多聚鳥嘌呤核苷酸對矽塵致大鼠肺纖維化干預(yù)作用及機(jī)制研究
本文選題:矽肺 切入點(diǎn):多聚鳥嘌呤核苷酸 出處:《中國職業(yè)醫(yī)學(xué)》2017年01期
【摘要】:目的觀察多聚鳥嘌呤核苷酸(Poly G)對染矽塵大鼠肺纖維化的干預(yù)作用,并探討其作用機(jī)制。方法無特定病原體級健康成年雄性SD大鼠隨機(jī)分為對照組、矽肺模型組和4個(gè)干預(yù)組(即干預(yù)1、2、3、4次組),每組5只。除對照組外,其余5組大鼠均以非暴露式氣管插管法一次性予質(zhì)量濃度為50.0 g/L的矽塵混懸液1.0 m L造模,4個(gè)干預(yù)組大鼠分別于造模后第1~21天內(nèi)腹腔注射1、2、3、4次劑量為2.5 mg/kg體質(zhì)量的Poly G。造模后28 d處死大鼠,觀察肺部組織病理學(xué)改變情況,以Ashcroft評分法評估肺纖維化程度,以蛋白免疫印跡法測定肺組織內(nèi)膠原樣結(jié)構(gòu)巨噬細(xì)胞受體(MARCO)、轉(zhuǎn)化生長因子-β1(TGF-β1)、E-鈣黏蛋白(E-cad)、波形蛋白(Vimentin)和α-平滑肌肌動(dòng)蛋白(α-SMA)的蛋白相對表達(dá)水平。結(jié)果矽肺模型組大鼠肺泡腔內(nèi)有大量塵細(xì)胞聚集,肺間質(zhì)內(nèi)出現(xiàn)彌漫性的膠原沉積,說明矽肺造模成功;干預(yù)1次組大鼠肺泡結(jié)構(gòu)基本完整,肺纖維化程度較矽肺模型組明顯減輕。與對照組比較,矽肺模型組大鼠肺組織Ashcroft評分和MARCO、TGF-β1、Vimentin、α-SMA的蛋白相對表達(dá)水平均升高(P0.05),E-cad相對表達(dá)水平下降(P0.05);與矽肺模型組比較,干預(yù)1次組大鼠肺組織的TGF-β1、Vimentin和α-SMA的蛋白相對表達(dá)水平均下降(P0.05),E-cad相對表達(dá)水平升高(P0.05)。Poly G干預(yù)次數(shù)與大鼠肺組織的Ashcroft評分和MARCO、TGF-β1、E-cad、Vimentin、α-SMA的蛋白相對表達(dá)水平之間均無劑量-效應(yīng)關(guān)系。結(jié)論 Poly G可改善矽塵所致的大鼠肺組織炎癥和纖維化,以在造模后第1天進(jìn)行一次性干預(yù)(2.5 mg/kg體質(zhì)量,腹腔注射)效果較好,其機(jī)制可能與低劑量Poly G抑制上皮間質(zhì)轉(zhuǎn)化的進(jìn)程從而減少膠原合成有關(guān)。
[Abstract]:Objective to observe the effect of Poly G on pulmonary fibrosis in silicotic rats. Methods healthy male SD rats with no specific pathogens were randomly divided into control group. Silicosis model group and 4 intervention groups (5 rats in each group, 5 rats in each group, except the control group), The rest of the five groups were treated with unexposed endotracheal intubation for a single dose of 50.0 g / L silica dust suspension 1.0 mL. The rats in the four intervention groups were injected intraperitoneally with 1 2 渭 g / L 1. 5 mg/kg body mass respectively within 21 days after the establishment of the model, and the other 5 groups were given intraperitoneal injection of 2. 5 mg / L silica dust suspension at a dose of 2. 5 g / L respectively within 21 days after the establishment of the model. The rats were killed 28 days after Poly G. The changes of lung histopathology were observed and the degree of pulmonary fibrosis was evaluated by Ashcroft score. The relative expression levels of collagen like macrophage receptor (MARCOG), transforming growth factor- 尾 1 (TGF- 尾 1) E-cadn (vimentin) and 偽 -SMAs in lung tissue were measured by Western blot. Results the results showed that the expression of 偽 -SMAs in silicosis model group was higher than that in control group. In the alveolar cavity of rats, a large number of dust cells gathered, The diffuse collagen deposition in the interstitial tissue of the lung indicated that the silicosis model was successful, the alveolar structure of the rats in the first intervention group was basically intact, the degree of pulmonary fibrosis was significantly reduced than that in the silicosis model group, and compared with the control group, In silicosis model group, the Ashcroft score of lung tissue and the relative expression level of MARCO-TGF- 尾 1 Vimentin, 偽 -SMA protein were increased. The relative expression levels of TGF- 尾 1 Vimentin and 偽 -SMA in the lung tissue of the first intervention group were decreased. The relative expression level of P0.05TGF- 尾 1 E-cadVimentin, 偽 -SMA protein was not dose-effective between the relative expression level of P0.05TGF- 尾 1 E-cadVimentin, 偽 -SMA protein and the Ashcroft score of lung tissue and the relative expression level of 偽 -SMA protein. Conclusion Poly G can improve pulmonary inflammation and fibrosis induced by silica dust in rats. The effect of one-off intervention on the first day after the model was 2. 5 mg/kg (intraperitoneal injection) might be related to the inhibition of the process of epithelial interstitial transformation by low dose Poly G and the reduction of collagen synthesis.
【作者單位】: 華北理工大學(xué)公共衛(wèi)生學(xué)院;新鄉(xiāng)醫(yī)學(xué)院公共衛(wèi)生學(xué)院;
【基金】:國家自然科學(xué)基金(81273017) 河南省科技攻關(guān)項(xiàng)目(162102310491)
【分類號】:R135.2;R563
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