血栓病治疗药物-纤溶酶的生物来源
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摘要
血栓病的干预方式包括抗血小板凝集、抗凝血和溶栓,对应临床应用的分别是抗血小板、抗凝血酶和纤溶酶溶栓药物;纤溶酶是主要的溶栓类药物,主要用于血栓发病后的治疗。纤溶酶种类多来自于生物体,更多来自于微生物的次级代谢。本文从作用方式、安全性和市场开发等方面总结了国内外纤溶酶的类别、研究现状和发展趋势,并对不同产纤溶酶的微生物菌株类别进行了总结,对不同来源的纤溶酶基因和氨基酸序列等信息进行了比较,发现不同物种的纤溶酶基因虽然有差异,但主要是丝氨酸蛋白酶类,氨基酸序列一致性比较高,说明丝氨酸蛋白酶活性功能区域是相对保守的。
For thrombus, the medical interventions consist of antiplatelet agglutination, antiaggregation, and thrombolysis. The corresponding drugs are antiplatelet, antithrombin, and fibrinolytic enzyme. As the main medical drug for diseased thrombus, most of fibrinolytic enzyme comes from organisms such as secondary metabolism of microbial. This paper discusses the classification, research status, and developing trends of fibrinolytic enzyme at home and abroad from the perspectives of type of action, safety, and tap potential. The strains of microorganism producing fibrinolytic enzyme are summarized. The comparison results show that the fibrinolytic enzyme gene sequence was different for different species, but the expression of protein-amino acid sequence was more consistent. It also proved that protein functional region of the serine protease is conservative.
For thrombus, the medical interventions consist of antiplatelet agglutination, antiaggregation, and thrombolysis. The corresponding drugs are antiplatelet, antithrombin, and fibrinolytic enzyme. As the main medical drug for diseased thrombus, most of fibrinolytic enzyme comes from organisms such as secondary metabolism of microbial. This paper discusses the classification, research status, and developing trends of fibrinolytic enzyme at home and abroad from the perspectives of type of action, safety, and tap potential. The strains of microorganism producing fibrinolytic enzyme are summarized. The comparison results show that the fibrinolytic enzyme gene sequence was different for different species, but the expression of protein-amino acid sequence was more consistent. It also proved that protein functional region of the serine protease is conservative.
引文
[1]庞兴学,王显.血栓形成的过程与机制研究进展[J].医学综述,2011,17(11):1613-1616.DOI:10.3969/j.issn.1006-2084.2011.11.005.PANG Xingxue,WANG Xian.Research progress in thrombosis and its mechanism[J].Medical Recapitulate,2011,17(11):1613-1616.DOI:10.3969/j.issn.1006-2084.2011.11.005.
[2]吕翠平,董小黎.肺血栓栓塞的治疗进展[J].临床荟萃,2005,20(14):836-838.DOI:10.3969/j.issn.1004-583X.2005.14.039.Lü Cuiping,DONG Xiaoli.Treatment progress in pulmonary thromboembolism[J].Clinical Focus,2005,20(14):836-838.DOI:10.3969/j.issn.1004-583X.2005.14.039.
[3]LOSI M A,GOLINO P,BETOCCHI S,et al.Massive chronic atrial thrombosis[J].International Journal of Cardiology,2003,90(2):323-324.DOI:10.1016/S0167-5273(02)00508-9.
[4]奉涛.溶栓药物的临床应用及其进展[J].临床合理用药杂志,2011,04(17):145-146.DOI:10.3969/j.issn.1674-3296.2011.17.132.FENG Tao.Advancement and clinical application on thrombolytic[J].Chinese Journal of Clinical Rational Drug Use,2011,04(17):145-146.DOI:10.3969/j.issn.1674-3296.2011.17.132.
[5]NELSON H,SARGENT D J,WIEAND H S,et al.A comparison of laparoscopically assisted and open colectomy for colon cancer[J].New England Journal of Medicine,2004,350(20):2050-2059.DOI:10.1056/NEJMoa032651.
[6]SUMNER-SMITH G.The safety and tolerability of lumbrokinase DLBS1033 in healthy adult subjects[J].Drug Research,2016,66(06):293-299.DOI:10.1055/s-0035-1569406.
[7]梁鹏宇,潘霞,任宇豪.溶栓酶的研究进展[J].广西科学,2017,24(1):77-82.DOI:10.13656/j.cnki.gxkx.20170116.002.LIANG Pengyu,PAN Xia,REN Yuhao.Research progress of thrombolytic enzymes[J].Guangxi Science,2017,24(1):77-82.DOI:10.13656/j.cnki.gxkx.20170116.002.
