仿刺参胶原蛋白多肽对Ⅱ型糖尿病小鼠肾脏的保护机制
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摘要
目的:研究仿刺参胶原蛋白多肽对db/db糖尿病小鼠的保护机制。方法:通过仿刺参多肽分组喂养糖尿病小鼠,测定小鼠血清中TC、TG、LDL-C和HDL-C含量及胰岛素浓度。采用双向电泳研究小鼠的肾脏蛋白,通过差异蛋白筛选,GO功能注释,代谢通路等分析确定仿刺参多肽对糖尿病小鼠肾脏的保护机制。生化指标显示:仿刺参多肽可以降低血清中TC、TG、LDL-C的含量和胰岛素浓度,提高HDL-C水平。双向结果表明:相对于模型组,试验组共检测出上调蛋白81个,下调蛋白51个。GO结果显示:差异蛋白的功能主要集中在蛋白转运和信号传导过程。KEGG分析发现,差异蛋白主要富集在代谢途径、胰岛素抵抗和胰岛素信号传导过程。结论:喂养仿刺参多肽的小鼠体内视黄醇结合蛋白4的表达下调,血糖水平下降,胰岛素信号通路恢复正常,可以有效缓解糖尿病的症状。
The purpose of this paper is to study the protection mechanism of Apostichopus joponicus polypeptide to Ⅱ diabetic mouse(db/db diabetic mouse) kidney. By animal experiments, db/db mice are fed in different groups. Then determinati the content of TC, TG, LDL-C, HDL-C and insulin concentration in mouse serum. The regulation of db/db diabetic mouse kidney is studied by two-dimensional electrophoresis. Then detecting differential proteins of db/db mice kidneys, differential protein expression, GO functional analysis and KEGG pathway analysis. Apostichopus joponicus polypeptide can reduce the levels of serum TC, TG, LDL and insulin concentration, increased HDL-C levels in diabetic mouse. Two-dimensional electrophoresis results showed that compared with the model group, the number of up-regulated protein is 81, and down-regulated protein is 51 in the experimental group. GO results showed that the function of the differential protein mainly focused on protein transport and signal transduction. KEGG analysis revealed that the differential proteins were mainly enriched in metabolic pathways, insulin resistance and insulin signaling processes. The expression of retinol-binding protein 4 in mice fed with polypeptides was reduced, the blood glucose level was decreased, and the insulin signal pathway returned to normal, which could relieve the symptoms of diabetes mellitus.
The purpose of this paper is to study the protection mechanism of Apostichopus joponicus polypeptide to Ⅱ diabetic mouse(db/db diabetic mouse) kidney. By animal experiments, db/db mice are fed in different groups. Then determinati the content of TC, TG, LDL-C, HDL-C and insulin concentration in mouse serum. The regulation of db/db diabetic mouse kidney is studied by two-dimensional electrophoresis. Then detecting differential proteins of db/db mice kidneys, differential protein expression, GO functional analysis and KEGG pathway analysis. Apostichopus joponicus polypeptide can reduce the levels of serum TC, TG, LDL and insulin concentration, increased HDL-C levels in diabetic mouse. Two-dimensional electrophoresis results showed that compared with the model group, the number of up-regulated protein is 81, and down-regulated protein is 51 in the experimental group. GO results showed that the function of the differential protein mainly focused on protein transport and signal transduction. KEGG analysis revealed that the differential proteins were mainly enriched in metabolic pathways, insulin resistance and insulin signaling processes. The expression of retinol-binding protein 4 in mice fed with polypeptides was reduced, the blood glucose level was decreased, and the insulin signal pathway returned to normal, which could relieve the symptoms of diabetes mellitus.
引文
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[19]TOYE A A, LEE M, ALISON H, et al. A new mouse model of type 2 diabetes, produced by NEthyl-Nitrosourea mutagenesis, is the result of a missense mutation in the glucokinase gene[J]. Diabetes, 2004, 53(6):1577-1583.
[20]谢利芳,许志华,郭凯霞. 2型糖尿病胰岛素抵抗研究进展[J].科学技术与工程, 2010, 10(15):3664-3669.
[21]RITZ E, BERGIS K, FLISER D. The metabolic syndrome[J]. Medical Clinics of North America, 1995,88(4):181-183.
[22]程灿,赵芳芳,王季猛.视黄醇结合蛋白4与2型糖尿病微血管病变的研究进展[J].现代生物医学进展, 2011, 11(2):384-386.
[23]梁琳琅,张杰,周文平,等.代谢综合征患者血清视黄醇结合蛋白4的变化及其影响因素[J].中国实用内科杂志, 2008, 28(4):267-270.
[24]CHOI S, KWAK S B, LIM S, et al. High plasma retinol binding protein-4 and low plasma adiponectin concentrations are associated with severity of glucose intolerance in women with previous gestational diabetes mellitus[J]. Journal of Clinical Endocrinology&Metabolism, 2008, 93(8):3142-3148.
[25]FREY S K, NAGL B, HENZE A, et al. Isoforms of Retinol binding protein 4(RBP4)are increased in chronic diseases of the kidney but not of the liver[J]. Lipids in Health&Disease, 2007, 7(1):1-9.
[26]蒋礼,张玲.视黄醇结合蛋白测定在肾脏疾病中的研究进展[J].国外医学(泌尿系统分册), 2003, 23(5):597-599.
