本文關(guān)鍵詞： 百草枯 肺損傷 細胞凋亡 內(nèi)質(zhì)網(wǎng)應(yīng)激 沙苑子總黃酮　出處：《醫(yī)學(xué)研究生學(xué)報》2014年08期 　論文類型：期刊論文

【摘要】：目的肺組織是百草枯中毒后主要損傷的靶器官,但其具體機制目前尚未完全清楚。內(nèi)質(zhì)網(wǎng)應(yīng)激(endoplasmic reticulum stress,ERS)與中毒相關(guān)性疾病密切相關(guān),但其與百草枯中毒后肺損傷的關(guān)系鮮見報道。文中探討ERS誘導(dǎo)的細胞凋亡在大鼠百草枯中毒后急性肺損傷(acute lung injury,ALI)中的作用及觀察中藥沙苑子黃酮(total flavonoids from astragalus complanatus,FAC)對其影響。方法 30只Spragne-Dawley(SD)大鼠按隨機數(shù)字表法分為對照組、肺損傷模型組(ALI組)和沙苑子黃酮處理組(ALI+FAC組)。采用生物化學(xué)法檢測肺組織超氧化物歧化酶(SOD)、過氧化氫酶(CAT)和丙二醛(MDA)含量;采用原位末端標記(TUNEL)法觀察肺組織凋亡情況;采用Western blot及RT-PCR檢測ALI后CCAAT增強子結(jié)合蛋白(C/EBP)同源蛋白(C/EBP homologous protein,CHOP)、活化的轉(zhuǎn)錄因子4(activating transcription factor 4,ATF4)和X-盒結(jié)合蛋白-1(X-box binding protein 1,XBP1)基因表達的改變;HE染色觀察肺組織病理變化。結(jié)果與對照組相比,ALI組的肺組織中MDA水平明顯升高[(3.26±0.24)vs(5.04±0.36),P0.01],SOD和CAT活性明顯降低,分別為[(300.26±35.69)vs(187.21±25.66)]、[(5.78±1.28)vs(2.15±1.12),P0.01],細胞凋亡數(shù)增多,CHOP蛋白表達上調(diào)[(0.74±0.20)vs(0.23±0.07),P0.01],XBP-1、ATF4和CHOP mRNA表達水平明顯上調(diào)。而沙苑子黃酮作用后,肺組織MDA含量減少[(5.04±0.36)vs(3.99±0.27),P0.01],SOD和CAT活性增加,細胞凋亡明顯減少,CHOP蛋白表達下調(diào)[(0.74±0.20)vs(0.42±0.11),P0.01],ATF4、XBP1和CHOP基因表達下調(diào)。結(jié)論內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)的細胞凋亡參與百草枯中毒后肺損傷過程,沙苑子黃酮對百草枯中毒后肺組織保護作用與其減輕ERS誘導(dǎo)的細胞凋亡有關(guān)。
[Abstract]:Objective Pulmonary tissue is the main target organ after paraquat poisoning. However, the specific mechanism of endoplasmic reticulum stress (ER) is not completely clear. Endoplasmic reticulum stress (ER) is closely related to poisoning related diseases. However, the relationship between ERS and lung injury after paraquat poisoning was rarely reported. The aim of this study was to investigate the role of ERS induced apoptosis in acute lung injury induced by paraquat poisoning in rats. The role and observation of total flavonoids from astragalus complanatus in Astragalus complanatus L. Methods Thirty Spragne-Dawley SD rats were randomly divided into control group. Lung injury model group (Ali group) and Astragalus complanatus flavonoids treatment group (Ali FAC group). The lung tissue superoxide dismutase (SOD) was detected by biochemical method. Catalase catalase (CAT) and malondialdehyde (MDA) content; Tunel was used to observe the apoptosis of lung tissue. Western blot and RT-PCR were used to detect CCAAT enhancer binding protein C / EBP homologous protein (. C/EBP homologous protein. Chopo, an activated transcription factor 4, activates transcription factor 4. ATF4) and X-box binding protein 1 (XBP1) gene expression; The pathological changes of lung tissue were observed by HE staining. Results compared with the control group, the level of MDA in lung tissue of Ali group was significantly higher than that of control group. [The activities of sod and CAT were significantly decreased (5.04 鹵0.36, P0.01), respectively (P < 0.05). [300.26 鹵35.69 vs 187.21 鹵25.66). [The number of apoptosis increased and the expression of chop protein was up-regulated. [XBP-1 was found in 0.74 鹵0.20 鹵0.20 鹵0.23 鹵0.07 (P0.01). The expression of ATF4 and CHOP mRNA was upregulated obviously, while the content of MDA in lung tissue decreased after flavonoids of Astragalus complanatus were treated. [The activities of sod and CAT increased, and apoptosis decreased significantly. The expression of chop protein was down-regulated. [ATF4 was found in 0.74 鹵0.20 鹵0.20 鹵0.42 鹵0.11 (P0.01). Conclusion the apoptosis induced by endoplasmic reticulum stress is involved in the lung injury after paraquat poisoning. The protective effect of flavonoids from Astragalus complanatus on the lung tissue after paraquat poisoning was related to the reduction of apoptosis induced by ERS.
【作者單位】： 重慶市巴南區(qū)人民醫(yī)院ICU;
【基金】：重慶市衛(wèi)生局醫(yī)學(xué)科研計劃項目(2012-2-419)
【分類號】：R563.8
【正文快照】： 0引言作為農(nóng)業(yè)生產(chǎn)中常用的除草劑,百草枯自問世以來中毒事件屢有發(fā)生。肺是百草枯作用于機體最主要的靶器官,肺損傷是百草枯中毒后最常見的致死原因。目前認為百草枯中毒后氧化應(yīng)激是肺損傷的主要機制之一,而內(nèi)質(zhì)網(wǎng)對氧化應(yīng)激非常敏感,當(dāng)其穩(wěn)態(tài)被打亂后將導(dǎo)致內(nèi)質(zhì)網(wǎng)應(yīng)激(endo

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