文献类型：学位论文

中文题名：乌贼墨多糖的化疗保护作用研究

英文题名：Study on Protective Effects of Sepia Ink Polysaccharides on Chemotherapy

作者：王光[1];

机构：[1]广东海洋大学;

导师：钟杰平;广东海洋大学

授予学位：硕士

语种：中文

中文关键词：乌贼墨多糖;环磷酰胺;雌性生殖系统;造血系统;抗氧化能力

外文关键词：Sepia ink polysaccharides; Cyclophosphamide; Female reproductive system; Hemopoietic system; Antioxidative capacity

中文摘要：目的:环磷酰胺是目前临床上常用的氮芥类化疗药物,但其在杀伤肿瘤细胞的同时对于正常组织也具有较强的毒副作用,而使其在临床上的应用受到了一定程度的限制。乌贼墨多糖是从乌贼墨中分离提取得到的活性物质,对于乌贼墨及其中的蛋白多糖复合体和黑色素的研究前人已有诸多报道,但是鲜见关于乌贼墨多糖的活性研究报道。因此,本研究拟利用大鼠或小鼠通过腹腔注射环磷酰胺造化疗损伤模型,通过口服灌喂乌贼墨多糖,对比观察动物在化疗后同一时间上几种脏器组织内生化指标、血液学指标及病理组织学的变化情况,从而探讨乌贼墨多糖对环磷酰胺所致的卵巢、脾脏、肝、肺、肾脏、心肌化疗损伤的修复作用及其可能的作用机制,为其今后的合理开发及临床应用提供科学依据。 方法:健康的昆明种小鼠/(雌雄各半/),随机分为8组,通过检测外周血象,谷丙转氨酶活力,尿酸和胆固醇的变化对乌贼墨多糖的最佳剂量浓度进行测试,并重复测试确定最佳剂量。 40只雌性S.D.大鼠,随机分为4组:对照组,模型组,多糖组,治疗组。试验周期/(15天/)结束后,检测体重、卵巢指数、血清中激素水平、血清和卵巢中抗氧化能力及卵巢组织病理组织学变化。 40只S.D.大鼠,随机分为4组,雌雄各半,分组方式同上,试验周期结束后/(15天/),检测外周血象、脾脏指数、骨髓DNA含量、脾脏组织中抗氧化能力及病理组织学变化。 40只BALB//C小鼠,随机分为4组,雌雄各半,分组方式同上,试验周期结束后/(15天/),检测肝、肾、肺、心脏指数及四种脏器组织中抗氧化能力变化,肝组织中谷丙转氨酶和谷草转氨酶活力变化,血清中总胆红素、白蛋白、尿素氮、肌酐、尿酸和β-N-乙酰氨基葡萄糖苷酶的变化。 结果:本试验得到的乌贼墨多糖的得率约为1/%,经过几次Sevag法除蛋白后,蛋白含量仍为3.07/%,硫酸根离子含量为6.297/%,经过两次剂量浓度测试,本着浓度最低,活性最高原则,我们认为最佳剂量浓度为180mg//kg。 腹腔注射环磷酰胺后大鼠卵巢指数显著降低/(P<0.05/),卵巢组织中T-AOC显著升高/(P<0.05/),血清中T-AOC也有所升高,但差异不显著/(P>0.05/),对于不同抗氧化酶以及氧化产物含量的影响也不尽相同/(P<0.05或P>0.05/),血清中E2和P的含量显著降低/(P<0.05/),FSH含量显著升高/(P<0.01/);与对照组比较,光镜下卵巢组织中各级卵泡的数量锐减,无成熟卵泡,组织细胞大量纤维化;与模型组比较,乌贼墨多糖均能不同程度的改变由环磷酰胺所致的各项指标的变化/(P<0.05或P>0.05/) 环磷酰胺均能极其显著的降低正常大鼠外周血白细胞,红细胞,血小板,血红蛋白及骨髓中DNA变化/(P<0.01/),能显著的降低正常大鼠的脾脏指数/(P<0.05/),能代偿性的升高正常大鼠脾脏组织中SOD活力和MDA含量,但差异不显著/(P>0.05/)。乌贼墨多糖对正常大鼠的各项指标无显著影响/(P>0.05/),但能不同程度的抑制环磷酰胺所致的白细胞,血小板及骨髓DNA变化/(P<0.01或P<0.05/),对血红蛋白,红细胞具有一定的保护作用,对脾脏指数具有一定的升高作用但差异均不显著/(P>0.05/)。 乌贼墨多糖能极其显著的抑制环磷酰胺所致的小鼠肝系数、肝组织中ALT和AST的变化/(P<0.01/),但对白蛋白和总胆红素变化的影响不显著;能够极其显著的升高环磷酰胺所致的尿素氮的降低/(P<0.01/),但对尿酸,β-N-乙酰氨基葡萄糖苷酶和肌酐的影响不显著。同时,乌贼墨多糖也能不同程度的抑制环磷酰胺所致的上述脏器组织中抗氧化能力的变化。 结论:乌贼墨多糖对环磷酰胺引起的雌性生殖系统,造血系统及各种脏器损伤具有一定程度的修复作用。