[27]汪明东,孙立山,郑慧雅,等.血清视黄醇结合蛋白对评价早期肾损伤的诊断价值[J].国际检验医学杂志, 2011, 32(21):2448-2449.
[2]向怡卉,苏秀榕,董明敏.海参体壁及消化道的氨基酸和脂肪酸分析[J].水产科学, 2006, 25(6):280-282.
[3]苏秀榕,娄永江,常亚青,等.海参的营养成分及海参多糖的抗肿瘤活性的研究[J].营养学报, 2003,25(2):181-182.
[4]苏秀榕,向怡卉,郑卫星,等.刺参消化道多糖的研究[C]//2007年全国生化与生物技术药物学术年会论文集.济南:中国药学会, 2007.
[5]张悦容,刘文,夏长革,等.南北人工养殖仿刺参挥发性物质的比较研究[J].中国食品学报, 2013,13(10):222-230.
[6]侯付景,李妍妍,金春华,等.白肛海地瓜和刺参体壁的比较分析[J].食品科学, 2010, 31(11):38-41.
[7]穆琳,赵晓玥,高岳,等.刺参多糖的提取纯化及其组分的分析[J].食品安全质量检测学报, 2016, 7(1):314-321.
[8]吕晶晶,王彩霞,魏娜,等.自发性2型糖尿病小鼠db/db的生物学特性[J].沈阳药科大学学报,2013, 30(6):455-459.
[9]蒋鑫,徐静,李妍妍,等.海参消化道多糖降血脂功能的研究[J].中国食品学报, 2011, 11(7):46-49.
[10]王霞,李妍妍,苏秀榕,等.金枪鱼胰脏酶解液对糖尿病大鼠血糖和血脂的作用[J].中国食品学报,2012, 12(7):24-28.
[11]麻仕利,王伟,梁蓉.同型半胱氨酸代谢关键酶基因多态性与单纯收缩期高血压关系的初步研究[J].天津医科大学学报, 2016, 22(2):93-96.
[12]于荣敏,严春艳,曲红艳,等.近年来海洋生物活性多肽的研究概况与展望[J].海洋通报, 2004, 23(3):87-93.
[13]王志远,李霞,王斌,等.仿刺参肠多糖对免疫功能的影响及抗肿瘤研究[J].农业生物技术学报,2012, 20(5):560-567.
[14]刘雪峰,李磊,闫文亮,等.杏仁多肽的降血糖活性研究[J].内蒙古农业大学学报(自然科学版),2010, 31(2):204-208.
[15]徐军,吴鹏,韩琳,等.苦瓜中植物降糖多肽的分离及其降糖作用的研究[J].中国医药导报, 2007, 2(4):148-150.
[16]王茵,吴靖娜,苏捷,等.鱼皮胶原多肽的降血压效果研究[J].中国海洋药物, 2014, 33(2):39-44.
[17]顾伟,徐永健.大海马ACE抑制肽制备及其抗氧化能力的测定[J].食品工业科技, 2016, 37(5):201-211.
[18]KASETTI R B, RAJASEKHAR M D, KONDETI V K, et al. Antihyperglycemic and antihyperlipidemic activities of methanol:water(4∶1)fraction isolated from aqueous extract of Syzygium alternifolium seeds in streptozotocin induced diabetic rats[J]. Food and Chemical Toxicology, 2010, 48(4):1078-1084.
[19]TOYE A A, LEE M, ALISON H, et al. A new mouse model of type 2 diabetes, produced by NEthyl-Nitrosourea mutagenesis, is the result of a missense mutation in the glucokinase gene[J]. Diabetes, 2004, 53(6):1577-1583.
[20]谢利芳,许志华,郭凯霞. 2型糖尿病胰岛素抵抗研究进展[J].科学技术与工程, 2010, 10(15):3664-3669.
[21]RITZ E, BERGIS K, FLISER D. The metabolic syndrome[J]. Medical Clinics of North America, 1995,88(4):181-183.
[22]程灿,赵芳芳,王季猛.视黄醇结合蛋白4与2型糖尿病微血管病变的研究进展[J].现代生物医学进展, 2011, 11(2):384-386.
[23]梁琳琅,张杰,周文平,等.代谢综合征患者血清视黄醇结合蛋白4的变化及其影响因素[J].中国实用内科杂志, 2008, 28(4):267-270.
[24]CHOI S, KWAK S B, LIM S, et al. High plasma retinol binding protein-4 and low plasma adiponectin concentrations are associated with severity of glucose intolerance in women with previous gestational diabetes mellitus[J]. Journal of Clinical Endocrinology&Metabolism, 2008, 93(8):3142-3148.
[25]FREY S K, NAGL B, HENZE A, et al. Isoforms of Retinol binding protein 4(RBP4)are increased in chronic diseases of the kidney but not of the liver[J]. Lipids in Health&Disease, 2007, 7(1):1-9.
[26]蒋礼,张玲.视黄醇结合蛋白测定在肾脏疾病中的研究进展[J].国外医学(泌尿系统分册), 2003, 23(5):597-599.
[27]汪明东,孙立山,郑慧雅,等.血清视黄醇结合蛋白对评价早期肾损伤的诊断价值[J].国际检验医学杂志, 2011, 32(21):2448-2449.