Effect Of The Appropriate Dose Of 1,25-?OH?₂D₃ On Airway Remodeling Of Asthma Rat Mode And HMGB1?IL-1? In Lung During Pregnancy And Lactation Period

Objectives:1.To observe the expression of high mobility group box protein 1?HMGB1??interleukin-1??IL-1??, the indexes of airway remodeling in asthmatic rats, and the change of eosinophil cells numbers in bronchoalveolar lavage fluid?BALF? at different stages, in order to investigate the the role of HMGB1?IL-1? in the pathogenesis of asthma rats and discuss the correlation of them.2.To detect the expression of HMGB1?IL-1? and airway remodeling in lung of offspring asthmatic rats after being given appropriate dose of 1,25-dihydroxyvitamin D3?1,25?OH?₂D₃? during pregnancy and lactation period,in order to investigate the effect of appropriate 1,25?OH?₂D₃ on airway remodeling and the potential mechanisms in asthma rats. Methods:According to the proportion of 2:1,compsited female Spraque-Dawley rats and male rats into the same cage. The first day of pregnancy of female rats were confirmed when the vaginal plug appears and pregnant rats were successfully made. The twelve pregnant rats were randomly divided into a group?b group and c group.The rats in c group were treatment with 1,25?OH?₂D₃?10?g/kg? every other day by intragastric administration from the 7st day of pregnancy to 21 st day after birth in offspring rats.While the rats in b group and c group were given the normal saline instead. 24 offspring rats in each group were chosen randomly, then A?control? group?B?asthma? group?C?Vit D? group were set correspondingly. The asthma group and Vit D group were sensitized and challenged with ovalbumin?OVA? to establish the asthmatic rat model, the control group was replaced by normal salin. Then the pulmonary inflammatory was observed by HE, the airway remodeling was measured by image analysis software system, the expression of HMGB1 and IL-1? in lung tissue was detected by immunity histochemistry, the percentage of Eos was evaluated by collecting the BALF. Results:1.The change of lung histopathology: compared with the control group, there were a few inflammatory cells infiltration in the Vit D group which had mild hyperplasia of airway wall area and smooth muscle area, slight luminal stenosis,but worse in asthma group.2.The expression of HMGB1?IL-1? in lung issue:the HMGB1 and IL-1? were bothl expressed in lung tissue of three groups, and the expression of HMGB1 and IL-1? increased after 2 weeks and growed at time dependent?6weeks>4weeks>2weeks?, the difference was statically significant?P<0.01?.The expression of HMGB1?IL-1? was higher than the control group at the three time point?P<0.01?. Compared with the Vit D group the expression of HMGB1?IL-1? decreased in control group?P<0.01?,while increased in asthma group?P<0.01?3.The change of the percentage of eosinophil?Eos? increased in BALF: the percentage of Eos was gradually increased in asthma and Vit D group,6weeks>4weeks>2weeks, the difference was statically significant?P<0.01?,the percentage of Eos in asthma group exceeded the control group at all time?P<0.01?. The percentage of Eos in Vit D group was lower than asthma group?P<0.01?,but was still higher than the control group.4.The index of bronchial wall?Wat/Pbm? and bronchial smooth muscle?Wam/Pbm?:the thickness of Wat/Pbm and Wam/Pbm in ashtam group were significantly higher than the control group at all time?P<0.01?;As the time prolonged,the thickness was higher in asthma group,6weeks>4weeks>2weeks, the difference was statically significant?P<0.01?.The thickness of Wat/Pbm, Wam/Pbm in Vit D group was lower than asthma group?P<0.01?,but still higher than the control group.5.The correlation analysis in asthma group:the expression of HMGB1 and IL-1? in lung tissue were positively correlated at the second?fourth and sixth week?r=0.723, 0. 769,0.746,p<0.05?;the expression of HMGB1 and the percentage of Eos in BALF were positively correlated at the second?fourth and sixth week?r=0.841, 0.857,0.845,p<0.05?;the expression of HMGB1 and Wat/Pbm were positively correlated IX at the second?fourth and sixth week?r=0.789, 0.818,0.809,p<0.05?;the expression of HMGB1 and Wam/Pbm were positively correlated at the second?fourth and sixth week?r=0.781, 0.792,0.773,p<0.05?? Conclusion:1. Airway remodeling exsited in asthma rats and the levels of airway remodeling increased with the time prolonged.2. As the time went on, the expression of HMGB1 and IL-1?, the percentage of Eos in BALF increased more obviously in asthma rats, indicating that HMGB1?IL-1? and the percentage of Eos played a role in the occurrence and development of asthma.3. The expression of HMGB1 is positively correlated with the degree of airway remodeling?the percentage of Eos, suggesting that HMGB1 is one of pathogenic factors that promote the airway remodeling in asthma.;Interaction between HMGB1 and IL-1? which both involved in the pathogenesis of asthma.4. The airway inflammation and airway remodeling in asthmatic rats was relieved by intervention of suitable dose of 1,25?OH?₂D₃ in pregnancy and lactation period.5. 1,25?OH?₂D₃ may retart the progression of asthma by regulating the secretion of HMGB1 and IL-1?.