1.Effects of sodium butyrate on asthma in aged and young mice
Hanyu LI ; Ange WANG ; Shumin LI ; Qin ZHANG
Chinese Journal of Geriatrics 2022;41(11):1365-1370
Objective:To compare the effects of sodium butyrate(Sob)on aged and young asthmatic mice.Methods:Male C57BL/6 mice aged 24 months(n=18)and 4 months(n=18)were divided using randomly generated numbers into 3 groups: a control group, a model group(treated with ovalbumin, OVA), and a treatment group(OVA+ Sob), with 6 mice in each group.The control group was given normal saline as the blank control.Two days before the OVA challenge, the treatment group was given 1 mg/g Sob by intraperitoneal injections and the OVA+ Sob group and the control group were given normal saline intervention.Endpoint evaluation was performed 1 day after the last challenge.Differences in airway hyperresponsiveness(AHR), pathological manifestations of lung tissue sections stained with hematoxylin eosin(HE), and inflammatory factors in lung tissues were compared between aged and young mice and the effects of Sob on asthmatic mice of different ages were evaluated.Results:Under the stimulation of methacholine(Mch), AHR of the O-OVA group was significantly higher than that of the Y-OVA group(6.250 g/L: 276.28±113.62 vs.103.02±19.55, t=3.368, P=0.026; 12.500 g/L: 457.5±157.29 vs.114.76±20.28, t=4.338, P=0.022; 25.000 g/L: 1113.16±256.98 vs.567.87±187.34, t=3.538, P=0.009). HE staining revealed that, compared with the Y-control group, the O-control group exhibited a reduced area of alveolar cavity, partial lung consolidation, proliferation of interstitial fibrous connective tissues, alveolar epithelial cells and capillary endothelial cells.Compared with its control group, the O-OVA group had significantly elevated levels of eotaxin( P=0.035), IL-17A( P=0.004)and IL-1β( P=0.001), among the inflammatory factors, whereas the Y-OVA group had elevated levels of eotaxin( P=0.001), IL-17A( P=0.001), IL-4( P=0.004), KC( P=0.012)and IL-1β( P<0.001). Compared with the O-OVA group, the Y-OVA group had increased levels of IL-4( Z=2.882, P=0.004)but decreased levels of IL-1β( t=2.728, P=0.020). As for the effects of Sob on asthmatic mice of different ages, AHR of the O-OVA+ Sob group was significantly alleviated with stimulation of 12.500 g/L Mch( P=0.015)and 25 g/L Mch( P=0.014), compared with the O-OVA group.With stimulation of 3.125 g/L Mch, AHR of the Y-OVA+ Sob group was significantly decreased( P=0.021)and levels of IL-4( P=0.004)and IL-1β( P=0.014)were significantly reduced in the Y-OVA+ Sob group, compared with the Y-OVA group. Conclusions:The severity of asthma in aged mice is greater than in young mice, perhaps as a result of different immunophenotypes; The alleviating effects of Sob on inflammatory factors in young asthmatic mice may be related to mild AHR in young asthmatic mice, compared with aged asthmatic mice.