含量以及肝组织和肌肉组织的三磷酸腺苷(ATP)、二磷酸腺苷(ADP)的含量，对肝组织一磷酸腺苷(AMP)的含量未见明显影响，却使肌肉组织AMP的含量有一定程度的下降。本品还能明显增加肝细胞和肌细胞的线粒体数量和体积。上述试验结果表明，复方丁氨丙磷溶液是通过增加肝糖原和肌糖原储备、促进ATP和ADP的合成以及影响线粒体超微结构和数量来加强动物机体的能量代谢。 复方丁氨丙磷溶液的免疫增强作用 将48只小鼠随机分成4组，即阴性对照组，按10mL／kg内服生理盐水；阳性对照组，按100mg／kg内服左旋咪唑；低剂量给药组，按125mg／kg内服复方丁氨丙磷溶液；高剂量给药组，按250mg/kg内服复方丁氨丙磷溶液。采用碳廓清法、流式细胞术和分光光度法分别检测各组小鼠单核—巨噬细胞吞噬功能、外周血淋巴细胞CD4~+、CD8~+和CD19~+细胞百分含量以及血清溶血素。试验结果表明，高剂量给药组小鼠吞噬指数显著(p＜0.05)高于阴性对照组；各给药组小鼠外周血淋巴细胞CD4~+细胞百分率和CD4~+／CD8~+值均明显(p＜0.05)高于阴性对照组，且血清溶血素含量均极显著地(p＜0.001)高于阴性对照组和阳性对照组。因此，本品是通过增强机体非特异性防御机能和特异性细胞免疫反应以及特异性体液免疫功能来增强机体的免疫功能。 复方丁氨丙磷溶液的抗应激作用 通过小鼠耐寒、耐热、耐缺氧和负荷游泳实验，研究复中国农业大学博士学位论文中文摘要旦里里里口巴里里里口口里里里里里里里旦口目里旦旦目口里旦组典典里口旦组组里目组里方丁氨丙磷溶液对小鼠急性应激反应的影响。将小鼠分成对照组和两个剂量级给药组共3组，分别给予生理盐水和按125m叭g、250m叭g给予复方丁氨丙磷溶液。试验结果表明，本品能明显提高小鼠耐寒、耐热和耐缺氧能力，并能明显延长小鼠负荷游泳时间。为进一步研究本品对动物慢性冷应激和热应激反应的影响，将试验肉雏分成对照组和两个剂量级给药组，分别给予生理盐水和按0.lmL/只、0.3mL/只滴服复方丁氨丙磷溶液。分别检测各组肉雏生产性能、体温、以及血清乃、T4、胰岛素和皮质醇等部分内分泌激素，血清肌酸磷酸激酶、碱性磷酸酶、乳酸脱氢酶和血糖等生化指标。试验结果表明，本品对由热或冷应激导致的肉雏生产性能的下降有一定的改善作用，能显著降低冷应激和热应激肉雏的血清肌酸磷酸激酶和碱性磷酸酶含量，并使血糖含量上升;能显著升高热应激肉雏毛瓜值和胰岛素含量，而对血清皮质醇含量未见显著影响。此外，还能升高冷应激肉雏血清毛和T;含量，降低血清皮质醇含量，但对血清乳酸脱氢酶活性、胰岛素含量和T3厅;值无显著影响。 复方丁氨丙磷溶液对球虫病的辅助治疗作用根据试验肉雏生产性能、临床发病症状、盲肠病变、卵囊值和抗球虫指数等各项指标，综合评价复方丁氨丙磷溶液对肉雏柔嫩艾美耳球虫病的辅助治疗作用。试验结果表明，复方丁氨丙磷溶液能较明显地改善感染肉雏的日增重和饲料转化率，各给药组肉雏的抗球虫指数在123.3一138.3之间，根据评价标准属于低效抗球虫药，不能单独用作抗球虫药物，但对肉雏球虫病的防治上确有一定的辅助治疗作用。更多还原

【Abstract】 Compound butafosfan is a metabolic stimulant, immune potentiator and anti-stress organic agent. It was used mainly for animal metabolic disorders caused by malnutrition or faulty husbandry; developmental and nutrional disorders in young animals resulting from diseases during the growing period; metaphylaxis of sterility and puerperal diseases and also as supportive treatment for sterility, parasitic infeststion or bacterial desease; and as an effective tonic and energy metabolic stimulant in cases of over-exertion and exhaustion. The main component of compound butafosfan has been synthesized successfully, and two similar preparations, named compound butafosfan solution and compound butafosfan injection, have been developed and studied separately. We have studied on pharmacodynamics of compound butafosfan solution in this research.Effects of compound butafosfan solution on performance and blood physiological and biochemical parameters in broilers: One-day old broilers were selected and divided into 4 groups at random, and physiological saline (control) and different doses (0.25ml, 0.5ml and 0.75ml/each) of compound butafosfan solution (experimental) were respectively dipped orally to 7-day old broilers in 5 successive days. Average daily gain, daily feed intake, gain/feed, hemoglobin and biochemical parameters were determined. The experimental results showed that there were no statistically differences between weights of among all groups, but the average daily gain and gain/feed in the experimental groups had shown the potential increasing. The hemoglobin content in groups of 0.5ml/each and 0.75ml/each was obviously lower than that in group 0.25ml/each and control at the very beginning of the test, however, the hemoglobin content in group of 0.25ml/each was significantly increased to higher than other experimental groups and control groups at the end of the test. The serum contents of ALP, I PHOS, PT, ALB, GOT and GPT in all experimental groups have not appeared regular changes. The contents of CK in all experimental groups were decreased with the increasing of dose. Moreover, serum GLU content was slightly higher than control group. Serum globulin content in experimental groups was significantly higher than that in control group.Effects of compound butafosfan solution on animal energy metabolism: The mice were assigned to 2 groups of control and experimental, and were dipped orally to physiological saline and 250mg/kg of compound respectively. The contents of liver glycogen and skeletal muscle glycogen were determined by classical anthrone colourimetry and the contents of 3 kinds adenosine phosphates were detected by HPLC, respectively, and the quantity and morphology of mitochondria in both liver and muscle cells was observed by electron microscope, simultaneously. The experimental results showed that the content of glycogen, also ATP and ADP in both liver and muscle tissue from experimental groups were significantly increased, however, the AMP content in liver was not affected by butafosfan and that in muscle was decreased. The quantity, distribution and microstructure of mitochondria in both liver and muscle cells were also affected by compound butafosfan solution.These experimental results indicated that compound butafosfan solution could significantly enhanced the energy metabolism in mice by increasing the glycogen storage both in liver and muscle cells and promoting the synthesis of ATP and ADP, and influencing the quantity and microstructure of mitochondria in both kinds of cells.Immune stimulating properties of compound butafosfan solution: The mice were devided into 4 groups with control, group of levamisole, groups of 125mg/kg and 250mg/kg of butafosfan compound solution. The phagocytosis of mononuclear phagocyte system, percentage of CD4+, CD8+ and CD19+ lymphocytes in peripheral blood and anti-sheep blood cell hemolysin were determined by using carbon particle clearance test, flow cytometry and spectrophotometry, respectively. The experimental results showed that the compound butaf更多还原