醋甲唑胺干预对急进高原大鼠的损伤保护作用

Protective Effects of Methazolamide on Acute Exposure to High Altitude

目的探究急进4 300 m高原对Wistar大鼠机体血气生化改变、病理变化、血清肿瘤坏死因子-α和白细胞介素-1β影响及醋甲唑胺干预对大鼠高原损伤的保护作用。方法将28只成年健康Wistar大鼠按体重随机分为平原(海拔55米)对照组、高原(海拔4 300 m)模型组、醋甲唑胺组、乙酰唑胺组,分别灌胃给予0.9%氯化钠注射液、醋甲唑胺(每日2次,剂量为2.23 mg·kg-1)和乙酰唑胺(每日2次,剂量为22.33 mg·kg-1),对大鼠进行生化、血气分析、病理比较,并检测所得血清样品肿瘤坏死因子-α和白细胞介素-1β含量。结果血气、生化和病理结果显示,高原组大鼠出现脱水症状,与平原对照组比较,高原模型组各指标变化显著(P<0.01),与高原模型组比较,醋甲唑胺组和乙酰唑胺组门冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)、酸碱度(p H)、碳酸氢根离子浓度、缓冲碱(BB)、剩余碱(BE)等指标显著下降(P<0.01),总蛋白(TP)、尿素(UREA)、二氧化碳分压(Pa CO2)、钠离子浓度、氯离子浓度等指标显著上升(P<0.01),表明两组均出现代谢性酸中毒合并呼吸性碱中毒,且肝肺组织出现病理性损伤,其中,与乙酰唑胺组比较,醋甲唑胺组损伤较小。与平原对照组相比,高原组血清肿瘤坏死因子-α显著性升高,白细胞介素-1β显著性降低,其中,乙酰唑胺组和醋甲唑胺组血清肿瘤坏死因子-α、白细胞介素-1β含量均显著高于模型组(P<0.01)。结论醋甲唑胺能改善急进高原大鼠的生理生化状况,减轻炎症损伤,具有较好的缺氧保护作用。

OBJECTIVE To investigate the effect of acute exposure to 4 300 m altitude environments on the body pathophysiological, serum, TNF-α and IL-1βα of Wistar rats and protective effect of methazolamide on Wistar rats. METHODS Twenty-eight Healthy adult Wistar rats were randomly divided into plain（ altitude of 55 m） control group, high altitude（ altitude of 4 300 m） model group, high altitude nlethazolamide group, and high altitude acetazolamide group. After being intragastric administration with 0. 9% so- dium chloride injection, methazolamide（2 times a day, 2. 23 mg ·kg^-1 ） and acetazolamide（2 times a day, 22.33 mg· kg^-1 ） for 5 consecutive days. The biochemical, blood gas, the pathological results of rats were analyzed. The TNF-α and IL-1β content were de- tected from the blood samples. RESULTS Blood and biochemical results showed the high altitude might cause dehydration in rats. Compared with the plain control group, each index of the high altitude model group changed significantly（ P 〈 0. 01 ） , compared with the high altitude group, the aspartate transaminase （AST）, alanine aminotransferase （ALT）, pH value, bicarbonate concentration （ cHCO3 - ） , buffer base（BB） , base excess（BE） of methazolamide and acetazolamide group were significantly decreased （ P 〈 0. 01 ） , indicated that methazolamide and aeetazolamide had protective effect on rat liver. The total protein（TP） , urea solution（UREA） , par- tial pressure of carbon dioxide （ PaCO2 ） , sodium concentration （ cNa ＋ ） , chloride concentration （ eCl- ） were significantly increased （ P 〈 0. 01 ） , indicated that the high altitude group had metabolic acidosis and respiratory alkalosis, and liver and lung tissue had path- ological damaged. Compared with the acetazolamide group, the methazolamide group damaged less. Compared with plain control group, serum TNF-α of high altitude groups significantly increased, IL-1β of high altitude groups decreased significantly, which, serum TNF-α, IL-1β levels of aeetazolamide and methazolamide group were significantly higher than high altitude model group（ P 〈0.01 ）. CON- CLUSION Methazolamide can improve acute high altitude physiological and biochemical status of rats, reduce inflammatory injury, with a good protective eft）ct of hypoxia.