聚乙二醇修飾重組細(xì)胞珠蛋白對小鼠急性肝損傷的保護(hù)作用

李招發(fā)，鄧小英，許佳佳，連文昌

1 華僑大學(xué)分子藥物研究院，福建 泉州 362021

2 華僑大學(xué)分子藥物教育部工程研究中心，福建 泉州 362021

生物技術(shù)與方法

聚乙二醇修飾重組細(xì)胞珠蛋白對小鼠急性肝損傷的保護(hù)作用

李招發(fā)1,2，鄧小英1,2，許佳佳1,2，連文昌1,2

1 華僑大學(xué)分子藥物研究院，福建 泉州 362021

2 華僑大學(xué)分子藥物教育部工程研究中心，福建 泉州 362021

旨在探究聚乙二醇修飾重組細(xì)胞珠蛋白 (PEG modified recombinant cytoglobin，PEG-rCygb) 對小鼠急性肝損傷的保護(hù)作用。采用CCl4誘導(dǎo)KM小鼠急性肝損傷模型，尾靜脈注射PEG-rCygb，收集血清及肝臟組織檢測各項(xiàng)生化指標(biāo)及組織病理學(xué)變化。結(jié)果表明，PEG-rCygb治療組小鼠肝臟系數(shù)減小, 血清中AST﹑ALT水平降低, 肝組織勻漿中MDA含量減少, GSH含量增加，T-SOD、CAT活性升高。肝組織切片HE染色顯示 PEG-rCygb可以緩解肝細(xì)胞脂肪變性, 減少炎癥因子, 減輕肝細(xì)胞損傷。體外細(xì)胞學(xué)實(shí)驗(yàn)表明 rCygb經(jīng)PEG修飾后對H2O2造成的肝星狀細(xì)胞 (HSC) 氧化損傷發(fā)揮的保護(hù)作用增強(qiáng)。研究結(jié)果顯示PEG-rCygb提高了機(jī)體對自由基的清除能力, 對CCl4引起的小鼠急性肝損傷具有保護(hù)作用。

聚乙二醇，重組細(xì)胞珠蛋白，氧化應(yīng)激，急性肝損傷，氧自由基

Abstract:To investigate the protective effect of polyethylene glycol (PEG) modified recombinant cytoglobin(PEG-rCygb) on acute liver damage in mice. The acute liver injury model of KM mice was induced by CCl4and then treated with PEG-rCygb, The liver and blood samples were collected for biochemical and histopathological analysis. The results showed that PEG-rCygb reduced the liver mass index and decreased significantly the levels of alanine amiotransferase (AST) and aspartate transaminase (ALT) in mouse serum. In liver tissues, the content of malondialdehyde(MDA) was decreased, whereas the content of glutathione (GSH) was increased in PEG-rCygb treated group. PEG-rCygb also elevated the activities of total super oxidedismutase (T-SOD) and catalase (CAT) in liver tissues. HE staining of liver tissue slices revealed that PEG-rCygb relieved fatty degeneration of liver, decreased inflammatory factors and reduced liver cell injury. Further in vitro experiments indicated that the protective effects of PEG-rCygb on hepatic stellate cell (HSC)against H2O2were enhanced compared with that of rCygb. All results indicated that the PEG-rCygb promoted oxygen free radical scavenging ability and prevented acute liver injury in KM mice induced by CCl4.

Keywords:PEG, recombinant cytoglobin, anti-oxidative, acute liver damage, oxygen free radical

細(xì)胞珠蛋白 (Cytoglobin，Cygb) 是血紅素球蛋白超家族中的新成員，由Kawada等在大鼠肝星狀細(xì)胞中發(fā)現(xiàn)[1]，是一個(gè)分子量為 21 kDa的胞漿蛋白。在生理狀態(tài)下以單體形式存在，由190個(gè)氨基酸殘基組成，具有傳統(tǒng)的螺旋轉(zhuǎn)角螺旋三明治結(jié)構(gòu)，在人體各組織及發(fā)育的各個(gè)階段分布廣泛[2]，同其他球蛋白家族成員血紅蛋白(Hemoglobin，Hb)、肌紅蛋白 (Myoglobin，Mb)和腦紅蛋白 (Neuroglobin，Ngb) 一樣，能夠與氧可逆結(jié)合并具有高親和力[3]。……