[8]高春杰,张爱香,陈轶暖.蛇毒酶(抗凝溶栓)制剂的应用研究[J].中国医药指南,2010,08(19):235-236.DOI:10.3969/j.issn.1671-8194.2010.19.079.GAO Chunjie,ZHANG Aixiang,CHEN Yinuan.Application of snake venom enzyme (anticoagulant thrombolytic) preparation[J].Guide of China Medicine,2010,08(19):235-236.DOI:10.3969/j.issn.1671-8194.2010.19.079.
[9]曹郁.蛇毒纤溶酶原激活剂TSV-PA在昆虫细胞中的表达[J].生物工程学报,2001,17(5):506-509.DOI:10.3321/j.issn:1000-3061.2001.05.007.CAO Yu.Expression of a snake venom plasminogen activator TSV-PA in insect cells[J].Chinese Journal of Biotechnology,2001,17(5):506-509.DOI:10.3321/j.issn:1000-3061.2001.05.007.
[10]GARDELL S J,DUONG L T,DIEHL R E,et al.Isolation,characterization,and cDNA cloning of a vampire bat salivary plasminogen activator[J].Journal of Biological Chemistry,1989,264(30):17947.DOI:10.1016/S0005-2728(89)80013-1.
[11]MA D,MIZURINI D M,ASSUMPCAO T C F,et al.Desmolaris,a novel factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in vivo[J].Blood,2013,122(25):4094-4106.DOI:10.1182/blood-2013-08-517474.
[12]刘堰,苏畅,宋小双,等.表达食血蝙蝠唾液纤溶酶原激活剂的毕赤酵母菌株的构建[J].生物工程学报,2009,25(4):566-574.DOI:10.3321/j.issn:1000-3061.2009.04.015.LIU Yan,SU Chang,SONG Xiaoshuang,et al.Construction of pichia pastoris strain expressing salivary plasminogen activator from vampire bat (Desmodus rotundus)[J].Chinese Journal of Biotechnology,2009,25(4):566-574.DOI:10.3321/j.issn:1000-3061.2009.04.015.
[13]HILDEBRANDT J P,LEMKE S.Small bite,large impact-saliva and salivary molecules in the medicinal leech,Hirudo medicinalis[J].Naturwissenschaften,2011,98(12):995-1008.DOI:10.1016/j.radonc.2005.10.002.
[14]徐文杰,谭树华.乳酸菌表达的重组水蛭素的壳聚糖微粒的口服药效学研究[J].药物生物技术,2014(6):547-549.DOI:10.19526/j.cnki.1005-8915.2014.06.013.XU Wenjie,TAN Shuhua.Oral pharmacodynamics of chitosan particles expressed by lactobacillus recombinant hirudin[J].Pharmaceutical Biotechnology,2014(6):547-549.DOI:10.19526/j.cnki.1005-8915.2014.06.013.
[15]丁文惠,高亢.基因重组链激酶静脉溶栓治疗急性心肌梗塞临床研究[J].中国临床药理学杂志,2000,16(4):259-261.DOI:10.3969/j.issn.1001-6821.2000.04.005.DING Wenhui,GAO Kang.Intravenous thrombolysis in patients with acute myocardial infarction-comparison of the efficacy of gene recombined streptokinase[J].The Chinese Journal of Clinical Pharmacology,2000,16(4):259-261.DOI:10.3969/j.issn.1001-6821.2000.04.005.
[16]熊晓辉,梁剑光,熊强.纳豆激酶液体发酵条件的优化[J].食品与发酵工业,2004,30(1):62-66.DOI:10.3321/j.issn:0253-990X.2004.01.016.XIONG Xiaohui,LIANG Jianguang,XIONG Qiang.Optimization of Nattokinase production using liquid fermentation[J].Food and Fermentation Industries,2004,30(1):62-66.DOI:10.3321/j.issn:0253-990X.2004.01.016.
[17]董超,李楠,程辉彩,等.纳豆激酶发酵条件的优化[J].食品科学,2009,30(1):151-154.DOI:10.3321/j.issn:1002-6630.2009.01.036.DONG Chao,LI Nan,CHENG Huicai,et al.Optimization of fermentation conditions for production of Nattokinase[J].Food Science,2009,30(1):151-154.DOI:10.3321/j.issn:1002-6630.2009.01.036.
[18]韩慧明,李咏梅.纳豆激酶基因在大肠杆菌中的表达及活性分析[J].中国生物工程杂志,2014,34(10):49-54.DOI:10.13523/j.cb.20141008.HAN Huiming,LI Yongmei.Secretory expression of Nattokinase from Bacillus natto in Escherichia coli[J].China Biotechnology,2014,34(10):49-54.DOI:10.13523/j.cb.20141008.
