1型糖尿病鼠类模型的肠道菌群分析

被引：0

作者：

徐灵筠

机构：

[1] 上海交通大学

关键词：

肠道菌群; 1型糖尿病; 链脲佐菌素(STZ); 乳杆菌; 双歧杆菌; 益生菌; ERIC-PCR; PCR-DGGE; PCA; PLS-DA;

D O I：

暂无

年度学位：

2007

学位类型：

硕士

导师：

赵立平;

摘要：

近年来,1型糖尿病及其动物模型的发病机理已经研究得较为透彻,鼠类模型的发病过程被归纳为遗传缺陷主导,环境因素诱发,两者相互作用导致了1型糖尿病的发生。环境因素的研究主要集中于营养物和病毒感染,肠道微生态系统因其内在复杂性而少有涉及。少数相关的文献用分离培养的方法揭示了糖尿病病人和模型动物发生了肠道菌群失调。我们实验室采用分子生态学的方法来研究两者的关系,发现肠道菌群与糖尿病的发生发展存在一定的关系,某些菌可能与糖尿病直接相关。实验中,我们将同一批ICR小鼠,随机分成两组,一组为糖尿病模型组,另外一组为健康对照组。糖尿病造模采用静脉注射链脲佐菌素(STZ)方法,造模后糖尿病小鼠体重明显轻于对照小鼠,表现出显著糖尿病“三多一少”的症状。保留几只血糖未升高的造模鼠,与造模成功小鼠的作对照。首先采用ERIC-PCR指纹图谱技术解析各组小鼠的粪便菌群总DNA样品,获得DNA指纹信息,通过PLS-DA(偏最小二乘法区别分析)统计方法寻找各组样品之间的规律性变化,结果发现,对STZ敏感的糖尿病小鼠和对STZ不敏感的小鼠的肠道菌群显著区别于健康对照小鼠的菌群,而STZ易感性小鼠与STZ抵抗型小鼠的菌群仍有一定差别。为了进一步辨别菌群结构的差异和决定此差异的菌种,我们又采用了16S rDNA V3-DGGE方法对样品进行了分析,结果显示,所有空白对照与造模不成功的鼠(统称低血糖组)都有两条较亮的条带,而糖尿病小鼠则较暗。割胶回收DNA,测序结果表明这两种

引用

页数：105

共 40 条

[1]

Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? [J].

Brugman, S. ;

Klatter, F. A. ;

Visser, J. T. J. ;

Wildeboer-Veloo, A. C. M. ;

Harmsen, H. J. M. ;

Rozing, J. ;

Bos, N. A. .

DIABETOLOGIA, 2006, 49 (09) :2105-2108

[2]

CTLA4 is differentially associated with autoimmune diseases in the Dutch population [J].

Zhernakova, A ;

Eerligh, P ;

Barrera, P ;

Weseloy, JZ ;

Huizinga, TWJ ;

Roep, BO ;

Wijmenga, C ;

Koeleman, BPC .

HUMAN GENETICS, 2005, 118 (01) :58-66

[3]

Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse [J].

Calcinaro, F ;

Dionisi, S ;

Marinaro, M ;

Candeloro, P ;

Bonato, V ;

Marzotti, S ;

Corneli, RB ;

Ferretti, E ;

Gulino, A ;

Grasso, F ;

De Simone, C ;

Di Mario, U ;

Falorni, A ;

Boirivant, M ;

Dotta, F .

DIABETOLOGIA, 2005, 48 (08) :1565-1575

[4]

Lactobacillus fermentum, a probiotic capable to release glutathione, prevents colonic inflammation in the TNBS model of rat colitis [J].

Peran, Laura ;

Camuesco, Desiree ;

Comalada, Monica ;

Nieto, Ana ;

Concha, Angel ;

Adrio, Jose Luis ;

Olivares, Monica ;

Xaus, Jordi ;

Zarzuelo, Antonio ;

Galvez, Julio .

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2006, 21 (08) :737-746

[5]

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice [J].

Giulietti, A ;

Gysemans, C ;

Stoffels, K ;

van Etten, E ;

Decallonne, B ;

Overbergh, L ;

Bouillon, R ;

Mathieu, C .

DIABETOLOGIA, 2004, 47 (03) :451-462

[6]

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes -: indication of an increased environmental pressure? [J].

Hermann, R ;

Knip, M ;

Veijola, R ;

Simell, O ;

Laine, AP ;

Åkerblom, HK ;

Groop, PH ;

Forsblom, C ;

Pettersson-Fernholm, K ;

Ilonen, J .

DIABETOLOGIA, 2003, 46 (03) :420-425

[7]

The Intestinal LABs.[J].Elaine E. Vaughan;Maaike C. de Vries;Erwin G. Zoetendal;Kaouther Ben-Amor;Antoon D.L. Akkermans;Willem M. de Vos.Antonie van Leeuwenhoek.2002, 1

[8]

Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients [J].