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沙棘叶科罗索酸浓缩物的毒理学和人群试验

Toxicology and Crowed Test on Corosolic Acid Concentrations of Seabuckthorn Leaves

【作者】 王斌

【导师】 张小民;

【作者基本信息】 山西大学 , 动物学, 2017, 硕士

【摘要】 随着人民生活水平的提高以及生活方式的改变,越来越多的人饮食无规律以及缺乏运动,导致每天摄入到体内的能量无法及时排出体外,长时间就会引起机体血脂和血糖升高。近年来,每年我国糖尿病患病率逐渐升高,被列为三大疾病之一。沙棘里含有大量的生物活性物质且具有较强的保健功效,因此也被称为“神果”。科罗索酸,一种三萜类化合物,已经被证明具有降血糖降血脂作用,而实验室先前已从沙棘叶中提取到科罗索酸物质,为了证明沙棘叶中科罗索酸有无毒性以及对人是否有降血糖作用,本研究按照食品安全性毒理学评价程序和方法对沙棘叶科罗索酸浓缩物进行了小鼠急性经口毒性试验,小鼠骨髓细胞微核试验和小鼠精子畸形试验;同时以实验室现有的沙棘叶科罗索酸浓缩物为主要成分制作缓释胶囊,供于Ⅱ型糖尿病患者,使其按照一日三次一次四粒方法食用,分别检测试食前、试食一个月以及试食两个月后的空腹血糖含量、糖化血红蛋白、血清胆固醇、血清甘油三酯、空腹C肽释放量和空腹胰岛素释放量六项指标以及观察血细胞形态和结构的变化。主要实验结果如下:1、小鼠急性经口毒性试验结果表明,沙棘叶浓缩物对雌雄小鼠经口最大耐受剂量(MTD)均大于15g/kg·bw,为无毒级物质;Ames试验、小鼠骨髓细胞微核试验和小鼠精子畸形试验表明该检品对机体未造成突变;小鼠30 d喂养试验表明该小鼠的体重、进食和食物利用率不会受到该受试物明显的影响。2、沙棘叶科罗索酸浓缩物受试物人体试食实验结果显示,与试食前相比,受试人体空腹血糖含量、糖化血红蛋白、胆固醇与血清甘油三酯四项指标均表现不同程度的下降,而空腹C肽释放量和空腹胰岛素释放量出现了小幅度的升高。3、通过血细胞形态的观察发现,与试食前相比,试食后红细胞由彼此粘附状态恢复至正常红细胞状态,中性粒细胞轮廓模糊,分叶增多及淋巴细胞和单核细胞结构变形、受损等现象也有所改变。综上,实验结果表明沙棘叶科罗索酸浓缩物无毒性且初步证明该受试物对人体有降血糖作用。这不仅为沙棘叶浓缩物可食性提供理论依据,也会对整个沙棘叶的开发以及糖尿病的治疗起到积极的推动作用。

【Abstract】 With the living standard promoted and lifestyle changed,an increasing number of people have an irregular diret and little excrise,which lead to the consequence that energy in body can’t discharged timely.As a result,blood liquid and blood glucos level increase.In recent years,with growing prevalence rate,diabetes has been regarded as one of the three major diseases.Seabuckthorns knowen as ′shenguo′ contain a large number of bioactive substances and have higher healthy functions.Cosolic acids,a kind of triterpene compounds,have been turned out that they have hypoglycemic and hypolipidemic effects,and they have been extracted from seabuckthorn leaves in our laboratory previously.In order to prove the nontoxicity and hypoglycemic activity of the cosolic acid in seabuckthorn leaves,the acute oral toxicity,micronucleus test of bone marrow and sperm shape abnormality test in mice was applid on corosolic acid concentrations in seabuckthorn leaves according to the evaluation processes and methods of food safety toxicology.At the same time,we made sustained-release capsules containing the main ingredient of colorado acid in seabuckthorn leaves and provided them for type 2 diabetes patients.They eat them three times a day and four tablets one time,and then we tested fasting blood glucose,glycosylated hemoglobin,cholesterol,triglyceride,fasting C peptide release,fasting insulin release before eating the specimen,eating for one month and eating for two months.Meanwhile,we observed the morphological and structural changes in blood cells.The main results were as follows:1.The acute oral toxicity showed the maximum tolerated dosesea(MTD)of buckthorn leaves concentrations throμgh the mouth of mice was greater than 15g/kg,indicating the buckthorn leaves concentrations had no toxic;the Ames test,micronucleus test and sperm shape abnormality test demonstrated that the examined sample didn’t presented mutagennicity.Besides,the 30 d feeding test have no effect on the weight,food instake and food utility in mice.2.Human experiments of corosolic acid concentrate samples of seabuckthorn leaves turned out that the contents of the fasting blood glucose,glycosylated hemoglobin,cholesterol,triglyceride in experimental group were decreased in different degrees and fasting C peptide release and fasting insulin release were decreased with a small drop compared to control.3.Compared with the blood cell morphology before drμg feeding tests,the red blood cells would recover from coherent condition,the situation of blurred neutrophil contour and increased leaf could be changed,as well as the malformation or damage of lymphocytes and monocytes.In conclusion,the results above indicated that the concentrate of corosolic acid in seabuckthorn leaves were nontoxic and had hypoglycemic effect for human preliminary.This study not only provided theoretical basis for edibility of seabuckthorn leaves concentrations,but promoted the exploitation of seabuckthorn leaves and the treatment of diabetes actively.

【关键词】 沙棘糖尿病科罗索酸毒理学
【Key words】 SeabuckthornDiabetesCorosolic acidToxicology
  • 【网络出版投稿人】 山西大学
  • 【网络出版年期】2018年 03期
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