胶陀螺光敏活性及生药学的研究
|
摘要
胶陀螺[Bulgaria inquinans(Pers．)Fr．]属于胶陀螺科的子囊菌。是一种特殊的很有开发潜力的食药兼用菌，具有抗肿瘤、光敏活性、降低血瘀大鼠的红细胞沉降率、抗突变等作用，营养成分的含量也很高。主要分布于我国东北地区，并且在煤矿中不见光的地方常出现此菌。现在国内已有企业将胶陀螺开发成治疗银屑病的新药，日本也在中国大量收购此菌，对袋料栽培和大面积推广需要进一步研究，为今后人工栽培及原料的获得提供依据。随着光动力疗法的深入研究，尤其应明确光敏活性成分及其中毒机理，制定相应的药材质量标准。
本文对胶陀螺生药学方面的研究主要表现在性状特征、显微特征、理化特征及分子鉴定方面。子实体初期呈黄褐色球形，并带有黄棕色麻点，顶端逐渐开裂，产生一至多个不等的裂口，裂口不断扩大，最后整个子实体表面呈黑色皱缩。子囊棒形，外囊盘被由圆形细胞组成，圆形细胞外侧生绒毛，绒毛细胞内含类似载色体的物质；中囊盘被由埋在胶质中的交错菌丝组成。采用子囊孢子弹射分离法所得菌丝有橘黄色菌丝和长有棒状分生孢子的无色有隔菌丝；采用组织分离法所得菌丝无色，其中生有黑褐色或黄棕色的圆形细胞，呈念珠状。胶陀螺子实体DNA序列与组织分离菌种经液体培养获得的菌丝体DNA序列比对，同源性为99.65％，胶陀螺子实体的DNA序列与GenBank数据库中AY789345比对，其同源性为99.80％，说明组织分离得到的菌种稳定可靠，是胶陀螺纯菌种。
本文通过对胶陀螺子实体和发酵过的子实体的提取分离，共得到5个化合物，1个具光敏活性的组分，鉴定其中4个化合物分别为丙二酸，十六酸，4，8-十九碳二烯酸，2，3-邻萘-4-(1-羟基-正丁基)-5-戊内酯，其中后3个化合物为首次从胶陀螺中得到，2，3-邻萘-4-(1-羟基-正丁基)-5-戊内酯为新化合物，光敏活性组分初步断定为苝醌类成分。
从石油醚萃取层中得到的Q组分采用GC-MS联用对其分析，主要检索到22个化合物。从氯仿萃取层中得到的G组分采用GC-MS联用对其分析，主要检索到7个化合物。它们主要是一类极性较小的脂肪族烃及脂肪酸。
通过光敏活性实验表明，胶陀螺丙酮粗提物、丙酮粗提物中萃取得到的氯仿萃取物及从氯仿萃取物中分离得到的Y4组分和Y5组分具有光敏活性，丙酮粗提物1000mg／kg给药的光照组耳指数有显著差异，2000mg／kg的剂量给药的光照组耳指数和皮指数均有有极显著差异。氯仿萃取组分以260mg／kg和520mg／kg的剂量给药的光照组耳指数和皮指数均有极显著差异。Y4组分以200mg／kg给药的光照组耳指数有显著差异，Y5组分以200mg／kg和100mg／kg的剂量给药的光照组耳指数均有极显著差异，Y4组分以200mg／kg及Y5组分以200mg／kg和100mg／kg的剂量给药的光照组皮指数均有极显著差异。光敏活性与剂量间存在一定的量效关系，并且其光敏毒性的发作也有一定的潜伏期。大鼠以丙酮提取物1g／kg连续给药五天，每天照射光两小时，第四天大鼠耳朵开始溃烂，爪子也变得比较紫，第六天耳朵溃烂掉了。大鼠实验也验证了胶陀螺具有光敏活性，并且对见光敏感的部位有很大的损伤。
Bulgaria inquinans is a kind of ascomycete that Belongs to Bulgariaceae. It is a kind of special development potential fungi that to be used of food and medicine concurrently, it has the anti-tumor action, the photoactive activity, reduceing red blood cell rate of sedimentation of blood stasis rat, anti-sudden change and so on. The ingredient content of nutrition is very high. It mainly distributes in northeast area of our country, and this fungi often appear in the aphotic place of the coal mine. Now domestic enterprise has developed new medicine with Bulgaria inquinans treating psoriasis, this fungi also were massively purchased by Japanese from China, the bag material cultivation and the big area generalization needs to further investigation, that will provides the evidence for factitial cultivation and to gain raw material. Along with thorough research of the light power therapy, it should be clear about the photoactive activity constituent and the empoison mechanism especially, to formulate quality specification for the corresponding raw material.
