| Objective: The bronchus asthma(hereinafter referred to ast:the asthma), known as one of the four major chronic problems by medicalcommunity worldwide, is a chronic inflammatory disease, characterized byairway hyperresponsiveness. Its primary pathology changes are the infiltratingof eosinophils, mast cells, lymphocytes and macrophages in the airway. Certainprogress has been made in the research of pathogenesis and treatment forasthma in recent years, however, the incidence of asthma has been tendingupwards worldwide, and the effect of conventional treatment is unsatisfactoryon certain medical cases. Therefore, it is tremendously significant to researchthoroughly on the asthma pathogenesis and look for new effective treatments.This thesis discusses the effect of rosiglitazone, the ligands of peroxisomeproliferator activated receptor γ(PPAR γ), on airway smooth muscle contractionin rats with asthma by means of the experiment in vivo and isolated trachealring, and provides new theoretical basis to rosiglitazone application in clinicaltreatment for asthma. Methods1. Seventy five male SD rats were randomlydivided into control group(group A), asthma group (group B) and RSGtreatment group(C group), twenty five of each group, Isolated tracheal rings ofrats, without epithelium, were prepared as group a, group b, and group c.2.Establishment of asthmatic rat model: The first day and the seventh day,peritoneal cavity of rats, in group B and group C, were injected with1ml of 10%ovalbumin, which were made up of10mg ovalbumin and100mg Al(OH)3, dissolved in1ml distilled water. Peritoneal cavity of rats in group Awere injected with distilled water, whose volumes equals to that of group B andgroup C. from the14th day to the30th day, rats in group B and C were trickledwith2mg ml-1ovalbumin50ul into the nostrils, before the collunarium, rats ingroup C were treated in lavage with4mg kg-1hydrochloric acid rosiglitazonediluted in5ml saline. Rats in group B were treated in lavage with equal volumeof saline; simultaneously, rats in group A were treated in collunarium andlavage with equal volume of saline.3. After the last sensitization, the lungtissue of5rats in each group were removed with HE staining, and theeosinophils and lymphocytes were compared, which were in bronchial mucosaand submucosal.4. After the last sensitization, the latent period of asthma inthree groups rats was measured.5. Isolated tracheal rings of rats were placedin a bath filled with Krebs-Henseleit solution,95%O2, and5%CO2at37℃,connected to the polygraph through tension transducer and biological amplifier,and the changes of tracheal ring tension were recorded by using the Chartsoftware:(1)The contraction tension strength which were induced by theconcentration gradient of ACh(0.05mmol L-1,0.5mmol L-1,5mmol L-1) on theisolated tracheal ring in three groups were compared.(2) The relaxing effect onisolated rings in rats from group a and group b, which were precontracted byAcetycholine (ACh) with three different concentration gradient of RSG,0.01mmol L-1(low density),0.1mmol L-1(middle density), and1mmol L-1(high density) was compared.(3) The effect on tracheal rings in group a and group brelaxed by the RSG by using Indomethacin, Methylene blue, Propranolol,L-NAME, and IbTX were observed.(4) The effect on the ACh dose-responsecurves of isolated tracheal rings in rats from group a and group b caused bythree different concentration gradient of RSG,0.01mmol L-1,0.1mmol L-1and1mmol L-1were observed. Results1. Lung tissue HE staining: theinfiltration degree of eosinophils and lymphocytes in bronchial mucosal andsubmucosal in group B were significantly higher than the that in the rest twogroups, and there were significant differences (all P <0.05, n=20).2. Thelatent periods of asthma were group B <group C <group A, and there weresignificant differences,(all P <0.05, n=20).3. Tests for isolated trachealrings:(1) The response rate of tracheal rings in rats from group b, which wasinduced by the concentrations of ACh, was higher than that in rats from group aand c, and there were significant differences (all P <0.05, n=20).(2) Therewas relaxing effect on tracheal rings in rats from group a and group b with theconcentrations gradient of RSG, furthermore, dose-dependent manner, and therewere significant differences (all P <0.05, n=20). However, there were nosignificant differences in the relaxing effect on group a and group c (all P <0.05,n=20).(3) Indomethacin, Methylene blue and Propranolol had no effect on therelaxation, induced by the concentration gradient of RSG to tracheal rings inrats from group a and group b, there were no significant differences (all P>0.05,n=20); L-NAME had blocking effect on the relaxation in rats from group b (all P <0.05, n=20), IbTX had blocking effect on the relaxation, induced by RSG, inrats from group a and group b (all P <0.05, n=20), and the blocking effect ofIbTX on tracheal rings in Group a was more powerful than that on group b(all P<0.05, n=20).(4) With the RSG, ACh dose-response curve of isolated trachealshift significantly to the right side in rats from group a and group b.Conclusions The RSG was able to reduce the infiltration of inflammatorycells in asthmatic rats significantly; it was capable of extending the incubationperiod of asthma, reducing the constriction tension of airway; RSG couldproduce a relaxation on the tracheal rings of rats which was pre-contracted byACh, which was not dependent on Prostacyclin, soluble guanylyl cyclase andβ-adrenergic receptor, but dependent on the Largeconductance calciumactivated potassium channels and NO; The RSG leaded ACh dose-responsecurve of isolated tracheal to shift to the right side in rats from group a andgroup b. |
PDF Full Text Request