角叉菜的化学组成及其抗肿瘤活性的研究
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摘要
角叉菜，属红藻门，杉藻科，角叉菜属，自然分布于大西洋沿岸和我国东南
沿海以及青岛、大连等海域，是中国的一种重要经济海藻。角叉菜不仅是卡拉胶
生产的重要原藻，而且近年来越来越多地应用于医药领域，引起人们的广泛关注。
本文对采集于青岛太平角的皱波角叉菜的化学组成进行了较全面系统的分
析。角叉菜中蛋白质和多糖含量高，脂肪含量低，还含有大量的人体所必须的微
量元素，角叉菜中氨基酸含量很高，而且多是结合氨基酸。另外，为了探讨角叉
菜的活性成分，采用 GC-MS 法分析了角叉菜的乙醇提取物和氯仿-甲醇提取物的
化学组成。
本文在实验室分析方法的基础上，对其提取、分级条件进行了优化，确定了
制备方法；并首次采用密闭微波法对获得的角叉菜λ-卡拉胶进行降解，获得五
个不同分子量的降解产物，并对降解产物进行了红外、紫外和核磁共振分析，确
定了降解产物的结构和分子量范围。
本文在第四章和第五章分别研究了五个不同分子量的角叉菜λ-卡拉胶的体
内抗肿瘤活性和对化疗药物的抗肿瘤活性的影响，并测定了各组实验小鼠的多种
免疫指标。证实了角叉菜λ-卡拉胶显著的体内抗肿瘤活性和免疫调节活性,同时
能增强化疗药物的抗肿瘤能力，并有效抵抗其导致的免疫功能低下。
为探讨角叉菜λ-卡拉胶的抗肿瘤和免疫增强活性机理。本文（1）采用化学
比色法研究了角叉菜λ-卡拉胶的体外抗氧化活性，证明角叉菜λ-卡拉胶具有显
著的抗氧化活性，尤其是对小鼠肝匀浆脂质过氧化的抑制作用非常显著。（2）采
用 MTT 法研究了角叉菜λ-卡拉胶体外对脾细胞活性的影响。角叉菜λ-卡拉胶
能显著提高大鼠脾细胞自发增殖活性和刀豆蛋白（ConA）诱导的脾细胞增殖，
对紫外线所致脾细胞损伤有很好的修复作用。其对免疫细胞的修复作用很可能与
其显著的抗氧化活性有关。（3）采用 MTT 法研究了不同浓度的角叉菜λ-卡拉胶
体外对白血病 YAC-1, 宫颈癌 HeLa 和肝癌 H-7402 细胞，以及小鼠腹水传代的肝
癌 H-22 和肉瘤 S180 的体外抑制作用进行了研究，结果表明，不同分子量的角叉
菜λ-卡拉胶在一定浓度下对各种肿瘤细胞均有一定的体外抑制活性。（4）采用
鸡胚新生血管模型初步研究了角叉菜λ-卡拉胶对肿瘤新生血管生长的没有明显
的抑制作用，证实了其抗肿瘤机理并非通过抑制新生血管生长来实现。
因此，不同分子量的角叉菜λ-卡拉胶具有显著的体内抗肿瘤活性，并能提
高化疗药物的抗肿瘤效果，有效抵抗化疗药物引起的免疫功能低下。其抗肿瘤机
理是通过其自身对肿瘤细胞的杀伤作用和提高机体的免疫系统功能来实现的，而
提高机体免疫系统功能很可能与其显著的抗氧化活性有关。
Chondrus ocellatus, distributes naturally in intertidal zone of Atlantic coasts,
Chinese southeast, Qingdao and Dalian coast areas. Chondrus ocellatus was not only
an important economic alga that can produce carrageenan, but also used as a medicine
to cure chronic constipation and bone fracture in recent years. It was an important
economically valuable alga in China and has lead to more and more attention. In this
dissertation, we analyzed the chemical compositions of Chondrus ocellatus collected
on the seaside of Taiping Cape in Qingdao, optimized the procedure of the extraction,
fraction and microwave degradation of λ–carrageenan from Chondrus ocellatus. The
bioactivities in vitro and in vivo were also studied.
