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中藥川貝母對(duì)哮喘模型小鼠MMP-2,MMP-9和TIMP-1的影響

發(fā)布時(shí)間:2018-08-22 13:25
【摘要】:觀察中藥川貝母對(duì)哮喘模型小鼠氣道重塑及基質(zhì)金屬蛋白酶-2(MMP-2)、基質(zhì)金屬蛋白酶-9(MMP-9)與基質(zhì)金屬蛋白酶組織抑制劑-1(TIMP-1)的影響,探討其治療哮喘的作用機(jī)制。BALB/C小鼠,隨機(jī)分為正常組、模型組、高劑量組、低劑量組、陽(yáng)性對(duì)照組。除正常組外,其他各組用卵蛋白(OVA)建立哮喘小鼠模型。造模成功后高劑量組和低劑量組分別按18.0,9.0 mg·kg-1劑量給予中藥川貝母灌胃;陽(yáng)性對(duì)照組于腹腔注射0.5 mg·kg-1劑量地塞米松;正常組和模型組等量生理鹽水灌胃,每天1次,連續(xù)28 d。觀察各組小鼠氣道反應(yīng)性的變化,支氣管肺泡灌洗液(BALF)中細(xì)胞總數(shù)和白細(xì)胞分類(lèi)的變化以及支氣管管壁厚度和支氣管平滑肌厚度的變化;ELISA法檢測(cè)MMP-2,MMP-9,TIMP-1水平;RT-PCR檢測(cè)MMP-2,MMP-9,TIMP-1 mRNA的表達(dá)。結(jié)果顯示,模型組氣道反應(yīng)性、BALF中細(xì)胞總數(shù)以及中性粒細(xì)胞、巨噬細(xì)胞、淋巴細(xì)胞和嗜酸性粒細(xì)胞計(jì)數(shù)、支氣管管壁厚度和支氣管平滑肌厚度明顯高于正常組(P0.01),高劑量組和低劑量組與陽(yáng)性對(duì)照組則明顯低于模型組(P0.05或P0.01);模型組MMP-2,MMP-9和TIMP-1水平和mRNA表達(dá)明顯高于正常組(P0.01),高劑量組和低劑量組與陽(yáng)性對(duì)照組則明顯低于模型組,差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。推斷中藥川貝母可改善哮喘模型小鼠氣道重塑狀態(tài),其機(jī)制可能與其降低MMP-2,MMP-9和TIMP-1有關(guān)。
[Abstract]:Objective: to observe the effects of Chinese traditional Chinese medicine Chuanbei on airway remodeling, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in asthmatic mice. Model group, high dose group, low dose group, positive control group. The asthmatic mice were established by using ovalbumin (OVA) in other groups except the normal group. After the establishment of the model, the high dose group and the low dose group were perfused with the dose of 18.0 ~ 9.0 mg kg-1, respectively; the positive control group was intraperitoneally injected with 0.5 mg kg-1 dexamethasone; the normal group and the model group were given the same amount of normal saline once a day for 28 days. The changes of airway reactivity, the changes of total cell count and leukocyte classification in bronchoalveolar lavage fluid (BALF) and the thickness of bronchial wall and bronchial smooth muscle were observed. The level of MMP-2MMP 9 and TIMP-1 was detected by Elisa and the expression of TIMP-1 mRNA in MMP-2 MMP-9 and TIMP-1 was detected by RT-PCR. The results showed that the total number of cells in airway reactive BALF and the counts of neutrophils, macrophages, lymphocytes and eosinophilic granulocytes in the model group. The thickness of bronchial wall and the thickness of bronchial smooth muscle were significantly higher than that of normal group (P0.01), the levels of MMP-2 MMP-9 and TIMP-1 and the expression of mRNA in model group were significantly higher than those in normal group (P0.01), while those in high dose group, low dose group and positive control group were significantly lower than those in model group (P0.05 or P0.01). The high dose group, low dose group and positive control group were significantly lower than the model group. The difference was statistically significant (P0.01). It is inferred that Chuanbei can improve airway remodeling in asthmatic mice, and its mechanism may be related to the decrease of MMP-2, MMP-9 and TIMP-1.
【作者單位】: 牡丹江醫(yī)學(xué)院;牡丹江醫(yī)學(xué)院附屬紅旗醫(yī)院;
【基金】:黑龍江省自然科學(xué)基金項(xiàng)目(H201490)
【分類(lèi)號(hào)】:R285.5;R-332

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