ABSTRACT
Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate
ABSTRACT
OBJECTIVE:To provide reference for rational use of respiratory inhalants. METHODS:The utilization of respiratory inhalants in 34 hospitals from Nanjing area during 2012-2014 was analyzed by SPSS13.0 software in respects of DDDs,consumption sum,DDC,health insurance and self-paying cost and so on. RESULTS:Respiratory inhalants involved 4 kinds of drugs, 5 kinds of dosage forms,12 kinds of general name and 38 kinds of trade name(specification)in 34 hospitals from Nanjing area during 2012-2014. The total DDDs and total consumption sum of respiratory inhalants increased from 10 827.46×103 and 71,006, 500 yuan in 2012 and 14 627.25×103 and 99,137,100 yuan in 2014,there was no statistical significance(P>0.05). 4 categories of respiratory inhalants in the list of DDDs were anticholinergic agents,compound preparations,glucocorticoid and β2 receptor agonists; DDDs of each type increased year by year,but only that of anticholinergic agents had statistical significance(P0.05). 5 kinds of inhalants in the list of DDDs were aerosol preparation,power aerosols,atomizing solution,nasal spray and clickhaler. DDDs of aerosol preparation and power aerosols increased year by year,with statistical significance(P<0.05). Top one in the list of consumption sum was power aerosols during 2012-2013 and atomizing solution in 2014;power aerosols took up the first place in the list of total consumption in 3 years. Among 12 kinds of general name inhalants,top 4 inhalants in the list of DDDs were ipratropium bromide,salmeterol and fluticasone, albuterol and budesonide,and the constituent ratio of their total DDDs in 3 years were 40.16% ,16.71% ,13.51% and 13.39%,respectively;the sum of constituent ratio of total DDDs in 3 years was more than 80%. Top 3 inhalants in the list of consumption sum were budesonide,salmeterol and fluticasone, budesonide and formoterol,and the sum of constituent ratio of their total consumption sum in 3 years were 39.59%,20.81% and 12.50% ,respectively;the sum of constituent ratio was more than 70% . DDC of salbutamol was the lowest. Among 38 kinds of trade name(specification)inhalants,the type and cost of health insurance accounted for 92.11% and 95.02% .Pulmicort atomization suspension and Symbicort Turbuhaler(160 μg)took up the first place in the list of health insurance cost and self-paying cost respectively,and they were B directory of health insurance. CONCLUSIONS:The utilization of respiratory inhalants was basically reasonable in 34 hospitals from Nanjing during 2012-2014.
