Ghrelin与胰岛素抵抗关系的研究及氮乙酰半胱氨酸干预作用的观察
发布时间：2018-08-05 13:51
【摘要】：目的：随着中国社会不断进步、经济日益发展,人民生活的水平得以提高,衣食住行各个方面得到了前所未有的改善,从而被查出患有2型糖尿病的人民群众愈来愈多,IDF预计到2025年全球2型糖尿病患者就达到3.88亿,近几年有关2型糖尿病的预防和治疗的研究也越来越多,尤其是某些胃肠肽类激素(如胰泌素、生长抑素、瘦素等)的研究越来越受到重视,其中由胰岛a、β、ε细胞及胃粘膜细胞等分泌的Ghrelin除具有增加食欲、促进摄食、增加胃酸分泌、促进胃肠动力等作用,另外在调节能量平衡、增加脂肪堆积也有一定作用,同时还可影响胰岛β细胞分泌胰岛素,与胰岛素抵抗有一定的相关性,而2型糖尿病的发病基础既是胰岛素抵抗的产生,因此Ghrelin与肥胖、胰岛素抵抗及2型糖尿病的发生有一定的相关性。另外,氧化应激对胰岛β细胞的损伤是产生胰岛素抵抗关键因素之一,应用抗氧化剂来减轻胰岛素抵抗、改善胰岛功能对2型糖尿病的治疗意义重大。本文通过大鼠高脂饮食诱导胰岛素抵抗动物模型,研究Ghrelin与胰岛素抵抗的关系,并观察氮乙酰半胱氨酸对Ghrelin及胰岛素抵抗的影响。方法：40只雄性SD大鼠适应性喂养1周,计算机随机分成2组：对照组A组(n=10)给予正常饮水和普通饲料(碳水化合物70%,脂肪10%,蛋白质20%)；高脂组B组(n=30)给予正常饮水和高脂饲料(碳水化合物50%,脂肪30%,蛋白质20%),共饲养12周。12周后,对B组采用内眦取血的方法进行采血测定空腹血糖和空腹胰岛素,通过对胰岛抵抗指数(HOMA-IR)进行计算,决定选用30只大鼠建立胰岛素抵抗模型。胰岛素抵抗动物模型建立成功后,将B组随机分为高脂对照组(C组,n=15)和高脂干预组(D组,n=15),继续给予A组普通饲料喂养,C组和D组高脂饲料喂养；同时给予D组氮乙酰半胱氨酸200mg/(kg·d)灌胃,给予A组和C组生理盐水灌胃,灌胃4周后采血处死大鼠,空腹血糖应用强生稳豪血糖仪测定,甘油三酯、总胆固醇、低密度脂蛋白应用全自动生化分析仪检测,空腹胰岛素和Ghrelin采用酶联免疫吸附试验(ELISA)测定。SABC免疫组织化学检测胰腺组织Ghrelin的表达。应用SPSS 13.0软件包统计分析。各参数以x±s表示,组间数据采用t检验分析,Ghrelin与糖尿病相关指标采用Pearson相关分析。P0.05认为差异有统计学意义。结果：(1)各组各项指标的变化与A组比较,C组的,FBG、FINS、TG、CHO、LDL、HOMA-IR明显升高,差异有统计学意义(P0.05);与C组比较,D组的FBG、FINS、TG、CHO、HOMA-IR明显降低,差异有统计学意义(P0.05)；D组与A组相比较无统计学意义(P0.05)；(2)各组血清Ghrelin水平的变化与A组相比,C组的Ghrelin水平明显升高,差异有统计学意义(P0.05)；与C组比较,D组的Ghrelin水平明显降低,差异有统计学意义(P0.05)；(3)相关性分析血清ghrelin水平与FBG、FINS、TG、CHO、LDL、HOMA-IR负相关(r值分别为-0.768、-0.798、-0.64、-0.708、-0.749、-0.721,P0.05)；(4)各组胰腺组织中Ghrelin的表达：与A组相比,C组的Ghrelin的表达率明显升高,差异有统计学意义(P0.05)；与C组比较,D组的Ghrelin的表达率明显降低,差异有统计学意义(P0.05)。结论：(1)高脂饲料建立胰岛素抵抗模型,造模成功率高,过程简单易行,随着胰岛素抵抗动物模型的形成,体重、空腹血糖、甘油三酯、胆固醇、低密度脂蛋白、血浆胰岛素浓度均呈递增趋势。(2)随着胰岛素抵抗动物模型的形成,血清Ghrelin的浓度呈递减趋势,且与空腹血糖、甘油三酯、胆固醇、低密度脂蛋白、血浆胰岛素浓度及胰岛素抵抗指数呈负相关,且胰腺组织中Ghrelin表达呈递减趋势,提示Ghrelin分泌的减少可能是机体调节能量平衡的反馈形式；(3)Ghrelin能够抑制胰岛素的分泌,而当血清Ghrelin及胰腺组织分泌Ghrelin的水平降低时,胰岛素分泌增加,提示低Ghrelin血症可能是发生胰岛素抵抗、2型糖尿病的独立危险因素。(4)氮乙酰半胱氨酸显著降低胰岛素抵抗动物模型的空腹血糖、甘油三酯、胆固醇、低密度脂蛋白、血浆胰岛素浓度,升高血清Ghrelin的水平,并使胰腺组织分泌Ghrelin增加,从而抑制胰岛素的分泌,改善胰岛素抵抗。
[Abstract]:Objective: with the continuous progress of the Chinese society, the economic development, the improvement of the people's living standards and the unprecedented improvement in all aspects of food and clothing and accommodation, the more and more people have been identified with type 2 diabetes. IDF is expected to reach 388 million of the world type 2 diabetic patients by 2025. In the last few years, type 2 diabetes is related to type 2 diabetes. More and more research on prevention and treatment, especially some gastrointestinal peptide hormones such as tryptin, somatostatin, leptin, and so on, has been paid more and more attention. In addition, the Ghrelin secreted by islet A, beta, epsilon and gastric mucosa cells can increase appetite, promote food intake, increase gastric acid secretion and promote gastrointestinal motility. In regulating the balance of energy and increasing the accumulation of fat, it also has a certain effect on the secretion of insulin in islet beta cells. There is a certain correlation between insulin resistance and insulin resistance. The basis of the onset of type 2 diabetes is not only the production of insulin resistance, so there is a certain correlation between Ghrelin and obesity, insulin resistance and type 2 diabetes. In addition, the damage of oxidative stress on islet beta cells is one of the key factors to produce insulin resistance. It is of great significance to use antioxidants to reduce insulin resistance and to improve islet function for