152中國(guó)生化藥物雜志Chinese Joumal of Biochemical Pharnaceutics 2007年第28卷第3期聚乙二醇化重組復(fù)合干擾素對(duì)小鼠免疫功能的影響研究趙媛',趙偉',姚文兵',趙艷玲，高向東'(1.中國(guó)藥科大學(xué)生命科學(xué)與技術(shù)學(xué)院，江蘇南京210009; 2.解放軍第302醫(yī)院，北京100039)摘要:目的研究聚乙二醇化重組復(fù)合干擾素(PE-IFNcom)對(duì)小鼠免疫功能的影響。方法以重組復(fù)合干擾素(IFNcon,商品 名:干復(fù)津)為對(duì)照,分別采用雞紅細(xì)胞吞噬法和四甲基偶氮唑鹽(MTT)比色法測(cè)定巨嗜細(xì)胞吞噬功能和淋巴細(xì)胞增殖作用,以3H-TdR摻入法測(cè)定刀豆蛋白A(Con A)誘導(dǎo)的淋巴細(xì)胞增殖活動(dòng)。結(jié)果PEG IFNeon能提高小鼠腹腔巨噬細(xì)胞吞噬功能,顯著改善環(huán)磷酰胺所致的小鼠淋巴細(xì)胞功能降低作用,在50~ 150 rg/mL劑量范圍內(nèi)亦能增強(qiáng)小鼠Con A誘導(dǎo)的淋巴細(xì)胞增殖反應(yīng)。結(jié)論P(yáng)EC-IFNeon 可顯著增強(qiáng)小鼠免疫功能。關(guān)鍵詞:聚乙二醇化復(fù)合干擾素;復(fù)合干擾素;巨嗜細(xì)胞吞噬;淋巴細(xì)胞增殖;免疫功能中圖分類號(hào):R978.7; R965文獻(xiàn)標(biāo)識(shí)碼:A文章編號(hào):1005-1678(2007 )03-0152-03Study on the effect of pegylatied recombinant consensus interferon onimmuno-function in miceZHAO Yuan' , ZHAO Wei' ，YAO Wen-bing' ，ZHAO Yan- ling2 , CAO Xiang dong'(1. School of Life Science and Technology, China Pharmaceuical University， Nanjing 210009，China;2. No . 302 Hospital of Chinese PLA, Beijing 100039, China )Abstract: Purpose To study the efcts of pegylated recombinant consensus interferon( PEG-IFNcon) onthe immuno-function of rats . Methods The tests were carried out with the PEG- IFNcon by contrast of recombi-nant consensus interferon( Infergen , IFNcon) . The chicken red blood cells( CRBC) phagocytosis assay and theMTT assay were used to evaluate the phagocytic ability of peritoneal macrophage( Mφ )and lymphocyte prolifer-ation respectively. Proliferation of splenocytes in response to ConA was detected by 3 H-TdR labeling.Results PEG- IFNcon significantly increases the phagocytic of peritoneal macrophage( Mq) , remarkably revers-es, the immunological inhibition caused by cyclophosphamide and assists the proliferation of lymphocyte in-duced by ConA at the dose of 50- 150 ug/ mL. Conclusion PEC IFNcon could significantly stimulate the immu-nity function in mice.Key words:pegylated consensus interferon; consensus interferon; the phagocytic ability of M中; lympho-cyte proliferation; immuno-function20世紀(jì)90年代以來(lái)，干擾素聚乙二醇化技術(shù)毒作用通過(guò)抑制病毒復(fù)制及廣泛的免疫調(diào)節(jié)雙重模發(fā)展迅速,并已成功應(yīng)用于臨床。聚乙二醇化干擾.