Pharmacognostic research of Bulgaria inquinans displayed that characteristic trait, microscopic trait, physichemical trait and molecular biology trait in this paper, The results showed that fruit bodies were snuff color and dotted with yellowish brown pits at the beginning, and then their upper side split into one or several pores, at last the surface of body turned black and crimpled. The asci are clubbed in shape, the ectal excipulum is made up of circular cells with hairs on the outside which contains chromophore-like substance, the medullary excipulum is consisted of interlaced mycelia imbedded in gelatine. The saffron yellow mycelia and septatus achromatous mycelia with growth clubbed conidium were gained by ascospore discharging method. The mycelia obtained by fruiting body tissue method were hyaline and filamentous, some mycelia composed of circular cell became bead-like, dark brown or yellowish. Comparing the DNA sequences from fruiting body and mycelia gain from liquid culture using strain of tissue culture, their similarity is 99.65%. After comparing the DNA sequences from fruiting body and AY789345 in GenBank, their similarity is 99.80%. The showing of organization separation obtains mushroom Spawn is stable and reliable, it is the pure mushroom spawn of Bulgaria inquinans.
Fruiting body and fermental fruiting body of Bulgaria inquinans were extracted and separated in this article, 5 compounds and 1 component with photoactive activity were obtained in all, expertised 4 compounds, they are aremalonic acid, hexadecanoic acid, 4, 8-nonadecane dienoic acid and 2, 3-consecutive naphthyl-4-(1-hydroxy-normai-butyl)-5-valerolactone respectively. Posterior 3 compounds were separated from Bulgaria inquinans for the first time, 2, 3-consecutive naphthyl-4-(1-hydroxy-normal-butyl)-5- Valerolactone is a new compound. Photoactive activity component was predicated perylenequinones composition preliminarily.
The Q component which obtained from the petroleum ether extract layer was used the GC-MS associated analysis, it mainly retrieved to 22 compounds. The G component which obtained from the chloroform extract layer was used the GC-MS associated analysis, it mainly retrieved to 7 compounds. They are mainly a kind of small polarity fatty group hydrocarbon and the fatty acid.
The extract of acetone, extract of chloroform coming from extract of acetone and Y4 component and Y5 component which separated from the extract of chloroform displayed photoactive activity in photoactive activity experiments. Ear index displayed significant deviation to extract of acetone intragastric administration by 1000mg/kg for illumination series, ear index and skin index displayed extreme significant deviation to extract of acetone intragastric administration by 2000mg/kg for illumination series. Ear index and skin Index displayed extreme significant deviation to extract of chloroform intragastric administration by 260mg/kg and 520mg/kg for illumination series. Ear index displayed significant deviation to Y4 component intragastric administration by 200mg/kg for illumination series, ear index displayed extreme significant deviation to Y5 component intragastric administration by 200mg/kg and 100mg/kg for illumination series, skin Index displayed extreme significant deviation to Y4 component intragastric administration by 200mg/kg and Y5 component intragastric administration by 200mg/kg and 100mg/kg for illumination series. There is Certain dose-effect relationship in the photoactive activity and the dosage, its photoactive toxic attack also has certain dormiens period. Extract of acetone was used in rats through intragastric administration by 1g/kg for 5 days, illumination 2 hour every day, ears of rat started to fester, claws also became quite purple at fourth day, ears was disappeared by fester at sixth day. Photoactive activity of Bulgaria inquinans is also checked by experiment of rat. The locus that is sensitive to light is damaged acutely.