type 2 diabetes. In this paper, the relationship between Ghrelin and insulin resistance was studied by using high fat diet induced insulin resistance in rats and the relationship between insulin resistance and insulin resistance was studied. The effect of nitrogen acetyl cysteine on Ghrelin and insulin resistance. Methods: 40 male SD rats were fed for 1 weeks. The computer was randomly divided into 2 groups: the control group A (n=10) was given normal drinking water and ordinary diet (carbohydrate 70%, fat 10%, protein 20%), and the high fat group B group (n=30) gave normal drinking water and high fat diet (carbon hydrate combination). 50%, fat 30%, protein 20%), after a total of 12 weeks of feeding.12 weeks, the B group used the method of inner canthus to collect blood fasting blood glucose and fasting insulin. By calculating the islet resistance index (HOMA-IR), 30 rats were chosen to establish the insulin resistance model. After the establishment of the insulin resistance animal model, the B group was randomly divided. For the high fat control group (group C, n=15) and the high fat intervention group (group D, n=15), the diet of the A group, the C group and the D group were fed, and the C group and the D group were fed with high fat diet. At the same time, the D group was given the nitrogen acetyl cysteine 200mg/ (kg. D) gavage, and the rats were given the A group and the normal saline group. After 4 weeks of gavage, the rats were killed and the fasting blood glucose was measured by Johnson glycemic glucose meter, Triglyceride, total cholesterol, low density lipoprotein were detected by automatic biochemical analyzer. Fasting insulin and Ghrelin were detected by enzyme linked immunosorbent assay (ELISA) for the expression of Ghrelin in pancreatic tissue by.SABC immunohistochemistry. The SPSS 13 software package was used for statistical analysis. The parameters were x + s, and the data between groups were analyzed by t test. The results were as follows: (1) the difference between Ghrelin and Pearson was statistically significant. (1) compared with the A group, the changes of each index were significantly higher in C group, FBG, FINS, TG, CHO, LDL, HOMA-IR. Study significance (P0.05); there was no significant difference between group D and A group (P0.05); (2) the level of serum Ghrelin in group C was significantly higher than that in A group, and the difference was statistically significant (P0.05). Compared with the C group, the Ghrelin level of D group was significantly lower, and the difference was statistically significant. (3) correlation analysis serum analysis. The negative correlation between the levels and FBG, FINS, TG, CHO, LDL, HOMA-IR (R values were -0.768, -0.798, -0.64, -0.708, -0.749, etc.); (4) the expression rate of pancreatic tissue in each group was significantly higher than that in the group. Statistical significance (P0.05). Conclusion: (1) high fat diet to establish insulin resistance model, high success rate, simple process, with the formation of insulin resistance animal model, body weight, fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentration increased trend. (2) with the insulin resistance animal model The concentration of serum Ghrelin decreased, and it was negatively correlated with fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentration and insulin resistance index, and the expression of Ghrelin in the pancreas tissue decreased, suggesting