蝦青素對(duì)百草枯致大鼠肺纖維化的干預(yù)作用及機(jī)制
發(fā)布時(shí)間:2018-03-02 11:00
本文關(guān)鍵詞: 百草枯 肺間質(zhì)纖維化 蝦青素 出處:《南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版)》2017年04期 論文類型:期刊論文
【摘要】:目的:觀察蝦青素(astaxanthin,AX)對(duì)百草枯(paraquat,PQ)誘導(dǎo)大鼠肺纖維化的影響,并進(jìn)一步探討肺纖維化可能的發(fā)病機(jī)制。方法:SD大鼠隨機(jī)分為正常對(duì)照組、PQ模型組及蝦青素干預(yù)組。模型組及干預(yù)組大鼠腹腔注射百草枯造模后,干預(yù)組第2天起給予蝦青素灌胃,對(duì)照組及模型組給予相應(yīng)溶劑。分別于給藥后第7、14、28天處死大鼠,測(cè)定大鼠血清中羥脯氨酸(hydroxyproline,HYP)、基質(zhì)金屬蛋白酶(matrix metalloproteinase,MMP)1、MMP2、MMP9和基質(zhì)金屬蛋白酶組織抑制劑(tissue inhibitor of matrix metalloproteinase1,TIMP1)的含量,取固定部位肺組織切片行HE、Masson染色進(jìn)行病理學(xué)觀察,免疫組化法測(cè)定轉(zhuǎn)化生長(zhǎng)因子-β1(TGF-β1)的含量,對(duì)病理圖像進(jìn)行形態(tài)學(xué)測(cè)量分析。結(jié)果:(1)HE染色及Masson染色結(jié)果顯示:干預(yù)組纖維化炎癥程度明顯低于模型組;(2)模型組大鼠中毒后羥脯氨酸較正常組增高(P0.05),蝦青素干預(yù)后,大鼠鼠肺血清羥脯氨酸水平較模型組降低(P0.05);(3)PQ模型組在肺纖維化區(qū)域TGF-β1弱陽(yáng)性表達(dá),蝦青素干預(yù)后,TGF-β1表達(dá)含量下降,第28天最為明顯,差異有統(tǒng)計(jì)學(xué)意義(P0.05);(4)模型組與干預(yù)組MMP1、MMP2、MMP9表達(dá)含量均較正常對(duì)照組升高。MMP1、MMP2、MMP9在PQ中毒后表達(dá)量逐漸升高,第14天達(dá)到高峰后下降,但第28天含量仍高于對(duì)照組。與模型組相比,干預(yù)組MMP2、MMP9含量均有下降,第14、28天顯著,其差異有統(tǒng)計(jì)學(xué)意義(P0.05)。TIMP1在干預(yù)期間與模型組及對(duì)照組無顯著差異。結(jié)論:蝦青素能夠減弱肺纖維化大鼠肺組織病理的膠原沉積、減少肺組織中羥脯氨酸的含量、降低肺血清中MMP2、MMP9的含量,抑制肺組織中TGF-β1的分泌,從而減輕PQ引起的大鼠肺纖維化。
[Abstract]:Objective: To observe the effect of astaxanthin (astaxanthin, AX) on paraquat (paraquat, PQ) induced pulmonary fibrosis in rats, and to further explore the pathogenesis of pulmonary fibrosis. Methods: SD rats were randomly divided into normal control group, PQ model group and astaxanthin intervention group. The model group and intervention group rats by intraperitoneal injection paraquat after modeling, the intervention group from the second day to give intragastric administration of astaxanthin, control group and model group were given corresponding solvent respectively. All rats were killed on day 7,14,28 after administration, the determination of hydroxyproline in serum of rats (hydroxyproline, HYP), matrix metalloproteinases (matrix metalloproteinase, MMP MMP9 and MMP2, 1). Tissue inhibitor of matrix metalloproteinases (tissue inhibitor of matrix metalloproteinase1, TIMP1) the content of fixed parts of the lung tissue sections for HE, Masson staining for pathological observation, immunohistochemical determination of transforming growth factor beta 1 (TGF- beta 1) The content analysis of the pathological images were measured. Results: (1) HE staining and Masson staining showed that the inflammation degree of fibrosis in intervention group was significantly lower than the model group; (2) poisoning model of rats were higher than normal group (P0.05), astaxanthin after intervention decreased serum hydroxyproline levels compared with rat lung the model group (P0.05); (3) PQ in pulmonary fibrosis model group TGF- beta 1 weakly positive expression, astaxanthin intervention, TGF- beta 1 expression decreased. The twenty-eighth day was the most obvious, the difference was statistically significant (P0.05); (4) model group and intervention group MMP1, MMP2, MMP9 expression levels were compared with the normal control group increased.MMP1, MMP2, MMP9 expression in PQ after poisoning was gradually increased, reaching a peak at fourteenth days after twenty-eighth days of decline, but the content is still higher than the control group. Compared with the model group, the intervention group MMP2, MMP9 were decreased significantly after 14,28 days, the difference was statistically significant ( P0.05).TIMP1 during the intervention and the model group and the control group had no significant difference. Conclusion: astaxanthin can decrease pathological collagen deposition in lung tissue of pulmonary fibrosis rats, reduce the content of hydroxyproline in lung tissue, reduce lung MMP2 in serum, the content of MMP9, TGF- beta 1 inhibits the secretion of lung tissue, thereby reducing caused by PQ pulmonary fibrosis in rats.
【作者單位】: 南京醫(yī)科大學(xué)附屬常州第二人民醫(yī)院呼吸科;
【分類號(hào)】:R563
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