| Objective: â‘ To investigate the dynamic alteration of endothelin-1 (ET-1) in plasma and lung, and the expression of ET-lmRNA, ETAmRNA, ETBmRNA ECEmRNA in lung of asthmatic model in guinea-pigs. To probe the pathologic changes in airways and lung tissues of acute and chronic asthmatic guinea-pig models in guinea-pigs.â‘¡To study the effects of Triptolide(TP) on the dynamic alteration of ET-1 in plasma and lung of asthmatic model in guinea-pigs. To explore the Effects of TP on the alteration of ET-1 , the expression of all these mRNA and the pathologic changes in airways and lung tissues.â‘¢To analysis the relations between ET-1 in lung, the pathologic changes in airways and lung tissues and intervened with TP.Methods: 108 male guinea-pigs were randomly devided into three groups: â‘ Control groups with 48 guinea-pigs, witch was subdivided into normal control group (C0), DMSO control group(CD), asthmatic control group(CA) and asthmatic control group intervened with TP(CT), with 6 guinea-pigs in each subgroup. â‘¢A is asthmatic guinea-pig group with 48 guinea-pigs, witch was subdivided into asthmatic lasting 0 hours subgroup(A0), 2 hours subgroup(A2), 4 hours subgroup(A4), 8 hours subgroup(A8), 12 hours subgroup(A12), 24hours subgroup(A24), 2 weeks time subgroup(A2w) and AB subgroup that were made sensitivity to ovalbin but were not induced to asthma, with 6 guinea-pigs in each subgroup. â‘£T is asthmatic guinea-pig group intervened with TP, with 48 guinea-pigs too, subdivided into asthmatic lasting 0 hours subgroup(T0), 2 hours subgroup(T2), 4 hours subgroup(T4), 8 hours subgroup(T8), 12 hours subgroup(T12), 24 hours subgroup(T24), 2 weeks time subgroup(T2w) and TB subgroup that were made sensitivity to ovalbumin but were not induced to asthma, and also with 6 guinea-pigs in each subgroup, asthmatic model was prepared in three later groups, ET-1 in plasma and lung of asthmatic guinea-pigs was measured by radioimmunoassay. The expressions of ET-1mRNA, ETAmRNA, ETBmRNA and ECEmRNA were measured withreverse transcription DNA polymerase chain reaction (RT-PCR). The pathologic changes in airways and lung tissues were observed under optical and analysised with a computer software of picture-managing. The total and differential white blood cell counts of lung tissues were carried out.Results: We could find all these we were investigating changed with different degree, and we also found Triptolide could inhibit these changes.l.The contents of ET-1 in plasma of A8 groups were significantly higher than thoses in C0, A0.2-4 and CD groups. Furthermore,T8 were significantly higher than T4 too. 2. Compare the content of ET-1 of each groups, the contents of ET-1 of lung tissues in A2,4.8, 12.24 and A2w groups were markly higher than C0 group. To T2.4.8, 12,24 groups, the contents of ET-1 of A2.4.8,12.24 groups were higher. 3. All of the dates were increased after guinea-pigs induced asthma. After first induced asthma, 4 hours ET-1 reached top, but ET-1mRNA,ETAmRNA and ECEmRNA at 2 hours, and markly higher than control group (P<0.01). In two weeks asthma group, all of projects but ECEmRNA increased markly (P<0.01-0.05). TP can inhibited the increasing after 2-8 hours asthma (P<0.01-0.05), and two weeks later all of the projects significantly lower than those in asthma groups. 4. Significant hyperplasia of mucous membrane ,basement membrane, and smooth musle layer of central and peripheral airways in the asthma groups were seen. Significant infiltration of eosinophils and lymphocytes were observed in airways and lung tissues. The total cell number and the number eosinophils and lymphocytes were significantly increased in asthma groups than those in the control group(P<0.01). Neutrophils were dominant at early time, but eosinophils and lymphocytes at late.5. The content of ET-1 of lung tissues in each groups were significantly postive related with the number of total inflammatory cell, lymph cell in lung tissues and the expressions of ET-1mRNA, ETAmRNA, ECEmRNA of lung tissues. (r=0.450, P<0.001; r=0.412, P<0.001... |
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