本文選題：肝損傷 + microRNAs　； 參考：《四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2017年03期

【摘要】：目的觀察四氯化碳(CCl_4)誘導(dǎo)的大鼠急性肝損傷模型和對(duì)乙酰氨基酚(APAP)誘導(dǎo)的小鼠急性肝損傷模型血清中microRNAs(miR-122、miR-451、miR-92a、miR-192)的絕對(duì)定量隨時(shí)間的變化情況,并分析血清中microRNAs絕對(duì)定量與對(duì)乙酰氨基酚誘導(dǎo)的小鼠急性肝損傷組織病理評(píng)分之間的相關(guān)性。方法建立CCl_4(1.5mL/kg)誘導(dǎo)的大鼠急性肝損傷模型和APAP(160mg/kg)誘導(dǎo)的小鼠急性肝損傷模型,收集建模過程中各時(shí)間點(diǎn)的血清,通過MiRbay~(TM) SV miRNA檢測(cè)試劑盒對(duì)血清中microRNAs的含量進(jìn)行絕對(duì)定量,探究血清中microRNAs的變化情況。同時(shí)收集APAP誘導(dǎo)的小鼠急性肝損傷模型中各時(shí)間點(diǎn)的肝損傷組織,進(jìn)行組織病理染色、組織病理評(píng)分;隨后對(duì)小鼠血清中microRNAs的絕對(duì)定量與肝損傷組織病理評(píng)分進(jìn)行相關(guān)性分析。結(jié)果在兩種急性肝損傷模型中,均發(fā)現(xiàn)血清中miR-122和miR-192的絕對(duì)定量在肝損傷8h或2h就出現(xiàn)明顯的升高,在24h左右維持在最高的水平,72h逐漸下降至正常水平。miR-92a在CCl_4誘導(dǎo)的大鼠急性肝損傷模型中,出現(xiàn)波動(dòng)性的變化,無明顯的變化規(guī)律,miR-451則出現(xiàn)了輕微下降的趨勢(shì)。miR-92a和miR-451在APAP誘導(dǎo)的小鼠肝損傷進(jìn)展中,均有逐漸下降的趨勢(shì),在48h到達(dá)最低點(diǎn),隨后開始恢復(fù)。相關(guān)性分析發(fā)現(xiàn),小鼠血清中miR-122和miR-192的絕對(duì)定量與APAP誘導(dǎo)的小鼠肝損傷組織病理評(píng)分(DILI-PSS)呈現(xiàn)良好的正相關(guān)(分別為r=0.741 3,P0.05;r=0.788 3,P0.01)。結(jié)論血清中microR-122和microR-192的絕對(duì)定量在大鼠或小鼠急性肝損傷后24h左右達(dá)峰,72h降低,并且與APAP誘導(dǎo)的小鼠急性肝損傷組織病理評(píng)分具有良好的相關(guān)性。
[Abstract]:Objective to observe the changes of serum microRNAsmiR-121 miR-451miR-92a miR-1922) in the acute liver injury model of rats induced by CClSIV) and the acute liver injury model induced by paracetamol APAP1), and to observe the changes of the absolute quantity of microRNAsmiR-121 miR-451 miR-92a miR-1922 in serum of rats with acute liver injury induced by acetaminophen (APAP). The relationship between the absolute quantity of microRNAs in serum and the pathological score of acute liver injury in mice induced by paracetamol was analyzed. Methods the acute liver injury model of rats induced by CCl4L / kg and acute liver injury model of mice induced by APAPN 160 mg / kg were established. Serum samples were collected at different time points during the modeling process. The levels of microRNAs in serum were measured by SV miRNA assay kit. To explore the changes of microRNAs in serum. At the same time, the tissue of acute liver injury in mice induced by APAP was collected at different time points, and then the relationship between the absolute quantity of microRNAs in serum and the pathological score of liver injury was analyzed. Results in both acute liver injury models, the absolute quantification of miR-122 and miR-192 in serum was significantly increased at 8h or 2h after liver injury. At the highest level at about 24 h, it gradually decreased to the normal level. MiR-92a showed the change of volatility in CClS4 induced acute liver injury model in rats. Without obvious change, miR-451 showed a slight downward trend. MiR-92a and miR-451 showed a decreasing trend in the progression of liver injury induced by APAP, reached the lowest point at 48h, and then recovered. The correlation analysis showed that the absolute quantification of miR-122 and miR-192 in serum was positively correlated with the pathological score of liver injury in mice induced by APAP (r = 0.741 3, P 0.05 0. 788 3 P 0.01). Conclusion the absolute quantification of microR-122 and microR-192 in serum decreased at about 24 hours after acute liver injury in rats or mice, and had a good correlation with the pathological score of acute liver injury induced by APAP in mice.
【作者單位】： 四川大學(xué)生命科學(xué)學(xué)院;四川大學(xué)實(shí)驗(yàn)動(dòng)物中心;
【分類號(hào)】：R-332;R575

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