牛羊腹泻口服液对靶动物牦牛的安全性试验

Safety test of cattle-sheep oral liquid for diarrhea on target animal yaks

为了评价牛羊腹泻口服液在建议剂量下对靶动物牦牛的安全性,试验将20头待宰牦牛分为4组,分别为对照组及1,3,5倍剂量组,每组5头,对照组灌服生理盐水,1,3,5倍剂量组分别以建议剂量的1,3,5倍剂量进行连续15 d口服给药。试验期间每天给药前后观察并记录牦牛的精神、采食、饮水及二便等临床体征;并在给药后第0,5,10,15天分别采集血液,检测血常规和血清生化指标;最后一次采血后将牦牛屠宰并解剖,采集肝脏、肾脏组织制作病理切片,H.E.染色后观察肝脏、肾脏组织的病理变化。结果表明:不同剂量连续给药15 d对受试牦牛的临床体征无明显影响。在第0天时,对照组的嗜酸性粒细胞数(EO)显著高于1,3倍剂量组(P<0.05),而中性粒细胞(NEUT)比率显著低于1,3,5倍剂量组(P<0.05);在第5天时,3倍剂量组的平均红细胞体积(MCV)显著高于对照组(P<0.05),而对照组的NEUT比率显著低于1,3,5倍剂量组(P<0.05);在第10天时,对照组的MCV显著高于1,3,5倍剂量组(P<0.05),平均红细胞血红蛋白含量(MCH)显著高于1,5倍剂量组(P<0.05),而平均红细胞血红蛋白浓度(MCHC)显著低于1,3,5倍剂量组(P<0.05);在第15天时,对照组的MCV、血细胞比容(HCT)均显著高于1,3,5倍剂量组(P<0.05),MCH显著高于1,5倍剂量组(P<0.05),大型血小板比率(P-LCR)显著高于5倍剂量组(P<0.05),MCHC显著低于1,3,5倍剂量组(P<0.05),NEUT比率显著低于1,3倍剂量组(P<0.05),各组间其他指标均差异不显著(P>0.05)。在第0天时,3倍剂量组的碱性磷酸酶(ALP)活性显著低于5倍剂量组(P<0.05);在第5天时,对照组的总蛋白(TP)含量显著低于3,5倍剂量组(P<0.05);在第15天时,对照组的白蛋白(ALB)含量显著高于1,3倍剂量组(P<0.05),各组间其他指标均差异不显著(P>0.05)。H.E.染色结果发现,各组牦牛肝脏、肾脏组织结构除偶见出血外大致正常。说明牛羊腹泻口服液在1倍建议剂量下使用对靶动物牦牛具有安全性。

In order to evaluate the safety of cattle-sheep oral liquid for diarrhea at the recommended dose to target animal yaks, in the experiment, 20 yaks to be slaughtered were divided into 4 groups(control group and 1,3,5 times dose groups), with 5 heads in each group.The control group was given normal saline, and 1,3,5 times dose groups were administered orally at 0, 1, 3, and 5 times the recommended dose for 15 consecutive days. During the test period, the clinical signs such as the yak’s spirit, food intake, drinking water, urine and stool were observed and recorded before and after administration every day;and on the 0 th, 5 th, 10 th and 15 th days after administration, blood was collected, and blood routine and serum biochemical indexes were detected. After the last blood collection, the yaks were slaughtered and dissected, and the liver and kidney tissues were collected to make pathological sections;after H.E. staining, the pathological changes of the liver and kidney tissues were observed. The results showed that continuous administration of different doses for 15 days had no significant effect on the clinical signs of the tested yaks. On day 0, the number of eosinophils(EO) in the control group was significantly higher than that in the 1, 3 times dose group(P<0.05), while the percentage of neutrophils(NEUT) was significantly lower than that in the 1, 3 and 5 times dose group(P<0.05).On the 5 th day, the mean corpuscular volume(MCV) of the 3 times dose group was significantly higher than that of the control group(P<0.05), while the percentage of NEUT in the control group was significantly lower than that of the 1, 3 and 5 times dose groups(P<0.05). On the 10 th day, the MCV of the control group was significantly higher than that of the 1, 3 and 5 times dose groups(P<0.05), and the mean corpuscular hemoglobin(MCH) was significantly higher than that of the 1, 5 times dose group(P<0.05);the mean corpuscular hemoglobin concentration(MCHC) was significantly lower than 1, 3 and 5 times dose group(P<0.05). On the 15 th day, the MCV and hematocrit(HCT) of the control group were significantly higher than those of the 1, 3 and 5 times dose groups(P<0.05), and the MCH was significantly higher than those of the 1, 5 times dose group(P<0.05);the platelet-larger cell ratio(P-LCR) was significantly higher than that in the 5 times dose group(P<0.05), the MCHC was significantly lower than that in the 1, 3 and 5 times dose groups(P<0.05), and the percentage of NEUT was significantly lower than that in the 1, 3 times dose group(P<0.05);other indicators were not significantly different among the groups(P>0.05). On the 0 th day, the alkaline phosphatase(ALP) activity of the 3 times dose group was significantly lower than that of the 5 times dose group(P<0.05). On the 5 th day, the total protein(TP) content of the control group was significantly lower than the 3, 5 times dose group(P<0.05). On the 15 th day, the albumin(ALB) content of the control group was significantly higher than that of the 1 and 3 times dose groups(P<0.05), and there was no significant difference in other indicators between the groups(P>0.05). The results of H.E. staining showed that the structures of the liver and kidney tissues of yaks in each group were generally normal except for occasional hemorrhage. The results suggested that the cattle-sheep oral liquid for diarrhea was safe for the target animal yaks when used at the recommended dose.