Ghrelin與胰島素抵抗關系的研究及氮乙酰半胱氨酸干預作用的觀察
發(fā)布時間：2018-08-05 13:51
【摘要】：目的：隨著中國社會不斷進步、經濟日益發(fā)展,人民生活的水平得以提高,衣食住行各個方面得到了前所未有的改善,從而被查出患有2型糖尿病的人民群眾愈來愈多,IDF預計到2025年全球2型糖尿病患者就達到3.88億,近幾年有關2型糖尿病的預防和治療的研究也越來越多,尤其是某些胃腸肽類激素(如胰泌素、生長抑素、瘦素等)的研究越來越受到重視,其中由胰島a、β、ε細胞及胃粘膜細胞等分泌的Ghrelin除具有增加食欲、促進攝食、增加胃酸分泌、促進胃腸動力等作用,另外在調節(jié)能量平衡、增加脂肪堆積也有一定作用,同時還可影響胰島β細胞分泌胰島素,與胰島素抵抗有一定的相關性,而2型糖尿病的發(fā)病基礎既是胰島素抵抗的產生,因此Ghrelin與肥胖、胰島素抵抗及2型糖尿病的發(fā)生有一定的相關性。另外,氧化應激對胰島β細胞的損傷是產生胰島素抵抗關鍵因素之一,應用抗氧化劑來減輕胰島素抵抗、改善胰島功能對2型糖尿病的治療意義重大。本文通過大鼠高脂飲食誘導胰島素抵抗動物模型,研究Ghrelin與胰島素抵抗的關系,并觀察氮乙酰半胱氨酸對Ghrelin及胰島素抵抗的影響。方法：40只雄性SD大鼠適應性喂養(yǎng)1周,計算機隨機分成2組：對照組A組(n=10)給予正常飲水和普通飼料(碳水化合物70%,脂肪10%,蛋白質20%)；高脂組B組(n=30)給予正常飲水和高脂飼料(碳水化合物50%,脂肪30%,蛋白質20%),共飼養(yǎng)12周。12周后,對B組采用內眥取血的方法進行采血測定空腹血糖和空腹胰島素,通過對胰島抵抗指數(shù)(HOMA-IR)進行計算,決定選用30只大鼠建立胰島素抵抗模型。胰島素抵抗動物模型建立成功后,將B組隨機分為高脂對照組(C組,n=15)和高脂干預組(D組,n=15),繼續(xù)給予A組普通飼料喂養(yǎng),C組和D組高脂飼料喂養(yǎng)；同時給予D組氮乙酰半胱氨酸200mg/(kg·d)灌胃,給予A組和C組生理鹽水灌胃,灌胃4周后采血處死大鼠,空腹血糖應用強生穩(wěn)豪血糖儀測定,甘油三酯、總膽固醇、低密度脂蛋白應用全自動生化分析儀檢測,空腹胰島素和Ghrelin采用酶聯(lián)免疫吸附試驗(ELISA)測定。SABC免疫組織化學檢測胰腺組織Ghrelin的表達。應用SPSS 13.0軟件包統(tǒng)計分析。各參數(shù)以x±s表示,組間數(shù)據(jù)采用t檢驗分析,Ghrelin與糖尿病相關指標采用Pearson相關分析。P0.05認為差異有統(tǒng)計學意義。結果：(1)各組各項指標的變化與A組比較,C組的,FBG、FINS、TG、CHO、LDL、HOMA-IR明顯升高,差異有統(tǒng)計學意義(P0.05);與C組比較,D組的FBG、FINS、TG、CHO、HOMA-IR明顯降低,差異有統(tǒng)計學意義(P0.05)；D組與A組相比較無統(tǒng)計學意義(P0.05)；(2)各組血清Ghrelin水平的變化與A組相比,C組的Ghrelin水平明顯升高,差異有統(tǒng)計學意義(P0.05)；與C組比較,D組的Ghrelin水平明顯降低,差異有統(tǒng)計學意義(P0.05)；(3)相關性分析血清ghrelin水平與FBG、FINS、TG、CHO、LDL、HOMA-IR負相關(r值分別為-0.768、-0.798、-0.64、-0.708、-0.749、-0.721,P0.05)；(4)各組胰腺組織中Ghrelin的表達：與A組相比,C組的Ghrelin的表達率明顯升高,差異有統(tǒng)計學意義(P0.05)；與C組比較,D組的Ghrelin的表達率明顯降低,差異有統(tǒng)計學意義(P0.05)。結論：(1)高脂飼料建立胰島素抵抗模型,造模成功率高,過程簡單易行,隨著胰島素抵抗動物模型的形成,體重、空腹血糖、甘油三酯、膽固醇、低密度脂蛋白、血漿胰島素濃度均呈遞增趨勢。(2)隨著胰島素抵抗動物模型的形成,血清Ghrelin的濃度呈遞減趨勢,且與空腹血糖、甘油三酯、膽固醇、低密度脂蛋白、血漿胰島素濃度及胰島素抵抗指數(shù)呈負相關,且胰腺組織中Ghrelin表達呈遞減趨勢,提示Ghrelin分泌的減少可能是機體調節(jié)能量平衡的反饋形式；(3)Ghrelin能夠抑制胰島素的分泌,而當血清Ghrelin及胰腺組織分泌Ghrelin的水平降低時,胰島素分泌增加,提示低Ghrelin血癥可能是發(fā)生胰島素抵抗、2型糖尿病的獨立危險因素。(4)氮乙酰半胱氨酸顯著降低胰島素抵抗動物模型的空腹血糖、甘油三酯、膽固醇、低密度脂蛋白、血漿胰島素濃度,升高血清Ghrelin的水平,并使胰腺組織分泌Ghrelin增加,從而抑制胰島素的分泌,改善胰島素抵抗。
[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.
【學位授予單位】：濱州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R587.1
本文編號：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.
【學位授予單位】：濱州醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R587.1
【參考文獻】
相關期刊論文 前4條
1 冼雄輝;張龍江;包忠憲;顏永萍;;Ghrelin對脂肪細胞糖代謝及胰島素敏感性的影響[J];南方醫(yī)科大學學報;2009年08期
2 馬海港;張汝學;賈正平;;胰島素抵抗動物模型的研究進展[J];國際內分泌代謝雜志;2008年01期
3 王冰;李宏亮;楊文英;蕭建中;杜瑞琴;白秀平;潘琳;;大劑量抗氧化劑對高脂飼養(yǎng)大鼠胰島β細胞分泌功能的影響及機制[J];浙江大學學報(醫(yī)學版);2007年06期
4 毛微波,郭曉蕙,高妍,童玉,唐朝樞;Ghrelin促進大鼠胰島素合成及高葡萄糖誘導的胰島素分泌[J];基礎醫(yī)學與臨床;2004年04期
，本文編號：2165988
本文鏈接：http://sikaile.net/yixuelunwen/nfm/2165988.html
最近更新
教材專著
