ATRA對(duì)急性肺損傷大鼠肺組織MMP-9表達(dá)的影響
發(fā)布時(shí)間:2018-05-17 02:04
本文選題:全反式維甲酸 + 急性肺損傷; 參考:《重慶醫(yī)科大學(xué)》2012年碩士論文
【摘要】:目的研究脂多糖(Lipopolysaccharide,LPS)所致急性肺損傷大鼠中基質(zhì)金屬蛋白酶-9(Matrix metalloproteinase-9,MMP-9)及相關(guān)炎性指標(biāo)的變化情況,以及全反式維甲酸(All-trans retinonic acid,ARTA)對(duì)其表達(dá)的影響,旨在探討全反式維甲酸在減輕急性肺損傷肺部炎癥的治療作用。 方法將30只SD大鼠隨機(jī)分為3組:生理鹽水對(duì)照組、ALI組及ATRA干預(yù)組。后兩組復(fù)制急性肺損傷模型通過(guò)尾靜脈注射脂多糖(5ml/kg)建立,ALI組在尾靜脈注射脂多糖之前5d,每天以植物油灌胃(0.5ml/kg·次)1次,注射脂多糖后立即經(jīng)腹腔注射植物油(1ml/kg);ATRA干預(yù)組在尾靜脈注射脂多糖之前5d,每天以含有30mg/kg ATRA的植物油灌胃(0.5ml/kg·次)1次,注射脂多糖后立即經(jīng)腹腔注射含5mg/kg ATRA的植物油(1ml/kg);對(duì)照組在整個(gè)實(shí)驗(yàn)過(guò)程中均采用生理鹽水(0.5ml/kg)以同樣的方式進(jìn)行對(duì)照處理。腹腔注射ATRA8h后處死3組大鼠,并測(cè)定每只大鼠動(dòng)脈血樣分壓(PaO2)、支氣管肺泡灌洗液(Bronchial alveolar lavage fluid,BALF)中蛋白含量以及肺組織濕/干比重(Wet/Dry,W/D),顯微鏡下觀察肺組織蘇木精-伊紅(Hematoxylin-eosin,HE)染色情況,并采用RT-PCR、蛋白印跡(westernblot,WB)及免疫組化檢測(cè)肺組織中MMP-9基因mRNA及蛋白的表達(dá)。 結(jié)果ALI組大鼠肺組織炎性細(xì)胞與對(duì)照組比較明顯增多,,動(dòng)脈PaO2明顯下降(P0.05),W/D、BALF中蛋白含量、肺組織中MMP-9基因mRNA及蛋白含量均明顯升高(P0.05);與ALI組相比,干預(yù)組模型肺組織炎癥反應(yīng)明顯改善,W/D、BALF中蛋白含量、肺組織中MMP-9基因mRNA及蛋白表達(dá)水平明顯下降(P0.05或P0.01),其動(dòng)脈PaO2亦有所改善(P0.05)。 結(jié)論MMP-9可能參與ALI的炎性過(guò)程,ATRA對(duì)脂多糖所致ALI具有治療作用,其機(jī)制可能是通過(guò)降低MMP-9的表達(dá)所實(shí)現(xiàn)的。
[Abstract]:Objective to study the changes of matrix metalloproteinase-9 (MMP-9) and its related inflammatory markers in rats with acute lung injury induced by lipopolysaccharide (LPS) and the effect of all-trans retinonic acidar on the expression of matrix metalloproteinase-9 (MMP-9) in rats with acute lung injury induced by lipopolysaccharide (LPS). To investigate the therapeutic effect of all-trans retinoic acid (ATRA) on pulmonary inflammation in acute lung injury. Methods Thirty SD rats were randomly divided into three groups: saline control group and ATRA intervention group. Acute lung injury model was established in the latter two groups by injecting lipopolysaccharide (LPS) 5 ml / kg into the tail vein. In the Ali group, 0.5 ml / kg of vegetable oil was injected into the stomach 5 days before lipopolysaccharide was injected into the tail vein. Immediately after lipopolysaccharide was injected intraperitoneally, 1 ml / kg of vegetable oil was injected intraperitoneally in the intervention group, 5 days before injection of lipopolysaccharide into caudal vein, 0.5 ml / kg of vegetable oil containing 30mg/kg ATRA was injected into the stomach of the intervention group once a day. Immediately after lipopolysaccharide injection, 1 ml / kg 5mg/kg ATRA containing vegetable oil was injected intraperitoneally, while the control group was treated in the same way with normal saline 0.5 ml / kg. Three groups of rats were killed after intraperitoneal injection of ATRA8h. The protein content of Pao _ 2 and bronchoalveolar alveolar lavage were measured in each rat, and the wet / dry specific gravity of lung tissue (Wet / Dryster / WDV) was measured. The staining of hematoxylin-eosinine (HEH) in lung tissue was observed under microscope. The expression of MMP-9 gene mRNA and protein in lung tissue was detected by RT-PCR (Western blotl) and immunohistochemistry. Results compared with the control group, the inflammatory cells of lung tissue in ALI group increased significantly, and the content of PaO2 in arterial PaO2 decreased significantly, while the protein content of MMP-9 gene mRNA and protein in lung tissue increased significantly, compared with that of ALI group, compared with ALI group, the content of MMP-9 gene mRNA and protein in lung tissue of ALI group was significantly higher than that of ALI group. In the intervention group, the inflammatory reaction of lung tissue significantly improved the protein content in the lung tissue, and the expression of MMP-9 gene mRNA and protein in the lung tissue decreased significantly (P0.05 or P0.01), and the arterial PaO2 also improved P0.05. Conclusion MMP-9 may be involved in the inflammatory process of ALI. ATRA may be involved in the treatment of ALI induced by lipopolysaccharide, and its mechanism may be by decreasing the expression of MMP-9.
【學(xué)位授予單位】:重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類(lèi)號(hào)】:R563.8
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 ;Induction of acute hepatic injury by endotoxin in mice[J];Hepatobiliary & Pancreatic Diseases International;2002年04期
2 孫中吉,盧青;急性呼吸窘迫綜合征發(fā)病中的細(xì)胞因子和炎性介質(zhì)[J];中國(guó)危重病急救醫(yī)學(xué);2003年03期
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