that the decrease of Ghrelin secretion may be the feedback form of regulating energy balance; (3) Ghr Elin inhibits the secretion of insulin, and increases in insulin secretion when serum Ghrelin and pancreatic tissue secrete Ghrelin levels, suggesting that low Ghrelin may be an independent risk factor for insulin resistance and type 2 diabetes. (4) N-acetylcysteine significantly reduces fasting blood glucose in insulin resistance animal models, glycerol three Ester, cholesterol, low density lipoprotein, plasma insulin concentration, increase the level of serum Ghrelin, and increase the secretion of Ghrelin in the pancreatic tissue, thus inhibiting the secretion of insulin and improving insulin resistance.
【学位授予单位】：滨州医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1
本文编号：2165988
[Abstract]:Objective: with the continuous progress of the Chinese society, the economic development, the improvement of the people's living standards and the unprecedented improvement in all aspects of food and clothing and accommodation, the more and more people have been identified with type 2 diabetes. IDF is expected to reach 388 million of the world type 2 diabetic patients by 2025. In the last few years, type 2 diabetes is related to type 2 diabetes. More and more research on prevention and treatment, especially some gastrointestinal peptide hormones such as tryptin, somatostatin, leptin, and so on, has been paid more and more attention. In addition, the Ghrelin secreted by islet A, beta, epsilon and gastric mucosa cells can increase appetite, promote food intake, increase gastric acid secretion and promote gastrointestinal motility. In regulating the balance of energy and increasing the accumulation of fat, it also has a certain effect on the secretion of insulin in islet beta cells. There is a certain correlation between insulin resistance and insulin resistance. The basis of the onset of type 2 diabetes is not only the production of insulin resistance, so there is a certain correlation between Ghrelin and obesity, insulin resistance and type 2 diabetes. In addition, the damage of oxidative stress on islet beta cells is one of the key factors to produce insulin resistance. It is of great significance to use antioxidants to reduce insulin resistance and to improve islet function for type 2 diabetes. In this paper, the relationship between Ghrelin and insulin resistance was studied by using high fat diet induced insulin resistance in rats and the relationship between insulin resistance and insulin resistance was studied. The effect of nitrogen acetyl cysteine on Ghrelin and insulin resistance. Methods: 40 male SD rats were fed for 1 weeks. The computer was randomly divided into 2 groups: the control group A (n=10) was given normal drinking water and ordinary diet (carbohydrate 70%, fat 10%, protein 20%), and the high fat group B group (n=30) gave normal drinking water and high fat diet (carbon hydrate combination). 