[19]CHITTE R R,DEY S.Potent fibrinolytic enzyme from a thermophilic Streptomyces megasporus strain SD5[J].Letters in Applied Microbiology,2010,31(6):405-410.DOI:10.1046/j.1365-2672.2000.00831.x.
[20]CHITTE R R,DEY S.Production of a fibrinolytic enzyme by thermophilic Streptomyces species[J].World Journal of Microbiology and Biotechnology,2002,18(4):289-294.DOI:10.1023/a:1015252607118.
[21]MANDER P,CHO S S,SIMKHADA J R,et al.A low molecular weight chymotrypsin-like novel fibrinolytic enzyme from Streptomyces sp.CS624[J].Process Biochemistry,2011,46(7):1449-1455.DOI:10.1016/j.procbio.2011.03.016.
[22]SIMKHADA J R,MANDER P,CHO S S,et al.A novel fibrinolytic protease from Streptomyces sp.CS684[J].Process Biochemistry,2010,45(1):88-93.DOI:10.1016/j.procbio.2009.08.010.
[23]王骏,王敏,王以光.链霉菌产生的新型纤溶酶的纯化和性质的研究[J].生物工程学报,1999,(2):147-153.DOI:10.1088/0256-307X/15/12/024.WANG Jun,WANG Min,WANG Yiguang.Purification and characterization of novel plasmin from Streptomyces sp[J].Chinese Journal of Biotechnology,1999,(2):147-153.DOI:10.1088/0256-307X/15/12/024.
[24]龚勇,王以光.一种来源于链霉菌的纤溶酶的纯化及其基因的克隆[J].微生物学报,2001,41(2):186-190.DOI:10.3321/j.issn:0001-6209.2001.02.010.GONG Yong,WANG Yiguang.Purification and gene cloning of a novel fibrinolytic proteasefrom streptomyces SP.C3662[J].Acta Microbiologica Sinica,2001,41(2):186-190.DOI:10.3321/j.issn:0001-6209.2001.02.010.
[25]侯正欣,董超,马萱,等.海洋来源链霉菌MY0504产纤溶酶的发酵条件优化[J].微生物学通报,2017,44(5):1009-1016.DOI:10.13344/j.microbiol.china.160470.HOU Zhengxin,DONG Chao,MA Xuan.Optimization of fermentation for fibrinolytic enzymeproduction by Streptomyces MY0504 from ocean[J].Microbiology,2017,44(5):1009-1016.DOI:10.13344/j.microbiol.china.160470.
[26]刘晨光,魏香,刘万顺.海洋假单胞菌纤溶酶的酶学性质的研究[J].中国海洋大学学报(自然科学版),2001,31(5):730-734.DOI:10.3969/j.issn.1672-5174.2001.05.014.LIU Chenguang,WEI Xiang,LIU Wanshun.Study on characteristics of fibrilytic enzyme from marine pseudomonas[J].Periodical of Ocean University of China,2001,31(5):730-734.DOI:10.3969/j.issn.1672-5174.2001.05.014.
[27]璩竹玲,刘赛,刘晨光,等.海洋假单胞菌碱性蛋白酶的纤溶及抗血栓形成作用[J].青岛大学医学院学报,2003,39(2):156-158.QU Zhuling,LIU Sai,LIU Chenguang.Fibrinolysis and antithrombotic action of alkaline protease of marine pseudomonas sp[J].Acta Academiae Medicinae Qingdao Universitatis,2003,39(2):156-158.
[28]孙哲,孙瑶,王海宽.菊芋小孢根霉固态发酵纤溶酶的工艺优化[J].天津科技大学学报,2013,(2):1-5.SUN Zhe,SUN Yao,WANG Haikuan.Solid-state fermentation of rhizopus microsporus var.tuberosus for production of fibrinolytic enzyme[J].Journal of Tianjing University of Science & Technology,2013,(2):1-5.
[29]高占争,李兆坤,赵允麟,等.米曲霉发酵产纤溶酶培养基的优化[J].河南工业大学学报(自然科学版),2007,28(1):17-20.DOI:10.3969/j.issn.1673-2383.2007.01.005.GAO Zhanzheng,LI Zhaokun,ZHAO Yunlin,et al.Optimizing the medium of asperillus oryzae strains for prdoucing fibrinolytic enzyme[J].Journal of Henan University of Technology (Natural Science Edition),2007,28(1):17-20.DOI:10.3969/j.issn.1673-2383.2007.01.005.
[30]江洁,杜连祥,路福平,等.里氏木霉306生物合成组织型纤溶酶原激活剂(t-PA)5L罐分批发酵条件的研究[J].食品与发酵工业,2005,31(11):18-21.DOI:10.3321/j.issn:0253-990X.2005.11.005.JIANG Jie,DU Lianxiang,LU Fuping,et al.Study on the batch fermentation conditions of tissue-type plasminogen activator (t-PA) producing by trichoderma reesei 306[J].Food and Fermentation Industries,2005,31(11):18-21.DOI:10.3321/j.issn:0253-990X.2005.11.005.