本文对胶陀螺生药学方面的研究主要表现在性状特征、显微特征、理化特征及分子鉴定方面。子实体初期呈黄褐色球形，并带有黄棕色麻点，顶端逐渐开裂，产生一至多个不等的裂口，裂口不断扩大，最后整个子实体表面呈黑色皱缩。子囊棒形，外囊盘被由圆形细胞组成，圆形细胞外侧生绒毛，绒毛细胞内含类似载色体的物质；中囊盘被由埋在胶质中的交错菌丝组成。采用子囊孢子弹射分离法所得菌丝有橘黄色菌丝和长有棒状分生孢子的无色有隔菌丝；采用组织分离法所得菌丝无色，其中生有黑褐色或黄棕色的圆形细胞，呈念珠状。胶陀螺子实体DNA序列与组织分离菌种经液体培养获得的菌丝体DNA序列比对，同源性为99.65％，胶陀螺子实体的DNA序列与GenBank数据库中AY789345比对，其同源性为99.80％，说明组织分离得到的菌种稳定可靠，是胶陀螺纯菌种。
本文通过对胶陀螺子实体和发酵过的子实体的提取分离，共得到5个化合物，1个具光敏活性的组分，鉴定其中4个化合物分别为丙二酸，十六酸，4，8-十九碳二烯酸，2，3-邻萘-4-(1-羟基-正丁基)-5-戊内酯，其中后3个化合物为首次从胶陀螺中得到，2，3-邻萘-4-(1-羟基-正丁基)-5-戊内酯为新化合物，光敏活性组分初步断定为苝醌类成分。
从石油醚萃取层中得到的Q组分采用GC-MS联用对其分析，主要检索到22个化合物。从氯仿萃取层中得到的G组分采用GC-MS联用对其分析，主要检索到7个化合物。它们主要是一类极性较小的脂肪族烃及脂肪酸。
通过光敏活性实验表明，胶陀螺丙酮粗提物、丙酮粗提物中萃取得到的氯仿萃取物及从氯仿萃取物中分离得到的Y4组分和Y5组分具有光敏活性，丙酮粗提物1000mg／kg给药的光照组耳指数有显著差异，2000mg／kg的剂量给药的光照组耳指数和皮指数均有有极显著差异。氯仿萃取组分以260mg／kg和520mg／kg的剂量给药的光照组耳指数和皮指数均有极显著差异。Y4组分以200mg／kg给药的光照组耳指数有显著差异，Y5组分以200mg／kg和100mg／kg的剂量给药的光照组耳指数均有极显著差异，Y4组分以200mg／kg及Y5组分以200mg／kg和100mg／kg的剂量给药的光照组皮指数均有极显著差异。光敏活性与剂量间存在一定的量效关系，并且其光敏毒性的发作也有一定的潜伏期。大鼠以丙酮提取物1g／kg连续给药五天，每天照射光两小时，第四天大鼠耳朵开始溃烂，爪子也变得比较紫，第六天耳朵溃烂掉了。大鼠实验也验证了胶陀螺具有光敏活性，并且对见光敏感的部位有很大的损伤。
Bulgaria inquinans is a kind of ascomycete that Belongs to Bulgariaceae. It is a kind of special development potential fungi that to be used of food and medicine concurrently, it has the anti-tumor action, the photoactive activity, reduceing red blood cell rate of sedimentation of blood stasis rat, anti-sudden change and so on. The ingredient content of nutrition is very high. It mainly distributes in northeast area of our country, and this fungi often appear in the aphotic place of the coal mine. Now domestic enterprise has developed new medicine with Bulgaria inquinans treating psoriasis, this fungi also were massively purchased by Japanese from China, the bag material cultivation and the big area generalization needs to further investigation, that will provides the evidence for factitial cultivation and to gain raw material. Along with thorough research of the light power therapy, it should be clear about the photoactive activity constituent and the empoison mechanism especially, to formulate quality specification for the corresponding raw material.
