ABSTRACT
Objective To study the mechanism of NS1619 on airway remodeling in asthmatic mice. Methods A total of 24 healthy female BALB/c mice were randomly divided into 3 groups:the control group, the oval albumin (OVA) group (the asthma group) and the NS1619 group (the intervention group), 8 mice in each group. Asthma group was induced with OVA, chal-lenged by continuous inhalation with 5%OVA from day 19 to 23, then changed to 3 times per week from day 24 to 55. Interven-tion group was inhaled with NS1619 (30μmol/L) before OVA. Control group was given with normal saline. The thickness of air-way smooth muscle and the area of collagen deposition in lung tissue slices were observed by HE and Masson staining, measured by a computer assisted image analysis system. The concentration ofα-smooth muscle actin (α-SMA) in cells was detected by immunohistochemistry. The expression of platelet derived grouth factor-BB, PDGF-BB (PDGF-BB) in serum was measured by immunosorbent assay. Results Compared with the asthma group, the pathologic changes of lung tissue, the thickness of airway smooth muscle and collagen deposition in the group treated with NS1619 were signiifcantly decreased (P<0.05). Compared with the asthma group, the levels ofα-SMA in cells and PDGF-BB in serum in NS1619 treated group were signiifcantly decreased (P<0.05). Conclusions NS1619 partly inhibited airway remodeling in asthmatic mice, partially by down-regulating the expres-sion level ofα-SMA and PDGF-BB.
ABSTRACT
Loss of synaptic transmission and accumulation of extracellular K+((K+)o) are the key features in ischemic brain damage. Here, we examined the effects of several K+ channel modulators on the early ischemic changes in population spike (PS) and (K+)o in the CA1 pyramidal layer of the rat hippocampal slice using electrophysiological techniques. After onset of anoxic aglycemia (AA), orthodromic field potentials decreased and disappeared in 3.3 +/- 0.22 min (mean +/- SEM, n = 40). The hypoxic injury potential (HIP), a transient recovery of PS appeared at 6.0 +/- 0.25 min (n = 40) in most slices during AA and lasted for 3.3 +/- 0.43 min. (K+)o increased initially at a rate of 0.43 mM/min (Phase 1) and later at a much faster rate (12.45 mM/min, Phase 2). The beginning of Phase 2 was invariably coincided with the disappearance of HIP. Among K+ channel modulators tested such as 4-aminopyridine (0.03, 0.3 mM), tetraethylammonium (0.1 mM), NS1619 (0.3 ~ 10 muM), niflumic acid (0.1 mM), glibenclamide (40 muM), tolbutamide (300 muM) and pinacidil (100 muM), only 4-aminopyridine (0.3 mM) induced slight increase of (K+)o during Phase 1. However, none of the above agents modulated the pattern of Phase 2 in (K+)o in response to AA. Taken together, the experimental data suggest that 4-aminopyridine-sensitive K+ channels, large conductance Ca2+/-activated K+ channels and ATP-sensitive K+ channels may not be the major contributors to the sudden increase of (K+)o during the early stage of brain ischemia, suggesting the presence of other routes of K+ efflux during brain ischemia.