本文關(guān)鍵詞： 迷迭香酸 哮喘 氣道炎癥 氧化性肺損傷 抗炎 抗氧化　出處：《廣西大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：哮喘是一種由多種炎癥細(xì)胞和細(xì)胞因子參與調(diào)控的嚴(yán)重危害人和動物健康的慢性氣道炎癥性疾病。迷迭香酸(RA)是一種天然的活性物質(zhì),具有抗氧化、抗炎、抗菌和抗病毒等生物活性。本研究采用卵清蛋白(Ova)誘導(dǎo)建立小鼠過敏性哮喘模型以及用Ova與過氧化氫(H202)聯(lián)合激發(fā)建立小鼠氧化性肺損傷模型,然后考察迷迭香酸對哮喘小鼠的抗炎和抗氧化活性并探索其作用機制,為將來RA在獸醫(yī)臨床上的合理應(yīng)用提供理論依據(jù)。方法:(1)將18-20 g的雌性BALB/C小鼠隨機分為空白對照組、Ova哮喘模型組、RA預(yù)處理組(5、10、20mg/kg)、地塞米松(Dex)預(yù)處理組(2mg/kg)。Ova激發(fā)前一天腹腔注射RA或Dex,末次激發(fā)24h后取小鼠血清、BALF、肺組織進行相關(guān)指標(biāo)測定,以評價RA對哮喘小鼠氣道炎癥的預(yù)防作用;(2)將小鼠隨機分為空白對照組、RA對照組(20mg/kg)、Ova哮喘模型組、RA治療組(20 mg/kg)、Dex治療組。連續(xù)激發(fā)3天后腹腔注射RA或Dex,末次激發(fā)24 h后取樣進行相關(guān)指標(biāo)測定,以評價RA對哮喘小鼠氣道炎癥的治療作用;(3)將小鼠隨機分為空白對照組、RA對照組(40 mg/kg)、Ova對照組、氧化性肺損傷模型組、RA干預(yù)組(10、20、40 mg/kg)、Dex干預(yù)組。Ova和H202聯(lián)合激發(fā)1 h后腹腔注射RA或Dex,末次激發(fā)24 h后取樣進行相關(guān)指標(biāo)測定,以評價RA對氧化性肺損傷小鼠氧化性肺損傷的保護作用。結(jié)果:(1)RA抑制了 Ova誘導(dǎo)的過敏性哮喘小鼠模型氣道炎癥的發(fā)展:明顯減少BALF中炎性細(xì)胞數(shù)目;明顯降低BALF中IL-4、IL-5、IL-13和總蛋白濃度;顯著降低總IgE、Ova-IgE和Eotaxin水平;明顯改善AHR和肺組織病理變化;調(diào)節(jié)MAPK和NF-κB信號通路;抑制AMCase、CCL11、CCR3、Ym2、E-selectin的mRNA的相對表達(dá)水平。(2)RA明顯減輕Ova和H202誘導(dǎo)的過敏性哮喘小鼠模型的氧化性肺損傷:顯著升高肺組織中總SOD總GPx和CAT活性,降低ROS水平;明顯上調(diào)Cu/ZnSOD蛋白和mRNA表達(dá)水平,下調(diào)NOX-2和NOX-4蛋白和mRNA表達(dá)水平;明顯減輕肺組織病理變化;顯著降低IL-4、IL-5、IL-13和總蛋白水平,升高IFN-γ水平。結(jié)論:RA能夠有效的改善過敏性哮喘小鼠氣道炎癥,它的機制可能與阻斷 MAPK(ERK、JNK 和 p38)以及 NF-κB(IκBα 和 p65)相關(guān);RA 可減輕哮喘小鼠的氧化性肺損傷,其機制可能與調(diào)節(jié)NOX-2、NOX-4和Cu/Zn SOD有關(guān)。綜上所述,RA可緩解氣道炎癥、減輕氧化性肺損傷。
[Abstract]:Asthma is a chronic airway inflammatory disease that is regulated by a variety of inflammatory cells and cytokines that seriously endanger human and animal health. Rosemary acid is a natural active substance with antioxidant and anti-inflammatory properties. In this study, an allergic asthma model was established by ovalbumin ovalbumin (Ova) in mice and an oxidative lung injury model was induced by Ova combined with hydrogen peroxide (H202). Then the anti-inflammatory and anti-oxidation activities of rosemary acid on asthmatic mice were investigated and its mechanism was explored. To provide the theoretical basis for the rational application of RA in veterinary clinic in the future. Methods: 1) the female BALB/C mice of 18-20 g were randomly divided into two groups: the control group, the control group, the control group, the RA preconditioning group, the RA preconditioning group and the dexamethasone Dex-preconditioning group, the day before the stimulation. Rats were injected intraperitoneally with RA or Dex.After the last 24 hours of stimulation, the serum of BALF was taken from the mice, and the lung tissues were measured. In order to evaluate the preventive effect of RA on airway inflammation in asthmatic mice, mice were randomly divided into two groups: the RA control group (20 mg / kg) and the RA treatment group (20 mg / kg 路kg ~ (-1)), Dex group. After 3 days of continuous stimulation, RA or Dex2 were injected intraperitoneally for 24 times. H after sampling, the relevant indexes were determined, To evaluate the therapeutic effect of RA on airway inflammation in asthmatic mice, mice were randomly divided into the control group (40 mg / kg) and the control group (40 mg / kg). The model group of oxidative lung injury was injected intraperitoneally with RA or Dex. after combined stimulation of Ova and H202 for 1 h, the rats in RA intervention group were injected with RA or Dex. after 24 h of the last stimulation, the relative indexes were measured. To evaluate the protective effect of RA on oxidative lung injury in mice with oxidative lung injury. Results Ova inhibited the development of airway inflammation in allergic asthmatic mice induced by Ova and significantly reduced the number of inflammatory cells in BALF. The levels of IL-4, IL-5, IL-13, Ova-IgE and Eotaxin in BALF were significantly decreased, the pathological changes of AHR and lung tissue were improved, and the signal pathway of MAPK and NF- 魏 B was regulated. Inhibition of the relative expression level of mRNA of CCL11CCR3Ym2OE-selectin in AMCASE CCL11CCR3Ym2OE-selectin. TRA significantly alleviated the oxidative lung injury induced by Ova and H202-induced allergic asthma in mice: increased the total GPx and CAT activities of total SOD and decreased the level of ROS in lung tissue, and upregulated the expression of Cu/ZnSOD protein and mRNA, and increased the expression of Cu/ZnSOD protein and mRNA in mice with allergic asthma induced by Ova and H202. The expression of NOX-2 and NOX-4 protein and mRNA was down-regulated, the pathological changes of lung tissue were significantly alleviated, IL-5 IL-13 and total protein levels were significantly decreased, and IFN- 緯 level was increased. Conclusion: WRA can effectively improve airway inflammation in allergic asthmatic mice, and decrease the level of IL-5, IL-13 and IL-13, and increase the level of IFN- 緯. Its mechanism may be related to the blocking of MAPK ERKN JNK and p38) and NF- 魏 B, I 魏 B 偽 and p65) related to the reduction of oxidative lung injury in asthmatic mice, and its mechanism may be related to the regulation of NOX-2NOX-4 and Cu/Zn SOD. In conclusion, RA can relieve airway inflammation and alleviate oxidative lung injury.
【學(xué)位授予單位】：廣西大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：S856.3

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