Pharmacognostic research of Bulgaria inquinans displayed that characteristic trait, microscopic trait, physichemical trait and molecular biology trait in this paper, The results showed that fruit bodies were snuff color and dotted with yellowish brown pits at the beginning, and then their upper side split into one or several pores, at last the surface of body turned black and crimpled. The asci are clubbed in shape, the ectal excipulum is made up of circular cells with hairs on the outside which contains chromophore-like substance, the medullary excipulum is consisted of interlaced mycelia imbedded in gelatine. The saffron yellow mycelia and septatus achromatous mycelia with growth clubbed conidium were gained by ascospore discharging method. The mycelia obtained by fruiting body tissue method were hyaline and filamentous, some mycelia composed of circular cell became bead-like, dark brown or yellowish. Comparing the DNA sequences from fruiting body and mycelia gain from liquid culture using strain of tissue culture, their similarity is 99.65%. After comparing the DNA sequences from fruiting body and AY789345 in GenBank, their similarity is 99.80%. The showing of organization separation obtains mushroom Spawn is stable and reliable, it is the pure mushroom spawn of Bulgaria inquinans.
Fruiting body and fermental fruiting body of Bulgaria inquinans were extracted and separated in this article, 5 compounds and 1 component with photoactive activity were obtained in all, expertised 4 compounds, they are aremalonic acid, hexadecanoic acid, 4, 8-nonadecane dienoic acid and 2, 3-consecutive naphthyl-4-(1-hydroxy-normai-butyl)-5-valerolactone respectively. Posterior 3 compounds were separated from Bulgaria inquinans for the first time, 2, 3-consecutive naphthyl-4-(1-hydroxy-normal-butyl)-5- Valerolactone is a new compound. Photoactive activity component was predicated perylenequinones composition preliminarily.
The Q component which obtained from the petroleum ether extract layer was used the GC-MS associated analysis, it mainly retrieved to 22 compounds. The G component which obtained from the chloroform extract layer was used the GC-MS associated analysis, it mainly retrieved to 7 compounds. They are mainly a kind of small polarity fatty group hydrocarbon and the fatty acid.
The extract of acetone, extract of chloroform coming from extract of acetone and Y4 component and Y5 component which separated from the extract of chloroform displayed photoactive activity in photoactive activity experiments. Ear index displayed significant deviation to extract of acetone intragastric administration by 1000mg/kg for illumination series, ear index and skin index displayed extreme significant deviation to extract of acetone intragastric administration by 2000mg/kg for illumination series. Ear index and skin Index displayed extreme significant deviation to extract of chloroform intragastric administration by 260mg/kg and 520mg/kg for illumination series. Ear index displayed significant deviation to Y4 component intragastric administration by 200mg/kg for illumination series, ear index displayed extreme significant deviation to Y5 component intragastric administration by 200mg/kg and 100mg/kg for illumination series, skin Index displayed extreme significant deviation to Y4 component intragastric administration by 200mg/kg and Y5 component intragastric administration by 200mg/kg and 100mg/kg for illumination series. There is Certain dose-effect relationship in the photoactive activity and the dosage, its photoactive toxic attack also has certain dormiens period. Extract of acetone was used in rats through intragastric administration by 1g/kg for 5 days, illumination 2 hour every day, ears of rat started to fester, claws also became quite purple at fourth day, ears was disappeared by fester at sixth day. Photoactive activity of Bulgaria inquinans is also checked by experiment of rat. The locus that is sensitive to light is damaged acutely.
引文
[1] Sandra OG, Xiaonan L, Barbara O, et al. Alteredexpression of intedeukin 10 as a result of photodynarnic therapy in vivo[J]. Cancer Research. 1997, 57(18): 3904-3909.
[2] Tamara VA, Andrey AR. Insulin-mediated intracellular targeting enhance the photodynamic activity of Chlouine e_6[J]. Cancer Research. 1995, 55(5): 1014-1019.
[3] 陈志龙，万维勤，范开华，等．2，7，12，18-四甲基-3，8-二(1-烷氧乙基)-13，17-二(3-羟基丙基)卟啉衍生物的合成及其光敏活性[J]．中国药物化学杂志，1998，8(1)：1-4．
[4] 苏建伟，范伟民，秦启联，等．光敏活性化合物与害虫治理[J]．植物保护，2002，28(2)：37-39．
[5] Hudson JB, Imperial V, Haugland RP, et al. Antiviral activities of photoactive perylenequinones[J]. Photochemistry and Photobiology, 1997, 65(2): 352-354.
