本文選題：腸道菌群失衡　切入點(diǎn)：糞菌移植　出處：《藥學(xué)學(xué)報(bào)》2017年01期

【摘要】：腸道細(xì)胞色素P450 3A(cytochrome P450 3A,CYP3A)和P-糖蛋白(P-glycoprotein,P-gp)是腸屏障的重要組成部分。炎癥性腸病中腸CYP3A和P-gp下調(diào)伴隨腸道菌群紊亂。但兩者是否關(guān)聯(lián)?機(jī)制如何?尚不清楚。本研究采用5%葡聚糖硫酸鈉誘導(dǎo)大鼠潰瘍性結(jié)腸炎(ulcerative colitis,UC),并對(duì)正常動(dòng)物分別灌胃正常及UC動(dòng)物糞便,發(fā)現(xiàn)糞便移植改變了受體動(dòng)物腸道菌組成,而移植UC糞便組腸CYP3A2和P-gp mRNA的表達(dá)顯著下調(diào)。外膜囊泡(outer-membrane vesicles,OMVs)是革蘭陰性菌產(chǎn)生、進(jìn)行群體行為及與環(huán)境通信的關(guān)鍵結(jié)構(gòu)。不同處理組的OMVs均能下調(diào)人結(jié)腸腺癌細(xì)胞Caco-2中CYP3A4和P-gp的mRNA表達(dá),而UC組以及UC糞便處理組的OMVs的抑制作用更強(qiáng),且相對(duì)分子質(zhì)量3~5萬(wàn)的OMVs組分的作用更顯著。細(xì)胞經(jīng)toll樣受體4(toll like receptor 4,TLR4)抑制劑瑞沙托維處理或轉(zhuǎn)染TLR4 si RNA能夠阻斷OMVs對(duì)CYP3A4和P-gp的下調(diào)。本研究證實(shí),UC腸道菌部分通過(guò)分泌OMVs活化TLR4受體通路下調(diào)腸道CYP3A和P-gp表達(dá)。
[Abstract]:Intestinal cytochrome P450 3A(cytochrome P450 3A (CYP3A) and P-glycoprotein P-glycoprotein (P-gp) are important components of intestinal barrier. The down-regulation of CYP3A and P-gp in the midgut of inflammatory bowel disease is associated with intestinal flora disorder. What about the mechanism? In this study, 5% sodium dextran sulfate was used to induce ulcerative colitis in rats, and normal and UC faeces were perfused to normal and UC animal faeces respectively. It was found that fecal transplantation changed the composition of intestinal bacteria in recipient animals. However, the expression of CYP3A2 and P-gp mRNA was down-regulated in UC feces transplantation group. Outer membrane vesiclesnus OMVswere produced by Gram-negative bacteria. OMVs of different treatment groups could down-regulate the mRNA expression of CYP3A4 and P-gp in Caco-2 of human colon adenocarcinoma cells, but OMVs in UC group and UC fecal treatment group had stronger inhibitory effect. The effect of OMVs components with relative molecular weight of 350-50 000 was more significant. Cells treated with toll like receptor 4(toll like receptor 4tLR4) or transfected with TLR4 si RNA could block the down-regulation of CYP3A4 and P-gp by OMVs. The expression of CYP3A and P-gp was down-regulated by secreting OMVs activated TLR4 receptor pathway.
【作者單位】： 澳門(mén)大學(xué)中華醫(yī)藥研究院中藥質(zhì)量研究國(guó)家重點(diǎn)實(shí)驗(yàn)室(澳門(mén)大學(xué));珠海澳大科技研究院;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(81473281) 973基金資助項(xiàng)目(2009CB522707) 澳門(mén)大學(xué)基金資助項(xiàng)目(MYRG2015-00220)
【分類(lèi)號(hào)】：R574.62

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