[31]许爱清,刘晓兰,吴耘红,等.高产纤溶酶的脉孢霉诱变育种研究[J].齐齐哈尔大学学报:自然科学版,2003,(4):5-7.XU Aiqing,LIU Xiaolan,WU Yunhong,et al.Study on mutagenesis breeding of high fibrinolytic enzyme producing Neurospora sitophila[J].Journal of Qiqihar University ,2003,(4):5-7.
[32]吴黎诚.镰孢霉CPCC 480097来源的纤溶酶的研究[M].沈阳:沈阳药科大学,2008.WU Licheng.Study on plasmin from fusarium falciparum CPCC 480097[M].Shenyang:Shenyang Pharmaceutical University,2008.
[33]张静如.白僵菌纤溶酶(fibrinolytic enzyme)之分离纯化与特性研究[D].台北:朝阳科技大学生物技术研究所,2006.ZHANG Jingru.Purification and characterization of fibrinolytic enzymes from beauveria bassiana[D].Taipei:Institute of Biotechnology,Chaoyang University of Science and Technology,2006.
[34]LI H P,HU Z,YUAN J L,et al.A novel extracellular protease with fibrinolytic activity from the culture supernatant of Cordyceps sinensis:Purification and characterization[J].Phytotherapy Research,2007,21(12):1234-1241.DOI:10.1002/ptr.2246.
[35]陈慧鑫,刘晓兰,李巍巍,等.蛹虫草深层培养产纤溶酶条件的优化[J].食品工业科技,2010,31(11):216-220.CHEN Huixin,LIU Xiaolan,LI Weiwei,et al.Optimization of submerged culture conditions for the production of fibrinolytic enzyme with Cordyceps militaris[J].Science and Technology of Food Industry,2010,31(11):216-220.
[36]崔莉,董明盛,陈晓红,等.一株纤溶酶产生菌——蛹虫草的形态和分子鉴定[J].江苏农业学报,2010,26(3):667-669.DOI:10.3969/j.issn.1000-4440.2010.03.044.CUI Li,DONG Mingsheng,CHEN Xiaohong,et al.Morphological and molecular identificationof a cordyceps militaris producing thrombolytic enzyme[J].Jiangsu Journal of Agricultural Sciences,2010,26(3):667-669.DOI:10.3969/j.issn.1000-4440.2010.03.044.
[37]沈明花,金成俊.榆干离褶伞溶栓酶的纯化及酶学性质研究[J].食品与发酵工业,2007,33(8):45-47.SHEN Minghua,JIN Chengjun.Purification of fibrinolytic enzyme from cultured mycelia of lyophyllum ulmarium[J].Food and Fermentation Industries,2007,33(8):45-47.
[38]徐德钦,陈海燕,章海锋,等.黄绿蜜环菌产纤溶酶的发酵条件优化研究[J].中国食品学报,2009,9(6):96-103.DOI:10.3969/j.issn.1009-7848.2009.06.016.XU Deqin,CHEN Haiyan,ZHANG Haifeng,et al.Studies on the fermentation condition optimization of fibrinolytic enzyme produced by armiilaria luteo-virens sacc[J].Journal of Chinese Institute of Food Science and Technology,2009,9(6):96-103.DOI:10.3969/j.issn.1009-7848.2009.06.016.
[39]VIJAYARAGHAVAN P,PRAKASH VINCENT S G.A low cost fermentation medium for potential fibrinolytic enzyme production by a newly isolated marine bacterium,Shewanella sp.IND20[J].Biotechnology Reports,2015,7:135.DOI:10.1016/j.btre.2015.06.005.
[40]李占强,胡江春,王书锦.响应曲面法优化海洋Bacillus pumilus B5815产纤溶酶培养基[C].杭州:全国抗生素,2009.LI Zhanqiang,HU Jiangchun,WANG Shujin.Response surface method was used to optimize Marine Bacillus pumilus B5815 fibrinolytic enzyme production medium[C].Hangzhou:National Antibiotic,2009.
[41]赵红,程洁,陆俭,等.产芽孢梭菌纤溶酶的纯化及特性[J].中国生物制品学杂志,2002,15(1):27-31.DOI:10.3969/j.issn.1004-5503.2002.01.008.ZHAO Hong,CHENG Jie,LU Jian,et al.Purification and characterization of fibrinolytic enzyme of c.sporogenes strain[J].Chinese Journal of Biologicals,2002,15(1):27-31.DOI:10.3969/j.issn.1004-5503.2002.01.008.