The basic chemical constituents and amino acid in Chondrus ocellatus were
analyzed. It is high in protein and carbohydrates but low in fat. Chondrus ocellatus
contains many essential elements of which the human body is composed of. It also
contains significant amounts of amino acid, most of them are complex amino acid. In
addition, to study the bioactive chemical constituents in Chondrus ocellatus, the
chemical components in the bioactivities of Chondrus ocellatus were extracted by
ethanol and chloroform-methanol, respectively, and were analyzed by GC-MS
Spectrometry.
At present, because of the limitation of its own characteristics, there is not high
scale industry production of λ-carrageenans. In this paper, λ-carrageenan from
Chondrus ocellatus was studied about extraction and fraction methods on the base of
their analysis method. The optimum extraction procedure of λ-carrageenan was
determined. The airtight microwave method was first used on the degradation of
λ-carrageenan from Chondrus ocellatus, and obtained five products that have different
molecular weight. IR, UV and NMR spectrum analytical results confirmed chemical
components and structure of the degraded polysaccharides.
In order to study bioactivities and effect of molecular weight on the activities of
λ-carrageenan, antitumor activities and the effect of λ-carrageenan on antitumor
ability of 5-Fu were investigated. The results of several immune targets indicated that
the five λ-carrageenans all showed anti-tumor and immunomodulation activities in
2
博士论文 角叉菜的化学组成和抗肿瘤活性
different degree and could enhance anti-tumor activities of 5-Fu and improve
immunocompetence damaged by 5-Fu.
In order to study the mechanism of antitumor and immunomodulation activities
of different molecular weight λ-carrageenans, several experiments in vivo were
investigated on chapter 6, 7, 8 and 9.
(1) The in vitro antioxidant activities of λ-carrageenan from Chondrus ocellatus
were investigated by chemical spectrometric methods. λ-Carrageenan with different
molecular weight showed antioxidant activities, especially high scavenging activities
lipid peroxide of rat liver homogenate. Molecular weight of polysaccharides had
notably effect on their antioxidant activities.
(2) The immunoregulatory effects of different molecular weight λ-carrageenans
on spleen cells were evaluated by MTT tetrazolium assay. The λ-carrageenans can
notably enhance lymphocyte proliferation spontaneously and induced by ConA. They
also can repair the injured spleen cells by ultraviolet ray. The functions may relevant
to the notable antioxidant ability of the polysaccharides
(3) The in vivo growth-inhibition of YAC-1, HeLa, H-7402 cells maintained in
vivo and H-22, S180 cells maintained in the peritoneal cavities of mice were evaluated by MTT
tetrazolium assay. The results indicated that the λ-carrageenans from Chondrus
ocellatus with some concentration have antitumor activities in vivo.
(4) The preliminary study on the effect of λ-carrageenans on angiogenesis in the
chick embryo CAMS were investigated, and they had no notable inhibitory effect.
This confirmed that an
沿海以及青岛、大连等海域，是中国的一种重要经济海藻。角叉菜不仅是卡拉胶
生产的重要原藻，而且近年来越来越多地应用于医药领域，引起人们的广泛关注。
本文对采集于青岛太平角的皱波角叉菜的化学组成进行了较全面系统的分
析。角叉菜中蛋白质和多糖含量高，脂肪含量低，还含有大量的人体所必须的微
量元素，角叉菜中氨基酸含量很高，而且多是结合氨基酸。另外，为了探讨角叉
菜的活性成分，采用 GC-MS 法分析了角叉菜的乙醇提取物和氯仿-甲醇提取物的
化学组成。
本文在实验室分析方法的基础上，对其提取、分级条件进行了优化，确定了
