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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。
OBJECTIVE: To observe the changes of various factors affecting the pharmacokinetic parameters of Wistar rats after they reached the plateau rapidly and returned to the plain rapidly. Methods: Twenty-one Wistar rats were randomly divided into three groups. Blood samples were collected from the orbital of rats in plain areas (55 m in Shanghai, 4010 m in Maqu, Gansu Province) Indicators, abdominal aorta blood for blood gas analysis, complete brain, lung, kidney pathological changes after the study. Results: Compared with the plain group, the pH value, buffer alkali, alkali excess, total carbon dioxide, arterial oxygen saturation, arterial partial pressure of oxygen, serum sodium ion concentration, lactate dehydrogenase and total protein were significantly decreased (P <0.05). The arterial partial pressure of carbon dioxide, serum chloride concentration, total bilirubin and alkaline phosphatase were significantly increased (all P <0.05). Compared with the plain group, , Base excess, arterial oxygen saturation, arterial partial pressure of oxygen, hemoglobin, serum sodium ion concentration, lactate dehydrogenase and total protein were significantly decreased, arterial carbon dioxide partial pressure, serum chloride concentration, alanine aminotransferase , Total bilirubin and urea (all P <0.05). The levels of hemoglobin and alkaline phosphatase in the returned plains and the plateau group were significantly lower (all P <0.05) Urea significantly increased (all P <0.05). The pathological results showed that the alveolar wall thickening, hyperemia, edema, alveolar epithelial hyperplasia, alveolar septum widening and neutrophil infiltration were observed in both the plateau group and the plateau group returning to the acute plateau; the edema of the cerebral neurons and the perivascular space Formation, degeneration of hippocampal neurons, nuclear pyknosis; mesangial cell proliferation. CONCLUSION: The blood gas indexes, biochemical indexes and the functions of heart, liver and kidney all changed significantly in rats in the plateau and the plateau returning to the plain. The pathological changes were obvious in the brain, lung and kidney, which seriously affected the pharmacokinetic parameters of the drugs.