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To Study Pharmacodynamics And Effect Mechanisms Of Dracocephalum Moldavica L. Total Flavonoids On Bronchial Asthma

Posted on:2014-11-17Degree:MasterType:Thesis
Country:ChinaCandidate:L L YanFull Text:PDF
GTID:2254330401983269Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Object: To study pharmacodynamics and mechanism research of Dracocephalum total flavoesimproving bronchial asthma.Method: To observe the guinea pigs causing asthma incubation period (the time from spray to asthmastarting, breathing difficulties, hyperspasmia until fall) with phosphoric acid histamine and acetylcholinechloride experiments, the effect of antiasthma of Dracocephalum total flavoes on guinea pigs were studied.Bronchial asthmatic model was established by ovialbumin sensitization and long-term inhalationprovocation. Then the rats of each treatment group were dosed dexamethasone, dracocephalum totalflavoes in low, middle and high doses by gavage one time a day and lasting30days, blank control groupwas dosed physiological saline. Using the Flow type integral plethysmography(whole-bodyplethysmography, WBP) system detected the effects on lung function and enhancing breath interval ofasthma rats one hour after last time being dosed; the rats lung tissue being dyed with HE were madepathological section. Using ELISA kits method detected the content of IgE level with asthma rats’ serumand the content of asthma rats’ IL-4, IFN-γ and Eotaxin-1in alveolar perfusion fluid (BALF), the methodalso used to detect the content of collagen typeⅢ(ColⅢ)and transforming growth factor β1(TGF-β1) inasthmatic rat’ lung tissue of each group. The content of asthma rats’ GATA-3protein in lung tissue wasdetected with western blotting.Results:(1) Dracocephalum total flavoes with medium and high dosage groups and positive medicineaminophylline group in asthma incubation period of guinea pigs were obvious longer than blank controlgroup.(2) Asthma model rats appeared obviously difficulty breathing, runny nose, scratching. Lung tissuepathology examination showed that Dracocephalum total flavoes with medium and high dosage group inbronchus and lung tissue in rat lymphocytes and eosinophils around blood vessels such as the degree ofinflammatory cell infiltration getting better than the model group.(3) The respiratory rate (F) in pulmonary function test in the model group increased significantly comparedwith normal group (P <0.01), MVB, PIFB, PEFB significantly decreased (P <0.05or0.01), Ti and Te hasno significant difference (P>0.05). Compared with model group. Dracocephalum total flavoes in mediumand high dose groups and dexamethasone group could reduce the F value of asthma rats (P <0.05or P <0.01), increased the MVB, PIFB and PEFB (P <0.05), but Ti and Te had not significant effect (P>0.05).(4) Airway hyperresponsiveness experiment: compared with normal control group, the Penh of modelgroup increased significantly (P<0.01). Compared with model group, Dracocephalum total flavoes inmedium and high dose groups could significantly reduce Penh (P <0.05or P <0.01). The Penh ofDracocephalum total flavoes in medium and high dose group and dexamethasone group had no significantdifference (P>0.05).(5) IgE determination of content: the model group IgE levels in serum increased significantly (P <0.01) comparing with normal control group. Compare with model group, Dracocephalum total flavoes couldreduce IgE levels in serum with dose dependence (P <0.01). The IgE levels in serum of high dose group ofDracocephalum total flavoes comparing with dexamethasone group had no significant difference (P>0.05)(6) Determination of concentration of IL-4and IFN-γ: compared with normal control group, theconcentration of IL-4levels in BALF in model group rised, IFN-γ density reduced, IL-4/IFN-γ ratioincreased (P <0.01). Compared with model group, Dracocephalum total flavoes with dose dependencecould reduce IL-4levels in BALF, IFN-γ levels rised, the IL-4/IFN-γ ratio decreased (P <0.05or P <0.01). The concentration of IL-4, IFN-γ, and IL-4/IFN-γ ratio in Dracocephalum total flavoes with highdose group had no significant difference (P>0.05) comparing with dexamethasone group.(7) Content determination of Eotaxin-1: compared with normal control group, the content of Eotaxin1inBALF increased significantly in model group (P <0.01). Compared with model group, Dracocephalumtotal flavoes with dose dependent could reduce Eotaxin-1level in rat BALF (P <0.05or P <0.01). TheEotaxin-1content of Dracocephalum total flavoes in high dose group comparing with dexamethasone grouphad no significant difference (P>0.05)(8) ColⅢcontent determination: compared with normal control group, the ColⅢlevel in lung tissue ofmodel group increased significantly (P <0.01); Compared with model group, Dracocephalum total flavoesin medium and high dose groups and dexamethasone group could reduce the ColⅢlevels (P <0.05or P <0.01) in lung tissue. The ColⅢlevel of Dracocephalum total flavoes medium dose group had no significantdifference (P>0.05) comparing with dexamethasone group.(9) TGF-β1content determination: compared with normal control group, the TGF-β1content in lung tissueincreased significantly (P <0.01) in model group. Compared with model group, Dracocephalum totalflavoes in medium and high dose groups and dexamethasone group could decrease the TGF-β1content inlung tissue (P <0.05or P <0.01). The content of TGF-β1in Dracocephalum total flavoes medium dosegroup in comparison with dexamethasone group had no significant difference (P>0.05).(10) Western blotting detecting the lung tissue expression of GATA-3protein: compared with normalcontrol group, the GATA-3expression of lung tissue was significantly higher (P <0.01, n=6) in modelgroup. Compared with model group, Dracocephalum total flavoes in medium and high dose group anddexamethasone group could significantly reduce the lung tissue expression GATA-3(P <0.01, n=6). Thelung tissue GATA-3expression in Dracocephalum total flavoes in medium and high dose group had nosignificant difference (P>0.05) in comparison with dexamethasone group.Conclusion: Dracocephalum total flavoes has obvious effect on Antiasthma of guinea pigs.Dracocephalum total flavoes can improve lung function in rats’ asthma, reduce Penh, and improve asthmaairway hyperresponsiveness. It also can reduce asthma lymphocytes and eosinophils inflammatory cellsinfiltration, inhibit IgE producing, decrease the IL-4/IFN-γ asthma ratio and regulate Th1/Th2immuneimbalance. At the same time, it can reduce the Eotaxin level-1of asthma rats, inhibit the GATA-3proteinexpression, which consequently improve asthma airway chronic inflammation, reduce the content of lung tissue Ⅲ type collagen, inhibit the TGF-β1expression, relieve the airway remodeling process of asthmarats.
Keywords/Search Tags:Bronchial asthma, Dracocephalum Moldavica L, pharmacodynamics, mechanism ofaction
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