50%, fat 30%, protein 20%), after a total of 12 weeks of feeding.12 weeks, the B group used the method of inner canthus to collect blood fasting blood glucose and fasting insulin. By calculating the islet resistance index (HOMA-IR), 30 rats were chosen to establish the insulin resistance model. After the establishment of the insulin resistance animal model, the B group was randomly divided. For the high fat control group (group C, n=15) and the high fat intervention group (group D, n=15), the diet of the A group, the C group and the D group were fed, and the C group and the D group were fed with high fat diet. At the same time, the D group was given the nitrogen acetyl cysteine 200mg/ (kg. D) gavage, and the rats were given the A group and the normal saline group. After 4 weeks of gavage, the rats were killed and the fasting blood glucose was measured by Johnson glycemic glucose meter, Triglyceride, total cholesterol, low density lipoprotein were detected by automatic biochemical analyzer. Fasting insulin and Ghrelin were detected by enzyme linked immunosorbent assay (ELISA) for the expression of Ghrelin in pancreatic tissue by.SABC immunohistochemistry. The SPSS 13 software package was used for statistical analysis. The parameters were x + s, and the data between groups were analyzed by t test. The results were as follows: (1) the difference between Ghrelin and Pearson was statistically significant. (1) compared with the A group, the changes of each index were significantly higher in C group, FBG, FINS, TG, CHO, LDL, HOMA-IR. Study significance (P0.05); there was no significant difference between group D and A group (P0.05); (2) the level of serum Ghrelin in group C was significantly higher than that in A group, and the difference was statistically significant (P0.05). Compared with the C group, the Ghrelin level of D group was significantly lower, and the difference was statistically significant. (3) correlation analysis serum analysis. The negative correlation between the levels and FBG, FINS, TG, CHO, LDL, HOMA-IR (R values were -0.768, -0.798, -0.64, -0.708, -0.749, etc.); (4) the expression rate of pancreatic tissue in each group was significantly higher than that in the group. Statistical significance (P0.05). Conclusion: (1) high fat diet to establish insulin resistance model, high success rate, simple process, with the formation of insulin resistance animal model, body weight, fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentration increased trend. (2) with the insulin resistance animal model The concentration of serum Ghrelin decreased, and it was negatively correlated with fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentration and insulin resistance index, and the expression of Ghrelin in the pancreas tissue decreased, suggesting that the decrease of Ghrelin secretion may be the feedback form of regulating energy balance; (3) Ghr Elin inhibits the secretion of insulin, and increases in insulin secretion when serum Ghrelin and pancreatic tissue secrete Ghrelin levels, suggesting that low Ghrelin may be an independent risk factor for insulin resistance and type 2 diabetes. (4) N-acetylcysteine significantly reduces fasting blood glucose in insulin resistance animal models, glycerol three Ester, cholesterol, low density lipoprotein, plasma insulin concentration, increase the level of serum Ghrelin, and increase the secretion of Ghrelin in the pancreatic tissue, thus inhibiting the secretion of insulin and improving insulin resistance.
【学位授予单位】：滨州医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1
【参考文献】
相关期刊论文 前4条
1 冼雄辉;张龙江;包忠宪;颜永萍;;Ghrelin对脂肪细胞糖代谢及胰岛素敏感性的影响[J];南方医科大学学报;2009年08期
2 马海港;张汝学;贾正平;;胰岛素抵抗动物模型的研究进展[J];国际内分泌代谢杂志;2008年01期
3 王冰;李宏亮;杨文英;萧建中;杜瑞琴;白秀平;潘琳;;大剂量抗氧化剂对高脂饲养大鼠胰岛β细胞分泌功能的影响及机制[J];浙江大学学报(医学版);2007年06期
4 毛微波,郭晓蕙,高妍,童玉,唐朝枢;Ghrelin促进大鼠胰岛素合成及高葡萄糖诱导的胰岛素分泌[J];基础医学与临床;2004年04期
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