【摘要】：目的 觀察FIZZ1和腫瘤壞死因子α（TNF-α）在慢性阻塞性肺疾病大鼠中表達(dá)水平的動(dòng)態(tài)變化，探討兩者在慢性阻塞性肺疾病中的作用，同時(shí)探討黃芪甲苷（AST）治療COPD的可能機(jī)制。 方法 雄性SD大鼠108只隨機(jī)分為4組：正常對(duì)照組(A組)18只，COPD模型組30只(B組，分為模型二周組、四周組、八周組各10只)，黃芪甲苷低劑量組30只(C組，分為黃芪甲苷低劑量二周組、四周組、八周組各10只)，黃芪甲苷高劑量組30只(D組，分為黃芪甲苷高劑量二周組、四周組、八周組各10只)。B,C,D組采用每天熏吸香煙和氣管內(nèi)2次滴加脂多糖(LPS)聯(lián)合刺激方法制作大鼠COPD模型，同時(shí)C,D組在每次熏吸香煙前30min予以黃芪甲苷1mL灌胃(用1%羧甲基纖維素鈉溶解，分別含黃芪甲苷3mg,9mg)，A,B兩組同時(shí)用助溶劑羧甲基纖維素鈉1mL灌胃。經(jīng)上述處理后，分別于二周、四周、八周3個(gè)時(shí)間段處死大鼠，常規(guī)病理切片觀察各組各時(shí)間點(diǎn)大鼠氣道和肺組織的形態(tài)學(xué)變化，免疫組織化學(xué)法檢測(cè)肺組織中FIZZ1、TNF-α蛋白水平，RT-PCR法檢測(cè)肺組織中FIZZ1、TNF-α mRNA的表達(dá)情況。 結(jié)果 1、大鼠肺組織病理變化情況 正常對(duì)照組氣道管壁結(jié)構(gòu)完整，周圍無(wú)炎癥細(xì)胞浸潤(rùn)，肺泡結(jié)構(gòu)形態(tài)未見破壞；COPD模型二周組氣道壁及平滑肌增厚，氣道上皮受損，部分纖毛脫落，氣道周圍及肺泡間隔內(nèi)有大量炎癥細(xì)胞浸潤(rùn)；COPD模型四周組與二周組相比，氣道壁及平滑肌明顯增厚，管腔相對(duì)變窄，部分肺泡破壞、融合，肺泡腔擴(kuò)大，仍有炎性細(xì)胞浸潤(rùn)；COPD模型八周組與四周組相比，氣道壁及平滑肌增厚更明顯，管腔更窄，大部分肺泡破壞、融合，肺泡腔擴(kuò)大，，肺泡間隔斷裂。經(jīng)黃芪甲苷干預(yù)后，與同時(shí)間段的COPD模型組相比，氣道管腔狹窄程度和肺泡結(jié)構(gòu)破壞程度有減輕，且黃芪甲苷高劑量組減輕越明顯。 2、大鼠肺組織FIZZ1、TNF-α mRNA和蛋白的表達(dá)水平 FIZZ1、TNF-α mRNA和蛋白在正常肺組織中表達(dá)較弱，COPD模型組FIZZ1、TNF-αmRNA和蛋白隨著刺激時(shí)間的延長(zhǎng)，表達(dá)呈增加趨勢(shì)，均高于對(duì)照組（P0.05）；COPD模型二周組支氣管肺組織中FIZZ1、TNF-α mRNA和蛋白表達(dá)水平增加，四周組FIZZ1、TNF-α mRNA和蛋白表達(dá)水平升高較明顯，兩者相比，差異有顯著性（P0.05）；八周組其表達(dá)水平進(jìn)一步升高，與四周組相比，差異有顯著性（P0.05）；經(jīng)黃芪甲苷干預(yù)后，與同一時(shí)間段的COPD模型二周、四周、八周組比較，F(xiàn)IZZ1、TNF-α mRNA和蛋白表達(dá)水平均有下降，且黃芪甲苷高劑量組較低劑量組下降較明顯，差異有顯著性（P0.05）； 結(jié)論 1、FIZZ1、TNF-α在慢性阻塞性肺疾病大鼠模型中呈動(dòng)態(tài)變化過(guò)程，可能參與了COPD的發(fā)生發(fā)展過(guò)程。 2、黃芪甲苷能減輕COPD氣道炎癥和重塑，延緩COPD的進(jìn)程，且呈量效相關(guān)性，其機(jī)制可能與下調(diào)FIZZ1、TNF-α的表達(dá)有關(guān)。
[Abstract]:Objective to observe the dynamic changes of FIZZ1 and tumor necrosis factor 偽 (TNF- 偽) expression in chronic obstructive pulmonary disease (COPD) rats, and to explore the role of them in chronic obstructive pulmonary disease (COPD). To explore the possible mechanism of astragaloside (AST) in the treatment of COPD. Methods 108 male SD rats were randomly divided into 4 groups: normal control group (group A, n = 18), COPD model group (group B, n = 30), model group (n = 10, n = 10) and low-dose group (group C, n = 30). Astragaloside A (Astragaloside A) group (n = 10) was divided into four groups (n = 10) and Astragaloside A group (n = 30, n = 10, n = 10). In group D, the rat model of COPD was established by cigarette smoking and intratracheal administration of lipopolysaccharide (LPS) twice a day, and the rats in group C were treated with 30min (1% carboxymethyl cellulose sodium dissolved) before each cigarette smoking. Astragaloside A (3 mg / g) and group A B were given intragastric administration with sodium carboxymethylcellulose (1mL) as a cosolvent at the same time. After the above treatment, the rats were killed at 3 times of 2, 4 and 8 weeks, respectively. The morphologic