[6] Miller G, Brown K, Ballangrud AM, et al. Preclinical assessment of hypocrellin B and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer progress update[J]. Photochemistry and Photobiology, 1997, 65(4): 714-722.
[7] 罗子华，于兰馥，郭泳芳，等．竹红菌治疗外阴白色病变的临床观察[J]．云南医药，1990，1(1)：20-25．
[8] 王家壁，包建南．皮肤淀粉样变苔藓37例临床分析及竹红菌光化疗法治疗观察[J]．中国医学科学院学报，1985，5(7)：349-351．
[9] 梁睿媛，梅国栋，杨正中，等．竹红菌甲素光治疗肥厚性斑痕62例报告[J]．中华皮肤病杂志，1982，15(2)：87-88．
[10] 周薇，李聪．苝醌化合物的光敏活性及其抗肿瘤机制[J]．生命化学，2001，21(3)：246-247．
[11] 万象义，陈远腾．一种新的光化学疗法药物——竹红菌甲素[J]．科学通报，1980，24(6)：1148-1149．
[12] 王景祥，张黎明，朱丽青，等．竹黄化学成分的研究[J]．中草药，1990，21(1)：4-5
[13] 许德余，殷祥生，陈文晖，等．肿瘤光化学诊治新药癌光啉的研究[J]．中国医药工业杂志，1989，20(10)：440-445．
[14] 余建鑫，张万年，张蕾，等．乙烯基烷氧乙基次卟啉Ⅸ衍生物的合成及其光敏活性[J]．中国药物化学杂志，2000，10(2)：79-83．
[15] Ho YK, Pandey RK, Missert JR, et al. Some components of the tumor-localizing fraction of hematoporphyrin derivative[J]. Photochemistry and Photobiology, 1990, 52(6): 1085-1088.
[16] Kessel D. Hematoporphyrin and HpD: photophysies, photochemistry and phototherapy[J]. Photochemistry and Photobiology, 1984, 39(6): 851-859.
[17] 包海鹰，李玉．胶陀螺营养成分的研究[J]．中国食用菌，2001，20(6)：41-42．
[18] 李茹光．东北大型食用、药用及有毒真菌[M]．长春：东北师范大学出版社，1992，第1版：23-56．
[19] 刘晓龙，刘振钦，李晓，等．胶陀螺菌种分离及驯化栽培研究[J]．吉林农业大学学报，2002，24(2)：75-78．
[20] 包海鹰，李玉．胶陀螺的光敏活性研究[J]．食用菌学报，2002，9(4)：15-17．
[21] 于江，邵志强．胶陀螺中毒3例[J]．牡丹江医学院学报，2002，23(2)：57-58．
[22] 胡建友．胶陀螺中毒二例报告[J]．北京医学，2002，24(3)：216．
[23] 于春波，程彬，宋友，等．胶陀螺人工培养特性的研究[J]．吉林林业科技，2002，31(3)：10-12．
[24] 包海鹰，李玉．胶陀螺化学成分的研究[J]．菌物系统，2003，22(2)：303-30
[25] 崔东滨，王淑琴，丁晓昆．胶陀螺化学成分的研究[J]．中国中药杂志，1997，22(8)：485-486．
[26] Edwards RL, Lockett HJ. Constituents of the higher fungi. Part ⅩⅥ. Bulgarhodin and Bulgarein, Novel benzofluoranthenequinones from the fungus Bulgaria inquinans(Fries)[J]. Journal of the Chemical Society: Perkin Transactions Ⅰ, 1976, 2149-2155.
