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Identification and fibrinolytic Evaluation of an Isoindolone Derivative Isolated from a Rare Marine Fungus Stachybotrys Iongispora FG216

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Chinese Journal of Chemistry 2015年第9期33卷 1089-1095页

作者： Ge Wang Wenhui Wu Quangang Zhu Shiqing Fu Xiaoyu Wang Shaotong Hong Ruihua Guo Bin Bao College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China Institute of Marine Science Shanghai Ocean University Shanghai 201306 China Department of Chinese Pharmacy Yueyang Hospital of Integrated Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Shanghai 200437 China Shanghai Engineering Research Center of Aquatic-Product Processing andPreservation Shanghai 201306 China

An isoindolone derivative, Fungi fibrinolytic compound （R）-2,5-bis（（2R,3R）-2-（（E）-4,8-dimethylnona-3,7-dien- 1-y1）-3,5-dihydroxy-2-methy--7-oxo-3,4,7,9-tetrahydr pyrano[2,3-e]isoindol-8（2H）-yl）pentanoic acid （FGFC1, Fungi fibrinolytic compound 1）, was isolated from a rare marine microorganism strain Stachybotrys longispora FG216. The structure of FGFC1 was elucidated by 1H NMR, 13C NMR, IR, and MS data; moreover, it was also evaluated for fibrinolytic activity in vitro and in vivo. The results showed that 0.1--0.4 mmol/L of FGFC1 could stimulate generation of plasmin activity （increased by 2.05--11.44 folds） by measuring Glu-plasminogen and Lys-plasminogen activation in vitro. The experiment of fluorescein isothiocyanate （FITC）-fibrinogen degradation indicated that the effect of FGFCI on fibrinolytic activity was mediated by plasminogen and scuPA. In addition, FGFC 1 （10 mg/kg） could dissolve most of pulmonary thrombus of Wistar rat in vivo. It is possible that FGFC 1 is a potential thrombolytic agent in the future.

关键词： Stachybotrys longispora FG216 marine microorganism plasmin activity fibrinolytic activity

fibrinolytic Evaluation of Compounds Isolated from a Marine Fungus Stachybotrys Iongispora FG216

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Chinese Journal of Chemistry 2016年第11期34卷 1194-1198页

作者： Ruihua Guo Yiting Zhang Dong Duan Qiang Fu Xiangyu Zhang Xiaowei Yu Shujun Wang Bin Bao Wenhui Wu College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China Institute of Marine Science Shanghai Ocean University Shanghai 201306 China Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation Shanghai 201306 China East Hospital of Shanghai No. 6 People's Hospital Shanghai 201306 China Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening Huaihai Institute of Technology Lianyungang Jiangsu 222005 China

As a part of our continuing work to discover bioactive leading molecules from marine microorganism, ethyl acetate fraction of organic extract of the train Stachybotrys longispora FG216 showed fibrinolytic activity in our primary screen. The bioassay-guided purification of the active fractions resulted in isolation of a new isoindolone, FGFC2 （1）（FGFC2, Fungi fibrinolytic compound 2）, together with two known compounds, LL-Zl272β （2） and ergosterol （3）. The structure of compound 1 was elucidated by the spectral analysis of 1D （^1H, ^13C） NMR, 2D （COSY, HSQC, and HMBC） and ESI-MS. Three compounds were evaluated for fibrinolytic activities in vitro. Compared to FGFC1 （EC50=47 μmol/L） as a reference drug, compound 1 and ergosterol （3） showed moderate fibrinolytic activities in vitro with EC50 values of 108.16 and 156.30 μmol/L, respectively. LL-Z127213 （2） had no fibrinolytic activity.

关键词： Stachybotrys longispora FG216 marine microorganism fibrinolytic activity isoindolone

Preparation of pegylated lumbrokinase and an evaluation of its thrombolytic activity both in vitro and in vivo

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Acta Pharmaceutica Sinica B 2013年第2期3卷 123-129页

作者： Mingji Jin Wei Chen Wei Huang Long Rong Zhonggao Gao State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of Drug Delivery Technology and Novel FormulationsInstitute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China Beijing University of Aeronautics and Astronautics Beijing 100191China

Lumbrokinase(LK)is a group of serine proteases with strong fibrinolytic and thrombolytic *** clinical practice,LK can only be administered orally because of its antigenicity,iinmunogenicity and potential to produce anaphylactic reactions after ***,many useful drugs such as interferon,insulin,erythropoietin and interleukin have been modified with polyethylene glycol(PEG)to prepare injectable *** this study,LK was modified with methoxy PEG succinimidyl carbonate(mPEG-SC)with molecular weights of 5000,10,000 and 20,000 and the pegylatcd products were isolated and purified using the Akta protein purification *** extent of pegylation was detennined by *** activities of pegylatcd and unmodified LK were measured both in vitro against urokinase on fibrin plates and in vivo using a mouse carageenan black tail *** pegylation was obtainal using mPEG-SC_(5000) in a buffer pH 8.0 with a reaction time of 5 h,reaction temperature of 0℃ and LK:mPEG-SC molar ratio of 1:*** results show that mPEG modified LK has strong fibrinolytic and thrombolytic activities both in vitro and in *** is suggested that the pegylatcd LK is a promising injectable thrombolytic agent for the treatment of thrombotic diseases in clinical practice.