changes of airway and lung tissues were observed by routine pathological sections and FIZZ1, in lung tissues were detected by immunohistochemical method. The level of TNF- 偽 protein and the expression of FIZZ1,TNF- 偽 mRNA in lung tissue were detected by RT-PCR method. Results 1. The pathological changes of lung tissue in the control group were characterized by intact airway wall structure, no infiltration of inflammatory cells and no destruction of alveolar structure. In COPD model group, the airway wall and smooth muscle were thickened, airway epithelium was damaged, some cilia were removed, and a large number of inflammatory cells were infiltrated around the airway and in the alveolar septum. Compared with the two-week group, the airway wall and smooth muscle were thicker, the lumen became narrower, some alveoli were destroyed, fused, the alveolar cavity was enlarged, and inflammatory cells were still infiltrated. Compared with the four groups, the airway wall and smooth muscle were thicker, the lumen was narrower, most of the alveoli were destroyed, fused, the alveolar cavity was enlarged and the alveolar septum was broken. Compared with the COPD model group at the same time, the degree of airway stenosis and the destruction of alveolar structure were reduced after the intervention of Astragaloside, and the more obvious was the abatement in the high dose group of Astragaloside A. 2, the expression level of FIZZ1,TNF- 偽 mRNA and protein in rat lung tissue was weak in normal lung tissue. FIZZ1,TNF- 偽 mRNA and protein expression in COPD model group increased with the prolongation of stimulation time. All of them were higher than the control group (P0.05). The expression of FIZZ1,TNF- 偽 mRNA and protein in bronchopulmonary tissue was increased in COPD model group for two weeks, and the expression level of FIZZ1,TNF- 偽 mRNA and protein in four groups was significantly higher than that in control group (P0.05). The expression level of eight-week group was further increased compared with the four-week group the difference was significant (P0.05). After the intervention of Astragaloside A, the expression of FIZZ1,TNF- 偽 mRNA and protein decreased significantly in the high dose group than in the low dose group, compared with the two, four and eight weeks groups of COPD model in the same time period, and the expression of FIZZ1,TNF- 偽 mRNA and protein in the high dose group was significantly lower than that in the low dose group. The difference was significant (P0.05). Conclusion\ 2. Astragaloside A can reduce airway inflammation and remodeling of COPD and delay the progress of COPD, which may be related to the down-regulation of FIZZ1,TNF- 偽 expression.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R563.9

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