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

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 hypobaric champer to determine the survival time of mice with decompression hypoxia(min).We observed the activity changes of the mice′s organization carbonic anhydraseⅡ(CAⅡ).By using the drug in prophylaxis,we investigated the effects of carbonic anhydrase target-based inhibitors P-8 for improving the hypoxia tolerance.Results: ①In improving the endurance of mice in the condition of hypoxia,the survival time of 6.25 mg/(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) min,compared with the control group(22.90±3.19) min,the survival time significantly prolonged(P0.05,P0.01);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)min,the survival time significantly prolonged;P-8 groups and Acetazolamide's minimum effective dose were 6.25 and 100 mg/(kg·d),the potency of P-8 is 16 times Acetazolamide.②In 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)min,P0.05];compared with the acetazolamide(23.11±3.71)min,the survival time of high dose of P-8 group was significantly prolonged.③Compared with the normal control group,P-8 [(25 mg/(kg·d),50 mg/(kg·d),100 mg/(kg·d),200 mg/(kg·d)] dose groups inhibited the activity of carbonic anhydraseⅡ(CAⅡ) in the renal(P0.05,P0.01);P-8[100 mg/(kg·d) and 200 mg/(kg·d)] dose group significantly inhibited the activity of carbonic anhydraseⅡ(CA Ⅱ) in the brain(P0.05).Conclusion: P-8 treatment improved the endurance of mice in the condition of hypoxia and worked better than Acetazolamide.The mechanism may be related to the inhibition of carbonic anhydrase organization.