关键词： Lumbrokinase Methoxy polyethylene glycol succinimidyl carbonate Pegylation fibrinolytic activity

口服避孕药对妇女血小板聚集程度、血浆纤维蛋白原及纤溶活性的影响

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生殖与避孕 1984年第1期 23-27页

作者：汪钟高海泉安岩时其煌朱国强张志荣中国医学科学院基础医学研究所

本文观察了先服短效复方18甲、后改服减量长效复方18甲的已婚育龄妇女的ADP诱导血小板聚集程度、血浆纤维蛋白原、纤溶酶原及血清纤维蛋白原裂解产物(FDP)含量的变化,并以相似年龄的正常志愿者作为对照。结果:服全量长效复方18甲妇女的... 详细信息

本文观察了先服短效复方18甲、后改服减量长效复方18甲的已婚育龄妇女的ADP诱导血小板聚集程度、血浆纤维蛋白原、纤溶酶原及血清纤维蛋白原裂解产物(FDP)含量的变化,并以相似年龄的正常志愿者作为对照。结果:服全量长效复方18甲妇女的血小板聚集程度较服药前显著增加,但停药后恢复至正常水平,表明对血小板聚集程度的影响是可逆的。服减量长效复方18甲妇女的血小板聚集程度低于正常水平。无论服短效复方18甲还是服减量长效复方18甲三个月、半年时,纤维蛋白原含量均较对照组高,但服减量长效复方18甲一年后其含量恢复至正常范围。此外,服减量长效复方18甲妇女的纤溶酶原含量较对照组高,但FDP水平均在正常范围内。

关键词： Oral contraceptive Platelet aggregation Plasma fibrinogen fibrinolytic activity

宫内节育器引起月经过多者纤溶酶元,纤溶活性,过氧化氢酶变化及维生素E治疗观察

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生殖与避孕 1987年第3期 59-61页

作者：张鹏程樊瑞琴陈晓梅河北省计划生育研究所生化研究室

本文对31例置器妇女月经血量过多者的月经血和外周血中纤溶酶元、纤溶活性及过氧化氢酶含量进行了测定。同时观察了20例月经过多者维生素E治疗前后月经血量和过氧化氢酶含量的变化。结果表明,月经血中纤溶活性、过氧化氢酶含量显著增高(... 详细信息

本文对31例置器妇女月经血量过多者的月经血和外周血中纤溶酶元、纤溶活性及过氧化氢酶含量进行了测定。同时观察了20例月经过多者维生素E治疗前后月经血量和过氧化氢酶含量的变化。结果表明,月经血中纤溶活性、过氧化氢酶含量显著增高(P0.05).维生素E治疗后月经血量下降率为35.21%,过氧化氢酶有明显降低(P<0.01)。提示IUD_S引起月经血过多与纤溶活性及过氧化氢酶之间有密切关系。但IUD_S对子宫出血的影响仅限于局部。

关键词： fibrinolytic activity Peroxidase Plasminogen Menorrhagia blood IUD VitaminE

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正常妇女经血中FDP含量的测定

生殖与避孕 1984年第4期 47-49页

作者：周凤鑫王振义杨君蕊陈珠萍潘家骧上海第二医学院上海第二医学院附属第三人民医院

测量经血中纤维蛋白(原)降解产物(FDP)的含量能作为反映行经时子宫腔内纤溶活力的一种指标,从而间接地确定月经过多与纤溶活力之间的关系。本文报道了兔抗人纤维蛋白原特异性抗血清的制备及以免疫双扩散法测定了43名正常成年妇女经血中... 详细信息

测量经血中纤维蛋白(原)降解产物(FDP)的含量能作为反映行经时子宫腔内纤溶活力的一种指标,从而间接地确定月经过多与纤溶活力之间的关系。本文报道了兔抗人纤维蛋白原特异性抗血清的制备及以免疫双扩散法测定了43名正常成年妇女经血中FDP含量,多数正常妇女经血上清液在稀释度为1:32或1:64时仍有阳性沉淀性可见,其中倍数是1:32相当于144毫克/100毫升的浓度。

关键词： FDP Menstrual blood fibrinolytic activity

Construction of pcDNA3. 1 (+)tPA expression vector

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中国临床神经科学 2000年第Z1期8卷 58-页

作者： ZHAO Yongbo Ll Yu ZHANG Guiyin Department of Neurology TheSecond Affiliated HospitalHarbin Medical University Harbin 150086 Department of Neurology TheSecond Affiliated HospitalHarbin Medical University Harbin 150086 Department of Neurology TheSecond Affiliated HospitalHarbin Medical University Harbin 150086

Objective To construct a new kind of recombinant vector containing human tissue-type plasminogen activator(t-PA) cDNA for studing the feasibility of enhancing fibrinolytic activity by transplantation of genetic engineering cells. Methods We recombinated human tPA cDNA with expression vector pcDNA3. 1 (+) by using the method of molecular cloning, sequenced the plasmid DNA, and cut the plasmid by using enzymes. Results The plasmid pcDNA3.1(+)tPA was divided into 5.4Kb and 2.0Kb segments respectively by using Kpn 1 and Xba I, into 78bp, 414bp, 622bp, 2.0Kb, and4.2Kb segments respectively by tsing Pst l, into 472bp and 6.9Kb segments respectively by using EcoR I. Sequencing result showed that it is the whole human tPA cDNA. Conclusion The new kind of recombinant expression vector could serve as new tools and methods for preventing thrombogenic diseases.

关键词： expression vector plasminogen activator fibrinolytic activity genetic engineering recombinant vector molecular cloning plasmid DNA methods for method of