[42]肖璐,张仁怀,张义正.纤溶酶产生菌-藤黄微球菌的筛选、鉴定及纤溶酶基因的克隆[J].微生物学通报,2008,35(9):1443-1449.XIAO Lu,ZHANG Renhuai,ZHANG Yizheng.Isolation of a micrococcus luteus strain with producing fibrinolysin and cloning of fibrinolitic enzyme gene[J].Microbiology,2008,35(9):1443-1449.
[43]王高学,黄海洪,张明.一株青藏高原冻土溶栓菌的筛选及鉴定[J].微生物学报,2010,50(2):148-154.DOI:10.13343/j.cnki.wsxb.2010.02.008.WANG Gaoxue,HUANG Haihong,ZHANG Ming.Isolation and identification of a fibrinolytic bacterium strain from frozen soil in the Tibetan Plateau[J].Acta Microbiologica Sinica,2010,50(2):148-154.DOI:10.13343/j.cnki.wsxb.2010.02.008.
[44]和七一,文浩平,张康,等.产纤溶酶菌株粪肠球菌EF608液体发酵工艺优化研究[J].食品工业科技,2012,33(15):165-168.HE Qiyi,WEN Haoping,ZHANG Kang,et al.Optimization of fermentation process on a fibrinolytic enzyme from Enterococcus faecalis EF608[J].Science and Technology of Food Industry,2012,33(15):165-168.
[2]吕翠平,董小黎.肺血栓栓塞的治疗进展[J].临床荟萃,2005,20(14):836-838.DOI:10.3969/j.issn.1004-583X.2005.14.039.Lü Cuiping,DONG Xiaoli.Treatment progress in pulmonary thromboembolism[J].Clinical Focus,2005,20(14):836-838.DOI:10.3969/j.issn.1004-583X.2005.14.039.
[3]LOSI M A,GOLINO P,BETOCCHI S,et al.Massive chronic atrial thrombosis[J].International Journal of Cardiology,2003,90(2):323-324.DOI:10.1016/S0167-5273(02)00508-9.
[4]奉涛.溶栓药物的临床应用及其进展[J].临床合理用药杂志,2011,04(17):145-146.DOI:10.3969/j.issn.1674-3296.2011.17.132.FENG Tao.Advancement and clinical application on thrombolytic[J].Chinese Journal of Clinical Rational Drug Use,2011,04(17):145-146.DOI:10.3969/j.issn.1674-3296.2011.17.132.
[5]NELSON H,SARGENT D J,WIEAND H S,et al.A comparison of laparoscopically assisted and open colectomy for colon cancer[J].New England Journal of Medicine,2004,350(20):2050-2059.DOI:10.1056/NEJMoa032651.
[6]SUMNER-SMITH G.The safety and tolerability of lumbrokinase DLBS1033 in healthy adult subjects[J].Drug Research,2016,66(06):293-299.DOI:10.1055/s-0035-1569406.
[7]梁鹏宇,潘霞,任宇豪.溶栓酶的研究进展[J].广西科学,2017,24(1):77-82.DOI:10.13656/j.cnki.gxkx.20170116.002.LIANG Pengyu,PAN Xia,REN Yuhao.Research progress of thrombolytic enzymes[J].Guangxi Science,2017,24(1):77-82.DOI:10.13656/j.cnki.gxkx.20170116.002.
[8]高春杰,张爱香,陈轶暖.蛇毒酶(抗凝溶栓)制剂的应用研究[J].中国医药指南,2010,08(19):235-236.DOI:10.3969/j.issn.1671-8194.2010.19.079.GAO Chunjie,ZHANG Aixiang,CHEN Yinuan.Application of snake venom enzyme (anticoagulant thrombolytic) preparation[J].Guide of China Medicine,2010,08(19):235-236.DOI:10.3969/j.issn.1671-8194.2010.19.079.
[9]曹郁.蛇毒纤溶酶原激活剂TSV-PA在昆虫细胞中的表达[J].生物工程学报,2001,17(5):506-509.DOI:10.3321/j.issn:1000-3061.2001.05.007.CAO Yu.Expression of a snake venom plasminogen activator TSV-PA in insect cells[J].Chinese Journal of Biotechnology,2001,17(5):506-509.DOI:10.3321/j.issn:1000-3061.2001.05.007.
[10]GARDELL S J,DUONG L T,DIEHL R E,et al.Isolation,characterization,and cDNA cloning of a vampire bat salivary plasminogen activator[J].Journal of Biological Chemistry,1989,264(30):17947.DOI:10.1016/S0005-2728(89)80013-1.
[11]MA D,MIZURINI D M,ASSUMPCAO T C F,et al.Desmolaris,a novel factor XIa anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in vivo[J].Blood,2013,122(25):4094-4106.DOI:10.1182/blood-2013-08-517474.
