Effect of four drug-loaded hydrogels on prevention of hypoxic brain damage / 国际药学研究杂志

ABSTRACT

Objective: To investigate the preventive effect of puerarin-,geonone(G20)-,timosaponin BⅡ- and cannabidio(l CBD)-loaded nasal hydrogels on the hypoxic brain injury in mice. Methods: The drug-loaded 4 hydrogels were prepared with poloxamer 407 and poloxamer 188. The healthy adult male SPF BALB/c mice were randomly divided into seven groups(n=5)the normal group,saline(NS)group,blank hydrogel group,puerarin hydrogel group,G20 hydrogel group,timosaponin BⅡhydrogel group and CBD hydrogel group. After 8 days of continuous nasal administration, the anti-hypoxia activity was assayed by the airtight hypoxia test at atmospheric pressure,by recording the survival time of the mice in the test conditions. Meanwhile,the peripheral blood cell counts,pathological changes in the mouse brain tissue and the expression of hypoxia inducible factor-1α(HIF-1α)in the cerebral hippocampal area were also examined. Results The G20 and CBD hydrogels could significantly prolong the survival time of mice in the airtight hypoxia test (P<0.01 and P<0.05),and the red blood cel(l P<0.01 and P<0.05)and hemoglobin counts(P<0.05 and P<0.05) in the mouse peripheral blood were significantly higher in the G20 and CBD hydrogel groups than those in the NS group, indicating that the G20 and CBD hydrogels could increase oxygen-carrying capacity of the peripheral blood in mice. The G20 and CBD hydrogels reduced inflammatory cells in the brain tissues of mice,and mice cell pyknosis and hyperchro- mism,suggesting that G20 and CBD could alleviate the brain injury caused by hypoxia. The immunohistochemistry analysis results for the brain tissue slides of mice showed that the HIF-1α expression in the cerebral hippocampal area in the G20 group was significantly decreased(P<0.01)to the similar level of the normal group. Conclusion: The G20 nasal hydro- gels showed a good anti-hypoxia effect to prevent hypoxic brain injury in the hermetic hypoxia mice model at atmospheric pressure. The mechanism was likely related to the improvement of antioxidant capacity of the body as well as the free radi- cal scavenging and nerve cell protecting effect of G20.