外文摘要：Objective: Cyclophosphamide /(CP/) is an alkylating agent, the most commonly used anti-tumour drugs in practice, but it also has intense side effects on normal tissues when it kills the tumour cells, which lead to the limitation of CP to some extent. Sepia ink polysaccharides /(SIPS/) is a kind of active substance extracted from sepia ink, the research on sepia ink and on peptidoglycan or melanin from sepia ink has been done by the former researchers, but the paper on the activity of SIPS is seldom seen. So we created chemotherapeutic injury model by injecting with CP and administered SIPS orally on rats or mice, examined the changes of bio-chemistry parameters in some organs, blood indexes as well as histopathological changes, further explored the restorative effects of SIPS on injuries of ovary, spleen, liver, lung, kidney, heart induced by CP and it’s possible mechanisms. Our results provide the scientific evidence of reasonable exploitation and application of sepia ink. Method: Healthy Kunming mice were divided into 8 groups, male and female mice share equal quantity. Various concentrations of SIPS were administered orally to the CP intoxicated animals to optimize the maximum efficacy of SIPS in the minimum dose, determined by the changes of peripheral blood profile, Glutamic-pyruvic transaminase, DNA contents in bone marrow, and uric acid in serum, and repeated it. 40 female S.D. rats were randomly divided into 4 groups, consisting of 10 rats each: control group, model group, SIPS group and treated group, examined the changes of bodyweight, index of ovary, hormone level in serum, antioxidative capacity in blood and in ovary. 40 S.D. rats were randomly divided into 4 groups, male and female rats share equal quantity in each. The way of grouping was the same with above, determined the changes of peripheral blood profile, index of spleen, contents of DNA in bone marrow, antioxidative capacity in spleen and histopathological changes after the experiment period. 40 BALB//C mice were randomly divided into 4 groups, male and female mice share equal quantity in each. And also the way of grouping was the same with above, the changes of index of liver, kidney, lung, heart and antioxidative capacity in them, ALT and AST in liver, and total bilirubin /(TBIL/), albumin,blood urea nitrogen /(BUN/), creatinine,β-N-Acetyl-glucosaminidase /(NAG /)in blood were examined. Results: The yield of SIPS that extracted by us was about 1/%, the contents of protein is also 3.07/% after being gotten rid of protein by Sevag method, the sulfate content is 6.297/%. After twice tests, we confirmed that the optimal concentration of SIPS was 180mg//kg among various concentrations tested by us. Compared with control group, CP can change the contents of P, E2, FSH in blood and the T-AOC in ovary tissue significantly /(P<0.01 or P<0.05/), but had no obvious effects on T-AOC in serum /(P>0.05/), and it also had different effects on different kinds of enzymes in blood or organ /(P>0.05 or P<0.05/) .CP can sharply reduce the quantity of follicles in different phases, and there was not mature follicles in ovary which had focal fibrosis in histiocyte. compared with model group, SIPS can ameliorate incoordinately the changes of parameters induced by CP /(P<0.05 or P>0.05/). CP can affect significantly the contents of erythrocytes, leukocytes, hemoglobin, platelets in blood , DNA in bone marrow/(P<0.01/), organ index of spleen/(P<0.05/), as well as the contents of MDA and the activity of SOD in spleen/(P>0.05/). SIPS had no obvious effects on the above parameters compared with control group, but can incoordinately change the parameters induced by CP/(P<0.05 or P<0.01/)except for contents of erythrocytes and hemoglobin and organ index of spleen/(P>0.05/). SIPS can inhibit obviously the changes of index of liver, the activity of ALT and AST in liver , contents of BUN in blood induced by CP /(P<0.01/) , but had no effects on albumin, NAG, creatinine, uric acid level in blood. Meanwhile, SIPS also can inhibit incoordinately antioxidative capacity changes in above organs induced by CP. Conclusions: SIPS can protect female reproductive system, hemopoietic system and some organs from chemotherapeutic injuries induced by CP.

年份：2010