[12]刘堰,苏畅,宋小双,等.表达食血蝙蝠唾液纤溶酶原激活剂的毕赤酵母菌株的构建[J].生物工程学报,2009,25(4):566-574.DOI:10.3321/j.issn:1000-3061.2009.04.015.LIU Yan,SU Chang,SONG Xiaoshuang,et al.Construction of pichia pastoris strain expressing salivary plasminogen activator from vampire bat (Desmodus rotundus)[J].Chinese Journal of Biotechnology,2009,25(4):566-574.DOI:10.3321/j.issn:1000-3061.2009.04.015.
[13]HILDEBRANDT J P,LEMKE S.Small bite,large impact-saliva and salivary molecules in the medicinal leech,Hirudo medicinalis[J].Naturwissenschaften,2011,98(12):995-1008.DOI:10.1016/j.radonc.2005.10.002.
[14]徐文杰,谭树华.乳酸菌表达的重组水蛭素的壳聚糖微粒的口服药效学研究[J].药物生物技术,2014(6):547-549.DOI:10.19526/j.cnki.1005-8915.2014.06.013.XU Wenjie,TAN Shuhua.Oral pharmacodynamics of chitosan particles expressed by lactobacillus recombinant hirudin[J].Pharmaceutical Biotechnology,2014(6):547-549.DOI:10.19526/j.cnki.1005-8915.2014.06.013.
[15]丁文惠,高亢.基因重组链激酶静脉溶栓治疗急性心肌梗塞临床研究[J].中国临床药理学杂志,2000,16(4):259-261.DOI:10.3969/j.issn.1001-6821.2000.04.005.DING Wenhui,GAO Kang.Intravenous thrombolysis in patients with acute myocardial infarction-comparison of the efficacy of gene recombined streptokinase[J].The Chinese Journal of Clinical Pharmacology,2000,16(4):259-261.DOI:10.3969/j.issn.1001-6821.2000.04.005.
[16]熊晓辉,梁剑光,熊强.纳豆激酶液体发酵条件的优化[J].食品与发酵工业,2004,30(1):62-66.DOI:10.3321/j.issn:0253-990X.2004.01.016.XIONG Xiaohui,LIANG Jianguang,XIONG Qiang.Optimization of Nattokinase production using liquid fermentation[J].Food and Fermentation Industries,2004,30(1):62-66.DOI:10.3321/j.issn:0253-990X.2004.01.016.
[17]董超,李楠,程辉彩,等.纳豆激酶发酵条件的优化[J].食品科学,2009,30(1):151-154.DOI:10.3321/j.issn:1002-6630.2009.01.036.DONG Chao,LI Nan,CHENG Huicai,et al.Optimization of fermentation conditions for production of Nattokinase[J].Food Science,2009,30(1):151-154.DOI:10.3321/j.issn:1002-6630.2009.01.036.
[18]韩慧明,李咏梅.纳豆激酶基因在大肠杆菌中的表达及活性分析[J].中国生物工程杂志,2014,34(10):49-54.DOI:10.13523/j.cb.20141008.HAN Huiming,LI Yongmei.Secretory expression of Nattokinase from Bacillus natto in Escherichia coli[J].China Biotechnology,2014,34(10):49-54.DOI:10.13523/j.cb.20141008.
[19]CHITTE R R,DEY S.Potent fibrinolytic enzyme from a thermophilic Streptomyces megasporus strain SD5[J].Letters in Applied Microbiology,2010,31(6):405-410.DOI:10.1046/j.1365-2672.2000.00831.x.
[20]CHITTE R R,DEY S.Production of a fibrinolytic enzyme by thermophilic Streptomyces species[J].World Journal of Microbiology and Biotechnology,2002,18(4):289-294.DOI:10.1023/a:1015252607118.
[21]MANDER P,CHO S S,SIMKHADA J R,et al.A low molecular weight chymotrypsin-like novel fibrinolytic enzyme from Streptomyces sp.CS624[J].Process Biochemistry,2011,46(7):1449-1455.DOI:10.1016/j.procbio.2011.03.016.
[22]SIMKHADA J R,MANDER P,CHO S S,et al.A novel fibrinolytic protease from Streptomyces sp.CS684[J].Process Biochemistry,2010,45(1):88-93.DOI:10.1016/j.procbio.2009.08.010.
[23]王骏,王敏,王以光.链霉菌产生的新型纤溶酶的纯化和性质的研究[J].生物工程学报,1999,(2):147-153.DOI:10.1088/0256-307X/15/12/024.WANG Jun,WANG Min,WANG Yiguang.Purification and characterization of novel plasmin from Streptomyces sp[J].Chinese Journal of Biotechnology,1999,(2):147-153.DOI:10.1088/0256-307X/15/12/024.
