碳酸酐酶靶向性抑制剂甲苯磺烷唑胺对机体缺氧耐力的影响  

Effect of neotype carbonic anhydrase target-based inhibitors(P-8) on the hypoxic tolerance in mice

作　　者：舒玉刚[1] 张东祥[1] 肖忠海[1] 崔文玉[1] 聂鸿靖[1] 张延坤[1] 张雁芳[1] 程悦[1] 汪海[1] 

机构地区：[1]军事医学科学院卫生学环境医学研究所全军军事环境医学重点实验室,天津300050

出　　处：《中国应用生理学杂志》2011年第3期276-279,共4页Chinese Journal of Applied Physiology

基　　金：国家科技重大专项军特药创制(2009ZXJ09004-086)

摘　　要：目的:探讨甲苯磺烷唑胺对提高小鼠缺氧耐力的影响及其机制。方法:将健康昆明小鼠放入缺氧装置瓶中,测定密闭缺氧存活时间;将雄性昆明小鼠放入梯形笼中,置于小动物低压舱进行减压低氧,测定小鼠减压低氧存活时间;观察小鼠组织碳酸酐酶Ⅱ(CAⅡ)活性改变。采用预防给药方式,研究碳酸酐酶靶向性抑制剂甲苯磺烷唑胺对提高低氧耐力的作用。结果:①在提高小鼠密闭缺氧耐力方面,甲苯磺烷唑胺6.25 mg/(kg·d)、12.5 mg/(kg·d)、25 mg/(kg·d)、50 mg/(kg·d)、100 mg/(kg.d)、200 mg/(kg.d)和400 mg/(kg.d)剂量组的存活时间分别为(27.38±4.63、29.53±4.43、29.67±7.28、31.55±6.34、32.45±6.65、36.81±7.24和35.41±4.20)min,与空白对照组(22.90±3.19)min比较,显著延长(P<0.05,P<0.01);与同等剂量醋氮酰胺组(24.54±3.17、22.70±3.04、22.67±2.99、23.93±0.96、27.87±5.06、30.79±5.12和35.14±6.46)min比较,存活时间明显延长;甲苯磺烷唑胺和醋氮酰胺最小有效剂量分别是6.25及100 mg/(kg·d),甲苯磺烷唑胺是醋氮酰胺效价的16倍。②在提高小鼠减压低氧耐力方面,甲苯磺烷唑胺中、高剂量组小鼠的存活时间为(24.82±3.92、28.27±5.89)min,明显长于空白对照组[(21.96±2.51)min,P<0.05];高剂量甲苯磺烷唑胺组的存活时间与醋氮酰胺组(23.11±3.71)min比较,明显延长(P<0.05)。③与正常对照组相比,甲苯磺烷唑胺25 mg/(kg·d)、50 mg/(kg·d)、100 mg/(kg.d)和200 mg/(kg·d)剂量组能显著抑制肾碳酸酐酶Ⅱ(CAⅡ)活性(P<0.05,P<0.01);甲苯磺烷唑胺100mg及200mg剂量组能显著抑制脑碳酸酐酶Ⅱ(CAⅡ)活性(P<0.05)。结论:甲苯磺烷唑胺具有提高低氧耐力作用,其效价和效能均优于醋氮酰胺,其机制可能与抑制组织碳酸酐酶活性有关。Objective： To explore the effects of different doses of P-8 in increasing the Hypoxia tolerance of mice and the mechanisms involved. Methods： The health mice were placed into the oxygen deficit bottles and measured the survival time in the condition of hypoxia. The male mice were put into the ladder cage, then placed them into the hypobarie champer to determine the survival time of mice with decompression hypoxia （min）. We observed the activity changes of the mice＇s organization carbonic anhydrase Ⅱ （CA Ⅱ ）. By using the drug in prophylaxis, we investigated the effects of carbonic anhydrase target-based inhibitors P-8 for improving the hypoxia tolerance. Results： （1）in improvng the endurance of mice in the condition of hypoxia, the survival time of 6.25 nag/（ kg·d） and more doses of P-8 groups were （27.38 ± 4.63,29.53±4.43,29.67 ±7.28,31.55±6.34,32.45±6.65, 36.81 ±7.24 and 35.41 ±4.20） rain, compared with the control group （22.90 ± 3.19） min , the survival time significantly prolonged （P 〈 0.05, P 〈 0.01 ）; compared to the same dose of acetazolamide groups （24.54±3.17, 22.70±3.04, 22.67±2.99, 23.93±0.96, 27.87±5.06, 30.79±5.12 and 35.14±6.46）rain, the survival time sig- nificantly prolonged; P-8 groups and Aeetazolamide＇ s minimum effective dose were 6.25 and 100 mg/（kg·d）, the potency of P-8 is 16 times Acetazolamide. （2）In improving the endurance of mice in the condition of hypoxia, the survival time of middle and high doses of P-8 groups [ （ 24.82 ± 3.92,28.27 ± 5.89） min ] were significantly longer than those in control group [ （21.96 ± 2.51 ） rain, P 〈 0.05 ] ; compared with the acetazolamide（23.11 ± 3.71）rain, the survival time of high dose of P-8 group was significantly prolonged. （3）Compared with the normal control group, P-8 [（25 mg/（kg·d）, 50 mg/（kg·d）, 1130 mg/（kg·d）, 200 mg/（kg·d）] dose groups inhibited the activity of earbonic anhydrase Ⅱ （CAⅡ） in the renal （P 〈 0.05, P �

关 键 词：甲苯磺烷唑胺 醋氮酰胺 碳酸酐酶Ⅱ 低氧耐力 

分 类 号：R977.7[医药卫生—药品]