影响急进4010m高原大鼠药代动力学参数的诸因素变化

目的:观察平原Wistar大鼠急进高原后以及急进高原返回平原后,影响其药物代谢动力学参数的诸因素变化。方法:将21只Wistar大鼠随机均分为3组,分别在平原地区(上海55 m)、急进高原(甘肃玛曲4010 m)和急进高原返回平原后,于大鼠眼眶采血分析其主要生化指标,腹主动脉采血进行血气分析,完整摘取脑、肺、肾后进行病理改变的研究。结果:急进高原组与平原组比较pH值、缓冲碱、碱剩余、总二氧化碳含量、动脉血氧饱和度、动脉血氧分压、血清钠离子浓度、乳酸脱氢酶以及总蛋白显著降低(均P<0.05),动脉血二氧化碳分压、血清氯离子浓度、总胆红素以及碱性磷酸酶显著升高(均P<0.05);急进高原返回平原组与平原组相比较pH值、缓冲碱、碱剩余、动脉血氧饱和度、动脉血氧分压、血红蛋白、血清钠离子浓度、乳酸脱氢酶以及总蛋白显著降低,动脉血二氧化碳分压、血清氯离子浓度、丙氨酸氨基转移酶、总胆红素以及尿素显著升高(均P<0.05);急进高原返回平原组与急进高原组比较血红蛋白与碱性磷酸酶显著降低(均P<0.05),总蛋白、总胆红素及尿素显著升高(均P<0.05)。病理结果可见急进高原组与急进高原返回平原组均有不同程度的肺泡壁增厚、充血、水肿,肺泡上皮增生,肺泡间隔增宽,中性粒细胞浸润;大脑神经元细胞水肿并血管周围间隙形成,海马神经元变性,核固缩;肾小球系膜细胞增生。结论:急进高原与急进高原返回平原组大鼠血气指标、生化指标以及心、肝、肾功能均发生明显改变,脑、肺、肾均可见明显病理改变,严重影响药物的药代动力学参数。

Changes in factors affecting pharmacokinetics in Wistar rats after acute exposure to high altitude of 4010 meters

Objective: To observe changes in factors affecting pharmacokinetics in rats after acute exposure to high altitude and their reacclimation to low altitude.Methods: Twenty-one male Wistar rats were randomly assigned into 3 groups: Group A(plain area,at Shanghai,55 m above sea level),Group B(acute exposure to high altitude,Maqu,Gansu,4010 m above sea level),and Group C(acute exposure to high altitude and then back to the plain area).Blood was collected from orbit to analyze the main biochemical indicators;blood was collected from the abdominal aorta for blood gas analysis;and tissues— brain,lung,and kidney — were totally removed to observe pathological changes.Results: Compared with Group A,in Group B the pH,buffer base,base excess,total carbon dioxide level,oxgyen saturation of arterial blood,oxygen tension of arterial blood,serum sodium,serum lactate dehydrogenase,and total serum protein were all significantly reduced,while carbon dioxide tension of arterial blood,serum chlorine,and serum alkaline phosphatase were all significantly increased(P<0.05).In Group C,the pH,buffer base,base excess,oxgyen saturation of arterial blood,oxygen tension of arterial blood,hemoglobin,serum sodium,serum lactate dehydrogenase,and total serum protein were significantly reduced,while carbon dioxide tension of arterial blood,serum chlorine,serum alanine transarninase,total bilirubin and urea were significantly increased(P<0.05).The hemoglobin and alkaline phosphatase levels in Group C were significantly lower than those of Group B(P<0.05);and total protein,total bilirubin and urea in Group C were significantly higher than those of Group B(P<0.05).Pathological observation showed that the alveolar wall was hyperemic,edematous and incrassate;the alveolar epithelium became hyperplastic with neutrophilic;granulocyte infiltrates,the alveolar septum were widened;brain neurons were edematous with perivascular voids;neurons of seahorse were metamorphic and karyopyknotic;and kidney mesangial cells were hyperplastic,both after acute exposure to high altitude and return to the plain area.Conclusion: Blood gas indices,biochemical indicators and the function of heart,liver and kidney are significantly changed;pathological changes in brain,liver,and kidney are dramatic,both after acute exposure to high altitude and return to the plain area.All of these changes will seriously affect pharmacokinetics.