| Objective:To investigate the effect of chronic asthma attack on cognitive and social behavior in maternal immune-activated offspring Balb/c mice and its possible mechanism.Methods:Healthy pregnant Balb/c mice were selected and randomly divided into pregnancy immune-activated group(group A,n=6)and control group(group B,n=3).Group A: Sensitized by intraperitoneal injection of Ovalbumin+Aluminium hydroxide solution(OVA+Alum)in the first,middle and late stages of pregnancy.Group B was intraperitoneally injected with normal saline at the same time.Then the offspring mice in group A were randomly divided into chronic persistent asthma group(group C,n=10)and pregnant control group(group D,n=10).Ten offspring mice from group B were randomly selected as blank control group(group E,n=10).Group C began ultrasonic atomization of 1%OVA solution on the 21 st day after birth,once a day for30 min for 3 consecutive days every week,for 6 weeks.Group D and Group E were treated with ultrasonic atomization of normal saline at the same time point.The behavior of mice during atomization stimulation was observed,and the levels of serum IgE and inflammatory factors IL-6,IL-1β and TNF-α were detected.HE staining,glycogen PAS staining and Masson staining were used to observe the changes of lung airway inflammation,airway mucus and airway remodeling in mice to evaluate whether the model of chronic persistent asthma was established successfully.The social preference of the mice was tested by the three-chamber test,and the Mirrors water maze test was used to test their learning and cognitive ability.The levels of IL-6,IL-1β and TNF-α in serum,lung tissue and hippocampal tissue of brain were detected by ELISA to understand the expression levels of inflammatory mediators in different tissues,and the correlation of the levels of inflammatory factors in different tissues was analyzed.The expression of Ionized calcium binding adapter protein 1(Iba-1)and Inducible nitric oxide synthase(iNOS)protein in hippocampus was studied by Western-Blot to determine whether M1 microglia was activated.Results:1.During atomization,mice in group C showed frequent sneezing and nose scratching,and even significantly accelerated breathing,agitation,abdominal muscle spasm,and fecal incontinence,etc.,while mice in group D and group E only had occasional nose scratching behavior.2.There were obvious inflammatory reactions around the airways in group C,with increased mucus secretion,goblet cell proliferation,airway wall thickening and collagen fiber increase around the airways,while there were no obvious changes in group D and group E.The airway inflammatory cell score,airway smooth muscle thickness,airway mucus score and airway collagen fiber area in group C were significantly higher than those in group D and group E(P<0.05).3.The serum IgE,IL-6,TNF-α and IL-1β levels in group C were significantly higher than those in group D and group E.The levels of inflammatory factors in group D were higher than those in group E(P<0.05).4.Comparing the time of exploring the social room and the non-social room,the time of exploring the social room in group C and group D was less than that in group D(P <0.05);Mice in group E spent significantly longer exploring the former than the latter.The interaction time of mice in groups C and group D to empty cage was longer than that of unfamiliar mice(P<0.05;P=0.022<0.05);The social preference index of group C and group D was significantly decreased,and group C was lower than group D(P<0.05).5.Comparison of water maze test results: there was no difference in escape latency among all groups.In the space exploration experiment,compared with group E,the number of times that mice in group C and group D passed through the original table decreased,and there was a difference.In the comparison of platform quadrant activity time,the activity time of group C and group D was less than that of group E,and group C was less than that of group D(P<0.05).6.The levels of IL-6,TNF-α and IL-1β in the hippocampus and lung tissues of mice: the levels of inflammatory factors in the hippocampus and lung tissues of mice in group C were significantly higher than those in groups D and group E(P<0.05);In addition,the levels of inflammatory factors in the hippocampus and lung tissues of mice in group D were higher than those in group E(P<0.05).7.Correlation analysis of inflammatory factors in serum,lung tissue and hippocampal tissue of the three groups: Il-6 and IL-1β concentrations in group C were positively correlated with hippocampal tissue and serum,lung tissue and serum,hippocampal tissue and lung tissue(P<0.05).TNF-α concentration was positively correlated with serum,hippocampus and lung tissues(P<0.05).There was a positive correlation between the inflammatory factors in the hippocampus and serum in group D(P<0.05).The levels of inflammatory factors in group E showed no correlation between hippocampus and serum,lung tissue and serum,hippocampus and lung tissue.8.The expression of iNOS and Iba1 protein in hippocampus of group C was higher than that of group D and group E(P<0.05).The expression of iNOS and Iba1 protein in hippocampus of group D was higher than that of group E(P < 0.05).Conclusions:Chronic asthma attack in MIA offspring mice has an effect on their cognitive and social behavior changes.The release of pro-inflammatory factors promotes the activation of M1 microglia in the hippocampus,which may be the mechanism of inducing cognitive and social behavior disorders in mice. |
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