title: [Effect of neotype carbonic anhydrase target-based inhibitors(P-8) on the hypoxic tolerance in mice].
abstract: 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 anhydrase II (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
  (1) In improving the endurance of mice in the condition of hypoxia, the survival time of 6.25 mg/(kg x 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 (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) min, the survival time significantly prolonged; P-8 groups and Acetazolamide's minimum effective dose were 6.25 and 100 mg/(kg x 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) min, P < 0.05]; compared with the acetazolamide (23.11 +/- 3.71) min, 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 x d), 50 mg/(kg x d), 100 mg/(kg x d), 200 mg/(kg x d)] dose groups inhibited the activity of carbonic anhydrase II (CAII) in the renal (P < 0.05, P < 0.01); P-8 [100 mg/(kg x d) and 200 mg/(kg x d)] dose group significantly inhibited the activity of carbonic anhydrase II (CA II) in the brain (P < 0.05).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Miltary Enviromental Medicine Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China.
authors.forename: Yu-gang
authors.initials: YG
authors.lastname: Shu
authors.forename: Dong-xiang
authors.initials: DX
authors.lastname: Zhang
authors.forename: Zhong-hai
authors.initials: ZH
authors.lastname: Xiao
authors.forename: Wen-yu
authors.initials: WY
authors.lastname: Cui
authors.forename: Hong-jing
authors.initials: HJ
authors.lastname: Nie
authors.forename: Yan-kun
authors.initials: YK
authors.lastname: Zhang
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000532:Altitude Sickness / Q000517:prevention & control*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice
chemical_list: D002257:Carbonic Anhydrase Inhibitors