[27] Stadler M, Anke H, Dekermendjian K, et al. New bioactive azaphilones from the fruit bodies and mycelial cultures of the Ascomycete Bulgaria inquinans (Fr.)[J]. Nature Product Letter, 1995, 7: 7-14
[28] 杨晓静，张泓嵬，孙红，等．胶陀螺的抗肿瘤作用[J]．特产研究，1993，2：9-11
[29] 杨晓静，张树臣，高桂琴，等．胶陀螺对血瘀动物血液流变学的影响[J]．中草药，1996，27(6)：358-359
[30] 王庭欣，秦淑贞，刘燕丽．胶陀螺菌复合制剂抗突变作用的实验研究[J]．中华临床与卫生，2004，3(4)：239-240
[31] 陈明，陈立国，汪国莲．银耳极性测定的初步研究[J]．华中农业大学学报，2000，19(2)：138-141
[32] 胡梅，侯军，胡公洛．草菇组织分离法的改良[J]．食用菌，2001，2：14
[33] 吴志红，汪天虹，黄卫，等．简便易行的丝状真菌染色体DNA提取法[J]．菌物系统，2001，20(4)：575-577．
[34] 李家实．中药鉴定学[M]．上海科学技术出版社，1996，第1版：28-44
[35] 刘淑艳，李玉，白秀娟．一种提取黏菌DNA的新方法[J]．吉林农业大学学报，2001，23(2)：38-40．
[36] 金冬雁，黎孟枫．分子克隆试验指南[M]．北京：科学出版社，1995，第2版：19-56，924-929．
[37] Fenwick GA. A Conidial Form of Bulgaria inquinans[J]. Mycologist, 1992, 6(4): 177-179.
[38] 高锦明．植物化学[M]．北京：科学出版社，2003，第1版：35-37
[39] 肖崇厚．中药化学[M]．上海科学技术出版社，1997，第1版：192-220
[40] 徐叔云，卞如濂，陈修．药理实验方法学[M]．北京：人民卫生出版社，2005．第3版：179-180，195-223
[41] 陈奇．中药药理研究方法学[M]．北京：人民卫生出版社，1996．第1版：37-54，106-108
[42] 王耐勤．血卟啉新分离物—HPS光敏效应的实验研究[J]．肿瘤，1985，5(2)：49
[2] Tamara VA, Andrey AR. Insulin-mediated intracellular targeting enhance the photodynamic activity of Chlouine e_6[J]. Cancer Research. 1995, 55(5): 1014-1019.
[3] 陈志龙，万维勤，范开华，等．2，7，12，18-四甲基-3，8-二(1-烷氧乙基)-13，17-二(3-羟基丙基)卟啉衍生物的合成及其光敏活性[J]．中国药物化学杂志，1998，8(1)：1-4．
[4] 苏建伟，范伟民，秦启联，等．光敏活性化合物与害虫治理[J]．植物保护，2002，28(2)：37-39．
[5] Hudson JB, Imperial V, Haugland RP, et al. Antiviral activities of photoactive perylenequinones[J]. Photochemistry and Photobiology, 1997, 65(2): 352-354.
[6] Miller G, Brown K, Ballangrud AM, et al. Preclinical assessment of hypocrellin B and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer progress update[J]. Photochemistry and Photobiology, 1997, 65(4): 714-722.
[7] 罗子华，于兰馥，郭泳芳，等．竹红菌治疗外阴白色病变的临床观察[J]．云南医药，1990，1(1)：20-25．
[8] 王家壁，包建南．皮肤淀粉样变苔藓37例临床分析及竹红菌光化疗法治疗观察[J]．中国医学科学院学报，1985，5(7)：349-351．
[9] 梁睿媛，梅国栋，杨正中，等．竹红菌甲素光治疗肥厚性斑痕62例报告[J]．中华皮肤病杂志，1982，15(2)：87-88．
[10] 周薇，李聪．苝醌化合物的光敏活性及其抗肿瘤机制[J]．生命化学，2001，21(3)：246-247．
[11] 万象义，陈远腾．一种新的光化学疗法药物——竹红菌甲素[J]．科学通报，1980，24(6)：1148-1149．
[12] 王景祥，张黎明，朱丽青，等．竹黄化学成分的研究[J]．中草药，1990，21(1)：4-5
[13] 许德余，殷祥生，陈文晖，等．肿瘤光化学诊治新药癌光啉的研究[J]．中国医药工业杂志，1989，20(10)：440-445．
[14] 余建鑫，张万年，张蕾，等．乙烯基烷氧乙基次卟啉Ⅸ衍生物的合成及其光敏活性[J]．中国药物化学杂志，2000，10(2)：79-83．
[15] Ho YK, Pandey RK, Missert JR, et al. Some components of the tumor-localizing fraction of hematoporphyrin derivative[J]. Photochemistry and Photobiology, 1990, 52(6): 1085-1088.