[24]龚勇,王以光.一种来源于链霉菌的纤溶酶的纯化及其基因的克隆[J].微生物学报,2001,41(2):186-190.DOI:10.3321/j.issn:0001-6209.2001.02.010.GONG Yong,WANG Yiguang.Purification and gene cloning of a novel fibrinolytic proteasefrom streptomyces SP.C3662[J].Acta Microbiologica Sinica,2001,41(2):186-190.DOI:10.3321/j.issn:0001-6209.2001.02.010.
[25]侯正欣,董超,马萱,等.海洋来源链霉菌MY0504产纤溶酶的发酵条件优化[J].微生物学通报,2017,44(5):1009-1016.DOI:10.13344/j.microbiol.china.160470.HOU Zhengxin,DONG Chao,MA Xuan.Optimization of fermentation for fibrinolytic enzymeproduction by Streptomyces MY0504 from ocean[J].Microbiology,2017,44(5):1009-1016.DOI:10.13344/j.microbiol.china.160470.
[26]刘晨光,魏香,刘万顺.海洋假单胞菌纤溶酶的酶学性质的研究[J].中国海洋大学学报(自然科学版),2001,31(5):730-734.DOI:10.3969/j.issn.1672-5174.2001.05.014.LIU Chenguang,WEI Xiang,LIU Wanshun.Study on characteristics of fibrilytic enzyme from marine pseudomonas[J].Periodical of Ocean University of China,2001,31(5):730-734.DOI:10.3969/j.issn.1672-5174.2001.05.014.
[27]璩竹玲,刘赛,刘晨光,等.海洋假单胞菌碱性蛋白酶的纤溶及抗血栓形成作用[J].青岛大学医学院学报,2003,39(2):156-158.QU Zhuling,LIU Sai,LIU Chenguang.Fibrinolysis and antithrombotic action of alkaline protease of marine pseudomonas sp[J].Acta Academiae Medicinae Qingdao Universitatis,2003,39(2):156-158.
[28]孙哲,孙瑶,王海宽.菊芋小孢根霉固态发酵纤溶酶的工艺优化[J].天津科技大学学报,2013,(2):1-5.SUN Zhe,SUN Yao,WANG Haikuan.Solid-state fermentation of rhizopus microsporus var.tuberosus for production of fibrinolytic enzyme[J].Journal of Tianjing University of Science & Technology,2013,(2):1-5.
[29]高占争,李兆坤,赵允麟,等.米曲霉发酵产纤溶酶培养基的优化[J].河南工业大学学报(自然科学版),2007,28(1):17-20.DOI:10.3969/j.issn.1673-2383.2007.01.005.GAO Zhanzheng,LI Zhaokun,ZHAO Yunlin,et al.Optimizing the medium of asperillus oryzae strains for prdoucing fibrinolytic enzyme[J].Journal of Henan University of Technology (Natural Science Edition),2007,28(1):17-20.DOI:10.3969/j.issn.1673-2383.2007.01.005.
[30]江洁,杜连祥,路福平,等.里氏木霉306生物合成组织型纤溶酶原激活剂(t-PA)5L罐分批发酵条件的研究[J].食品与发酵工业,2005,31(11):18-21.DOI:10.3321/j.issn:0253-990X.2005.11.005.JIANG Jie,DU Lianxiang,LU Fuping,et al.Study on the batch fermentation conditions of tissue-type plasminogen activator (t-PA) producing by trichoderma reesei 306[J].Food and Fermentation Industries,2005,31(11):18-21.DOI:10.3321/j.issn:0253-990X.2005.11.005.
[31]许爱清,刘晓兰,吴耘红,等.高产纤溶酶的脉孢霉诱变育种研究[J].齐齐哈尔大学学报:自然科学版,2003,(4):5-7.XU Aiqing,LIU Xiaolan,WU Yunhong,et al.Study on mutagenesis breeding of high fibrinolytic enzyme producing Neurospora sitophila[J].Journal of Qiqihar University ,2003,(4):5-7.
[32]吴黎诚.镰孢霉CPCC 480097来源的纤溶酶的研究[M].沈阳:沈阳药科大学,2008.WU Licheng.Study on plasmin from fusarium falciparum CPCC 480097[M].Shenyang:Shenyang Pharmaceutical University,2008.
[33]张静如.白僵菌纤溶酶(fibrinolytic enzyme)之分离纯化与特性研究[D].台北:朝阳科技大学生物技术研究所,2006.ZHANG Jingru.Purification and characterization of fibrinolytic enzymes from beauveria bassiana[D].Taipei:Institute of Biotechnology,Chaoyang University of Science and Technology,2006.
