论文部分内容阅读
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 investigate the effects of toluodiazol-amine on hypoxia tolerance in mice and its mechanism. Methods: Healthy Kunming mice were placed in hypoxia bottle, and the time of closed hypoxia was determined. Male Kunming mice were placed in trapezoidal cage and placed in the low-pressure chamber of the small animals for hypobaric hypoxia. The mice were depressurized Hypoxia survival time; observe the activity of carbonic anhydrase Ⅱ (CA Ⅱ) in mice. The prophylactic administration mode was used to study the effect of toluidine azole, a target inhibitor of carbonic anhydrase, on the enhancement of hypoxia endurance. Results: ①There was no significant difference between the two groups (P <0.05) .Conclusion: To improve the airtight hypoxia endurance in mice, tolbutamide 6.25 mg / (kg · d), 12.5 mg / (kg · d), 25 mg / (kg · d) · D), the survival time of the groups of 100 mg / (kg.d), 200 mg / (kg.d) and 400 mg / (kg.d) 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) min, which was significantly longer than that of the blank control group (22.90 ± 3.19) min (P <0.05, P <0.01) 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) min, the survival time was significantly prolonged; the minimum effective doses of toluidine and azetamide were At 6.25 and 100 mg / (kg · d), tazobactam was 16 times more vivax. (2) In the aspects of reducing hypobaric hypoxia and endurance of mice, the survival time of high and low dose of tollzolamide in mice was (24.82 ± 3.92,28.27 ± 5.89) min, which was significantly longer than that in the blank control group [(21.96 ± 2.51) min, P <0.05]. The survival time of high-dose toluidine azole group was significantly prolonged compared with that of acetaminamide group (23.11 ± 3.71) min (P <0.05). (3) Compared with the normal control group, the dosage of tollzolone 25 mg / (kg · d), 50 mg / (kg · d), 100 mg / (kg · d) and 200 mg / (kg · d) (P <0.05, P <0.01). Tolzapine 100 mg and 200 mg could significantly inhibit the activity of CA Ⅱ (P <0.05). CONCLUSION: Tolzapine can enhance the hypoxia endurance and its potency and potency are better than that of acetamide. The mechanism may be related to the inhibition of the activity of carbonic anhydrase.