制备方法；并首次采用密闭微波法对获得的角叉菜λ-卡拉胶进行降解，获得五
个不同分子量的降解产物，并对降解产物进行了红外、紫外和核磁共振分析，确
定了降解产物的结构和分子量范围。
本文在第四章和第五章分别研究了五个不同分子量的角叉菜λ-卡拉胶的体
内抗肿瘤活性和对化疗药物的抗肿瘤活性的影响，并测定了各组实验小鼠的多种
免疫指标。证实了角叉菜λ-卡拉胶显著的体内抗肿瘤活性和免疫调节活性,同时
能增强化疗药物的抗肿瘤能力，并有效抵抗其导致的免疫功能低下。
为探讨角叉菜λ-卡拉胶的抗肿瘤和免疫增强活性机理。本文（1）采用化学
比色法研究了角叉菜λ-卡拉胶的体外抗氧化活性，证明角叉菜λ-卡拉胶具有显
著的抗氧化活性，尤其是对小鼠肝匀浆脂质过氧化的抑制作用非常显著。（2）采
用 MTT 法研究了角叉菜λ-卡拉胶体外对脾细胞活性的影响。角叉菜λ-卡拉胶
能显著提高大鼠脾细胞自发增殖活性和刀豆蛋白（ConA）诱导的脾细胞增殖，
对紫外线所致脾细胞损伤有很好的修复作用。其对免疫细胞的修复作用很可能与
其显著的抗氧化活性有关。（3）采用 MTT 法研究了不同浓度的角叉菜λ-卡拉胶
体外对白血病 YAC-1, 宫颈癌 HeLa 和肝癌 H-7402 细胞，以及小鼠腹水传代的肝
癌 H-22 和肉瘤 S180 的体外抑制作用进行了研究，结果表明，不同分子量的角叉
菜λ-卡拉胶在一定浓度下对各种肿瘤细胞均有一定的体外抑制活性。（4）采用
鸡胚新生血管模型初步研究了角叉菜λ-卡拉胶对肿瘤新生血管生长的没有明显
的抑制作用，证实了其抗肿瘤机理并非通过抑制新生血管生长来实现。
因此，不同分子量的角叉菜λ-卡拉胶具有显著的体内抗肿瘤活性，并能提
高化疗药物的抗肿瘤效果，有效抵抗化疗药物引起的免疫功能低下。其抗肿瘤机
理是通过其自身对肿瘤细胞的杀伤作用和提高机体的免疫系统功能来实现的，而
提高机体免疫系统功能很可能与其显著的抗氧化活性有关。
Chondrus ocellatus, distributes naturally in intertidal zone of Atlantic coasts,
Chinese southeast, Qingdao and Dalian coast areas. Chondrus ocellatus was not only
an important economic alga that can produce carrageenan, but also used as a medicine
to cure chronic constipation and bone fracture in recent years. It was an important
economically valuable alga in China and has lead to more and more attention. In this
dissertation, we analyzed the chemical compositions of Chondrus ocellatus collected
on the seaside of Taiping Cape in Qingdao, optimized the procedure of the extraction,
fraction and microwave degradation of λ–carrageenan from Chondrus ocellatus. The
bioactivities in vitro and in vivo were also studied.
The basic chemical constituents and amino acid in Chondrus ocellatus were
analyzed. It is high in protein and carbohydrates but low in fat. Chondrus ocellatus
contains many essential elements of which the human body is composed of. It also
contains significant amounts of amino acid, most of them are complex amino acid. In
addition, to study the bioactive chemical constituents in Chondrus ocellatus, the
chemical components in the bioactivities of Chondrus ocellatus were extracted by
ethanol and chloroform-methanol, respectively, and were analyzed by GC-MS
Spectrometry.
At present, because of the limitation of its own characteristics, there is not high
scale industry production of λ-carrageenans. In this paper, λ-carrageenan from
Chondrus ocellatus was studied about extraction and fraction methods on the base of
their analysis method. The optimum extraction procedure of λ-carrageenan was
determined. The airtight microwave method was first used on the degradation of
λ-carrageenan from Chondrus ocellatus, and obtained five products that have different
molecular weight. IR, UV and NMR spectrum analytical results confirmed chemical
components and structure of the degraded polysaccharides.
In order to study bioactivities and effect of molecular weight on the activities of
λ-carrageenan, antitumor activities and the effect of λ-carrageenan on antitumor
ability of 5-Fu were investigated. The results of several immune targets indicated that
the five λ-carrageenans all showed anti-tumor and immunomodulation activities in
2
博士论文 角叉菜的化学组成和抗肿瘤活性
different degree and could enhance anti-tumor activities of 5-Fu and improve
immunocompetence damaged by 5-Fu.
In order to study the mechanism of antitumor and immunomodulation activities
of different molecular weight λ-carrageenans, several experiments in vivo were
investigated on chapter 6, 7, 8 and 9.