[34]LI H P,HU Z,YUAN J L,et al.A novel extracellular protease with fibrinolytic activity from the culture supernatant of Cordyceps sinensis:Purification and characterization[J].Phytotherapy Research,2007,21(12):1234-1241.DOI:10.1002/ptr.2246.
[35]陈慧鑫,刘晓兰,李巍巍,等.蛹虫草深层培养产纤溶酶条件的优化[J].食品工业科技,2010,31(11):216-220.CHEN Huixin,LIU Xiaolan,LI Weiwei,et al.Optimization of submerged culture conditions for the production of fibrinolytic enzyme with Cordyceps militaris[J].Science and Technology of Food Industry,2010,31(11):216-220.
[36]崔莉,董明盛,陈晓红,等.一株纤溶酶产生菌——蛹虫草的形态和分子鉴定[J].江苏农业学报,2010,26(3):667-669.DOI:10.3969/j.issn.1000-4440.2010.03.044.CUI Li,DONG Mingsheng,CHEN Xiaohong,et al.Morphological and molecular identificationof a cordyceps militaris producing thrombolytic enzyme[J].Jiangsu Journal of Agricultural Sciences,2010,26(3):667-669.DOI:10.3969/j.issn.1000-4440.2010.03.044.
[37]沈明花,金成俊.榆干离褶伞溶栓酶的纯化及酶学性质研究[J].食品与发酵工业,2007,33(8):45-47.SHEN Minghua,JIN Chengjun.Purification of fibrinolytic enzyme from cultured mycelia of lyophyllum ulmarium[J].Food and Fermentation Industries,2007,33(8):45-47.
[38]徐德钦,陈海燕,章海锋,等.黄绿蜜环菌产纤溶酶的发酵条件优化研究[J].中国食品学报,2009,9(6):96-103.DOI:10.3969/j.issn.1009-7848.2009.06.016.XU Deqin,CHEN Haiyan,ZHANG Haifeng,et al.Studies on the fermentation condition optimization of fibrinolytic enzyme produced by armiilaria luteo-virens sacc[J].Journal of Chinese Institute of Food Science and Technology,2009,9(6):96-103.DOI:10.3969/j.issn.1009-7848.2009.06.016.
[39]VIJAYARAGHAVAN P,PRAKASH VINCENT S G.A low cost fermentation medium for potential fibrinolytic enzyme production by a newly isolated marine bacterium,Shewanella sp.IND20[J].Biotechnology Reports,2015,7:135.DOI:10.1016/j.btre.2015.06.005.
[40]李占强,胡江春,王书锦.响应曲面法优化海洋Bacillus pumilus B5815产纤溶酶培养基[C].杭州:全国抗生素,2009.LI Zhanqiang,HU Jiangchun,WANG Shujin.Response surface method was used to optimize Marine Bacillus pumilus B5815 fibrinolytic enzyme production medium[C].Hangzhou:National Antibiotic,2009.
[41]赵红,程洁,陆俭,等.产芽孢梭菌纤溶酶的纯化及特性[J].中国生物制品学杂志,2002,15(1):27-31.DOI:10.3969/j.issn.1004-5503.2002.01.008.ZHAO Hong,CHENG Jie,LU Jian,et al.Purification and characterization of fibrinolytic enzyme of c.sporogenes strain[J].Chinese Journal of Biologicals,2002,15(1):27-31.DOI:10.3969/j.issn.1004-5503.2002.01.008.
[42]肖璐,张仁怀,张义正.纤溶酶产生菌-藤黄微球菌的筛选、鉴定及纤溶酶基因的克隆[J].微生物学通报,2008,35(9):1443-1449.XIAO Lu,ZHANG Renhuai,ZHANG Yizheng.Isolation of a micrococcus luteus strain with producing fibrinolysin and cloning of fibrinolitic enzyme gene[J].Microbiology,2008,35(9):1443-1449.
[43]王高学,黄海洪,张明.一株青藏高原冻土溶栓菌的筛选及鉴定[J].微生物学报,2010,50(2):148-154.DOI:10.13343/j.cnki.wsxb.2010.02.008.WANG Gaoxue,HUANG Haihong,ZHANG Ming.Isolation and identification of a fibrinolytic bacterium strain from frozen soil in the Tibetan Plateau[J].Acta Microbiologica Sinica,2010,50(2):148-154.DOI:10.13343/j.cnki.wsxb.2010.02.008.
[44]和七一,文浩平,张康,等.产纤溶酶菌株粪肠球菌EF608液体发酵工艺优化研究[J].食品工业科技,2012,33(15):165-168.HE Qiyi,WEN Haoping,ZHANG Kang,et al.Optimization of fermentation process on a fibrinolytic enzyme from Enterococcus faecalis EF608[J].Science and Technology of Food Industry,2012,33(15):165-168.