Protective Effect And Mechanism Of Ginkgolide B Against Acute Hypobaric Hypoxia Exposure Induced Cognitive Impairment In Rats

Objective:Relying on the platform of artificial experimental cabin at high altitude,the effects of Ginkgolide B（GB）on the function cognitive function of rats,which exposed to acute hypobaric hypoxia were observed and the possible molecular mechanism was discussed.Methods:After 3 days of adaptive feeding,40 male SD rats were stochastically separated into 4 groups:normoxia group（C）,normoxia+ginkgolide B group（C+GB）,hypobaric hypoxia group（HH）,hypobaric hypoxia+ginkgolide B group（HH+GB）,with 10rats in each group.The normoxia+ginkgolide B group and hypobaric hypoxia+ginkgolide B group were given 120mg/kg ginkgolide B by gavage,while the normoxia group and hypobaric hypoxia group were given the isodose normal saline for once a day for 5consecutive days.At the end of the fifth day of administration,except for the normoxia group and normoxia+ginkgolide B group,which were raised in normoxic environment,the rest groups were exposed to low pressure and hypoxia for 7 days in an artificial experimental chamber at a simulated altitude of 6000m.The cognitive function of rats in each group with an assessment by the classic Morris water maze test,and then the rats were killed to take the hippocampal tissue for preparation of homogenate or brain for tissue fixation.Colorimetry was used to detect the concentration of calcium ions in the hippocampus,real-time fluorescence quantitative polymerase chain reaction technology（RT-q PCR）was used to detect the m RNA level of Ca M and Ca MKⅡin the hippocampus,immunohistochemistry was used to detect the expression level of Ca M and Ca MKⅡin the hippocampus,and Western blot was used to detect the expression level of Ca M,Ca MKⅡand its phosphorylated protein p-Ca MKⅡin the hippocampus.Results:1.The Morris water maze results displayed that compared with the normoxia group,the escape latency of rats in the hypobaric hypoxia group was observably prolonged（P<0.01）,and the residence time in the target quadrant and the number of crossing the platform were observably reduced（P<0.05）.Compared with the hypobaric hypoxia group,the escape latency in the hypobaric hypoxia+ginkgolide B group was significantly shortened（P<0.05）,and the residence time in the target quadrant and the number of crossing the platform were significantly increased（P<0.05）.2.The results of calcium colorimetry showed that compared with the normoxia group,the concentration of Ca²⁺in the hippocampus of rats in the hypobaric hypoxia group increased significantly（P<0.01）,Compared with hypobaric hypoxia group,the concentration of Ca²⁺in hippocampus of rats in hypobaric hypoxia+ginkgolide B group decreased significantly（P<0.05）.3.The results of RT-q PCR showed that compared with the normoxia group,the level of Ca M m RNA in the hippocampus of rats in the hypobaric hypoxia group decreased significantly（P<0.01）;Compared with hypobaric hypoxia group,the level of Ca M m RNA in hippocampus of rats in hypobaric hypoxia+ginkgolide B group increased significantly（P<0.05）.4.immunohistochemistry results showed that the expression of Ca M protein in hippocampus of rats in hypobaric hypoxia group was significantly lower than that in normoxia group（P<0.05）;Compared with hypobaric hypoxia group,the expression of Ca M protein in hippocampus of rats in hypobaric hypoxia+ginkgolide B group was significantly up-regulated（P<0.05）there were no significant changes in the expression level of Ca MKⅡprotein in hippocampus of 4groups（P>0.05）.5.Western blot showed that the expression of Ca M and p-Ca MKⅡprotein in hippocampus of rats in hypobaric hypoxia group was significantly lower than that in normoxia group（P<0.01）,Compared with hypobaric hypoxia group,the expression of Ca M and p-Ca MKⅡprotein in hippocampus of rats in hypobaric hypoxia+ginkgolide B group was significantly up-regulated（P<0.01）,there were no significant changes in the expression level of Ca MKⅡprotein in hippocampus of 4 groups（P>0.05）.Conclusion:Acute hypobaric hypoxia exposure can lead to cognitive impairment in rats.Ginkgolide B intervention can effectively regulate the calcium homeostasis balance of hippocampal neurons,alleviate neuronal damage under acute hypoxia by regulating the Ca²⁺/Ca M-Ca MKⅡsignal pathway in the hippocampus,and then improve cognitive impairment in rats caused by acute hypobaric hypoxia exposure.