(1) The in vitro antioxidant activities of λ-carrageenan from Chondrus ocellatus
were investigated by chemical spectrometric methods. λ-Carrageenan with different
molecular weight showed antioxidant activities, especially high scavenging activities
lipid peroxide of rat liver homogenate. Molecular weight of polysaccharides had
notably effect on their antioxidant activities.
(2) The immunoregulatory effects of different molecular weight λ-carrageenans
on spleen cells were evaluated by MTT tetrazolium assay. The λ-carrageenans can
notably enhance lymphocyte proliferation spontaneously and induced by ConA. They
also can repair the injured spleen cells by ultraviolet ray. The functions may relevant
to the notable antioxidant ability of the polysaccharides
(3) The in vivo growth-inhibition of YAC-1, HeLa, H-7402 cells maintained in
vivo and H-22, S180 cells maintained in the peritoneal cavities of mice were evaluated by MTT
tetrazolium assay. The results indicated that the λ-carrageenans from Chondrus
ocellatus with some concentration have antitumor activities in vivo.
(4) The preliminary study on the effect of λ-carrageenans on angiogenesis in the
chick embryo CAMS were investigated, and they had no notable inhibitory effect.
This confirmed that an
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发 表 文 章 目 录
已发表或已接受文章：
1、Gefei Zhou, YuePing Sun, Hua Xin, Yuna Zhang, Zhien Li, Zuhong Xu. In vivo
Anti-tumor and Immunomodulation Activities of Different Molecular Weight Lambda
–Carrageenans from Chondrus Ocellatus. Pharmacological Research, 2004, 50（1），
47-53 （SCI）
2、Gefei Zhou, Hua Xin, Wenxu Sheng, Yueping Sun, Zhien Li, Zuhong Xu. In vivo
growth-inhibition of S180 tumor by mixture of 5-Fu and low molecular
λ-carrageenans from Chondrus ocellatus. Pharmacological Research.（已接受，SCI）
3、周革非，张全斌，刘希光，李智恩，徐祖洪. 不同分子量角叉菜 λ-卡拉胶的
抗氧化活性. 海洋与湖沼，（已接受，待发表）
3、周革非, 徐坤, 赵增芹, 李智恩, 徐祖洪. GC-MS 联用法分析角叉菜中的化学
成分. 中国海洋药物，（已接受，待发表）
5、Quanbin Zhang, Ning Li, Gefei Zhou, Xiaolan Lu, Zuhong Xu, Zhien Li. In vivo
antioxidant activities of polysaccharide fraction from Porphyra haitanensis
(Rhodophyta) in aging mice. Pharmacological Research，2003, 48(2): 151-155
（SCI）
6 、 Zhang Quan-bin, Li Zhi-en, Zhou Ge-gei, Niu Xi-zhen, Zhang Hong.
Immunosuppressive activity of fucoidan from Laminaria japonica. Chinese Journal
of Oceanology and Liminology, 2003, 21(4): 324-328
7、张全斌, 于鹏展, 周革非, 李智恩, 徐祖洪. 海带褐藻多糖硫酸酯抗氧化活性
的研究. 中草药, 2003, (9)
8、周革非, 王宙清, 杨庭华.N－正辛基己内酰胺萃取铁和盐酸的机理. 有色金属,
2002, 54(3): 39-40
9、Yu Pengzhan, Li Ning, LiuXiguang, Zhou Gefei, Zhang Quanbin, Li Pengcheng.
Antihyperlipidemic effects of different molecular weight sulfated polysaccharides from
Ulva pertusa(Chlorophyta). Pharmacological Research, 2003, 48, 543-549
10、刘希光，史美丽，周革非，董士刚. 5-羟亚氨基-5-脱氧阿维霉菌素 B1 的合成
及杀虫活性研究. 莱阳农学院学报 2003,20(1)
已投稿文章：
11、周革非, 赵增芹, 李智恩, 徐祖洪. 自由基理论在致癌、防癌和抗癌中的应
用. 中国药科大学学报, (投稿中)
12、周革非, 辛华, 李智恩, 徐祖洪. 红藻角叉菜的化学组成和药用功能研究现状.
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发 表 文 章 目 录
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