式對(duì)病毒進(jìn)行抑制,其免疫調(diào)節(jié)功能通過(guò)包括激活素(PEG-IFNcon)理化性質(zhì)及藥動(dòng)學(xué)性質(zhì)與未修飾干T 輔助細(xì)胞;激活抗原提呈細(xì)胞等多種途徑進(jìn)擾素相比均有顯著變化叫。與目前臨床常用的乙肝行(23。 本文以相對(duì)分子質(zhì)量(M,)為40 000的支鏈治療藥物核苷和核苷酸類似物抗病毒單---作用模式型PEG-IFNcon和未經(jīng)修飾的重組復(fù)合干擾素(IFN-抑制病毒DNA逆轉(zhuǎn)錄不同,a干擾素( IFN-a)的抗病con,商品名:干復(fù)津)為研究對(duì)象,觀察對(duì)PEG-IFN-col1中國(guó)煤化工收稿日期: 2006-05-15; 修回日期: 2006-06-28THC NM !!藥科大學(xué)生命科學(xué)基金項(xiàng)目:“十五*863計(jì)劃(No. 20422380作者簡(jiǎn)介:趙媛(1981-),女,北京人,在讀碩士研究生，主要從事與技術(shù)學(xué)院,批號(hào):050201;IFNcon注射液(商品名:生物新藥開(kāi)發(fā)研究;姚文兵,通信作者,教授,博士生導(dǎo)師,Tel; 025-干復(fù)津),日本山之內(nèi)制藥株式會(huì)社,批號(hào):040703;83271225, E-mail: wbyao @ cpu. edu. en。谷氨酸丙酮酸轉(zhuǎn)氨酶(GPT)、谷氨酸草酰乙酸轉(zhuǎn)氨中國(guó)生化藥物雜志Chinese Joumal of Biochemical Pharmaceutics 2007年第28卷第3期153酶(GOT)測(cè)定試劑盒,北京北化康泰臨床試劑有限數(shù)/巨噬細(xì)胞總數(shù))x 100%(1)公司;環(huán)磷酰胺(Cy)粉針劑,江蘇恒瑞醫(yī)藥股份有限吞噬指數(shù)=被吞噬雞紅細(xì)胞總數(shù)/巨噬細(xì)胞公司,批號(hào):01060821;植物血凝素(PHA),Sigma公總數(shù)司,批號(hào):L8754。2.4 PEG-IFNcon 對(duì)Cy導(dǎo)致的免疫低下小鼠腹腔巨二氧化碳孵箱,Shel-Lab公司;培養(yǎng)瓶,Tunclon噬細(xì)胞吞噬功能的影響公司;培養(yǎng)板96孔板, Corming公司。實(shí)驗(yàn)設(shè)正常對(duì)照組、Cy模型組、Cy+IFNcon組、BALB/c小鼠,體重18~22 g,雌雄各半,中國(guó)生Cy+ PEG-IFNcon組。每組10只，腹腔注射給予小鼠物制品檢定所動(dòng)物中心,動(dòng)物合格證號(hào):SCXK11-00-Cy 15 puy/kg,1次/d,Cy連續(xù)處理4d后皮下注射給0010。藥,每次0.4 mL/只,Cy + IFNcon 組1次/d,Cy +2方法PEG-IFNcon組1次/2d。給藥第6天處死動(dòng)物取2.1 PEG-IFNcon體外對(duì)正常小鼠淋巴細(xì)胞增殖反樣。取樣及測(cè)定方法同2.3項(xiàng)。應(yīng)的影響2.5數(shù)據(jù)分析取健康成年雌性小鼠脾臟,制備單細(xì)胞懸液,以試驗(yàn)數(shù)據(jù)以(無(wú)士s)表示,以t檢驗(yàn)法計(jì)算各組20%小牛血清的RPMI 1640液稀釋細(xì)胞至5x 106/間數(shù)據(jù)差別的統(tǒng)計(jì)學(xué)意義,P<0.05差異顯著,P0.05);各組心、對(duì)ACE有抑制作用,但在體內(nèi)不能發(fā)揮降壓作用，腦、腎等臟器ACE活性比較無(wú)顯著性差異其原因主要是多肽被體內(nèi)消化酶(消化系統(tǒng)等)降解(P>0.05)。或不能被吸收[7]。本研究表明玉米降血壓肽能明顯2.4玉米降血壓肽對(duì) SHR血漿AngII 的影響抑制體內(nèi)外ACE活性,而且對(duì)不同部位的ACE抑制連續(xù)給藥12周后,對(duì)照組、卡托普利組及玉米作用不同,其原因尚需通過(guò)進(jìn)一步的藥物吸收及代降血壓肽低、中、高劑量組SHR血漿中AngII濃度分謝動(dòng)力學(xué)研究來(lái)闡明。別為:(1 278土141),(567 士75),(598土63),(764土參考文獻(xiàn):26),(965土61)pg/mL(n=8)。可見(jiàn),玉米降血壓肽[1]趙海珍,陸北新,劉戰(zhàn)民.天然食品米源的血管緊張素轉(zhuǎn)換酶抑各劑量組和卡托普利組SHR血漿AngI濃度顯著低制肽的研究進(jìn)展[J].中國(guó)生化藥物雜志,00.25(5);315-317.[2] Yamanoto N. 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