[16] Kessel D. Hematoporphyrin and HpD: photophysies, photochemistry and phototherapy[J]. Photochemistry and Photobiology, 1984, 39(6): 851-859.
[17] 包海鹰，李玉．胶陀螺营养成分的研究[J]．中国食用菌，2001，20(6)：41-42．
[18] 李茹光．东北大型食用、药用及有毒真菌[M]．长春：东北师范大学出版社，1992，第1版：23-56．
[19] 刘晓龙，刘振钦，李晓，等．胶陀螺菌种分离及驯化栽培研究[J]．吉林农业大学学报，2002，24(2)：75-78．
[20] 包海鹰，李玉．胶陀螺的光敏活性研究[J]．食用菌学报，2002，9(4)：15-17．
[21] 于江，邵志强．胶陀螺中毒3例[J]．牡丹江医学院学报，2002，23(2)：57-58．
[22] 胡建友．胶陀螺中毒二例报告[J]．北京医学，2002，24(3)：216．
[23] 于春波，程彬，宋友，等．胶陀螺人工培养特性的研究[J]．吉林林业科技，2002，31(3)：10-12．
[24] 包海鹰，李玉．胶陀螺化学成分的研究[J]．菌物系统，2003，22(2)：303-30
[25] 崔东滨，王淑琴，丁晓昆．胶陀螺化学成分的研究[J]．中国中药杂志，1997，22(8)：485-486．
[26] Edwards RL, Lockett HJ. Constituents of the higher fungi. Part ⅩⅥ. Bulgarhodin and Bulgarein, Novel benzofluoranthenequinones from the fungus Bulgaria inquinans(Fries)[J]. Journal of the Chemical Society: Perkin Transactions Ⅰ, 1976, 2149-2155.
[27] Stadler M, Anke H, Dekermendjian K, et al. New bioactive azaphilones from the fruit bodies and mycelial cultures of the Ascomycete Bulgaria inquinans (Fr.)[J]. Nature Product Letter, 1995, 7: 7-14
[28] 杨晓静，张泓嵬，孙红，等．胶陀螺的抗肿瘤作用[J]．特产研究，1993，2：9-11
[29] 杨晓静，张树臣，高桂琴，等．胶陀螺对血瘀动物血液流变学的影响[J]．中草药，1996，27(6)：358-359
[30] 王庭欣，秦淑贞，刘燕丽．胶陀螺菌复合制剂抗突变作用的实验研究[J]．中华临床与卫生，2004，3(4)：239-240
[31] 陈明，陈立国，汪国莲．银耳极性测定的初步研究[J]．华中农业大学学报，2000，19(2)：138-141
[32] 胡梅，侯军，胡公洛．草菇组织分离法的改良[J]．食用菌，2001，2：14
[33] 吴志红，汪天虹，黄卫，等．简便易行的丝状真菌染色体DNA提取法[J]．菌物系统，2001，20(4)：575-577．
[34] 李家实．中药鉴定学[M]．上海科学技术出版社，1996，第1版：28-44
[35] 刘淑艳，李玉，白秀娟．一种提取黏菌DNA的新方法[J]．吉林农业大学学报，2001，23(2)：38-40．
[36] 金冬雁，黎孟枫．分子克隆试验指南[M]．北京：科学出版社，1995，第2版：19-56，924-929．
[37] Fenwick GA. A Conidial Form of Bulgaria inquinans[J]. Mycologist, 1992, 6(4): 177-179.
[38] 高锦明．植物化学[M]．北京：科学出版社，2003，第1版：35-37
[39] 肖崇厚．中药化学[M]．上海科学技术出版社，1997，第1版：192-220
[40] 徐叔云，卞如濂，陈修．药理实验方法学[M]．北京：人民卫生出版社，2005．第3版：179-180，195-223
[41] 陈奇．中药药理研究方法学[M]．北京：人民卫生出版社，1996．第1版：37-54，106-108
[42] 王耐勤．血卟啉新分离物—HPS光敏效应的实验研究[J]．肿瘤，1985，5(2)：49