消退素D1抑制肝脏p38MAPK活化改善2型糖尿病小鼠胰岛素抵抗的研究
发布时间：2018-08-19 16:41
【摘要】：目的:胰岛素抵抗是2型糖尿病的重要发病机制之一,目前认为胰岛素抵抗是一种慢性低度炎症,近期发现,ω-3多不饱和脂肪酸的衍生物—消退素是一种新型的抗炎介质,其在慢性炎症中有着“刹车信号”的作用。消退素D1(RVD1)是消退素中的重要一员,那么RVD1是否可以通过抗炎作用改善2型糖尿病小鼠的胰岛素抵抗以及其机制是什么?为了明确上述问题,我们进行了此项研究。方法:选取35只C57BL/6雄性小鼠,高脂喂养结合单次腹腔注射小剂量链脲佐菌素(Streptozotocin,STZ)建立具有胰岛素抵抗的2型糖尿病小鼠模型,随机分为空白对照组(Con组)、2型糖尿病组(T2DM组)、2型糖尿病+RVD1干预组(T2DM+RVD1组),RVD1干预21天,期间定期检测小鼠体重及血糖,实验结束后取血测甘油三酯、总胆固醇、胰岛素水平,以及计算胰岛素抵抗指数,取血后迅速解剖小鼠,留取新鲜肝脏组织用于检测TNF-α、IL-6、p38MAPK、pp38MAPK的水平。结果:1小鼠一般情况的变化Con组小鼠一直维持良好的精神状态,亮泽的毛发,灵活的活动,饮食、大便、小便无异常,未见死亡;T2DM组和T2DM+RVD1组小鼠精神状态欠佳,有多尿、多饮、多食等糖尿病的相关症状,毛发黯淡无光,行动缓慢。但与T2DM组小鼠比较,T2DM+RVD1组小鼠上述情况均有所改善。Con组小鼠体重缓慢增长;T2DM组和T2DM+RVD1组在造模前体重增加迅速,造模后体重增长相对缓慢。与Con组相比,T2DM组和T2DM+RVD1组小鼠体重明显增加,差异有统计学意义(P0.05)。与T2DM组相比,T2DM+RVD1组体重在RVD1干预1周前无明显差异,在RVD1干预2周后,T2DM+RVD1组体重有所下降,差异有统计学意义(P0.05)。2小鼠生化指标和胰岛素抵抗指标的变化2.1小鼠血糖的变化Con组小鼠血糖维持正常水平,T2DM组和T2DM+RVD1组血糖在应用高脂饲料喂养8周后出现糖调节受损,造模后血糖升高更明显。与Con组相比较,T2DM组及T2DM+RVD1组小鼠血糖明显升高,尤其是建立2型糖尿病模型后,差异有统计学意义(P0.05)。与T2DM组相比,T2DM+RVD1组血糖在RVD1干预1周之前血糖无明显变化,差异无统计学意义(P0.05)。但是在RVD1干预2周后,T2DM+RVD1组小鼠血糖较T2DM组有所降低,差异有统计学意义(P0.05)。2.2小鼠血脂的变化与Con组相比较,T2DM组及T2DM+RVD1组小鼠总胆固醇及甘油三酯升高,差异有统计学意义(P0.05)。与T2DM组相比较,T2DM+RVD1组小鼠总胆固醇及甘油三酯有所降低,差异有统计学意义(P0.05)。2.3血清胰岛素水平变化与Con组相比较,T2DM及T2DM+RVD1组小鼠胰岛素水平明显升高,差异有统计学意义(P0.05)。与T2DM组相比较,T2DM+RVD1组小鼠的胰岛素水平有所降低,差异有统计学意义(P0.05)。2.4胰岛素抵抗指数的变化与Con组相比较,T2DM及T2DM+RVD1组小鼠胰岛素抵抗指数高,差异有统计学意义(P0.05)。与T2DM组相比较,T2DM+RVD1组小鼠胰岛素抵抗指数明显降低,差异有有统计学意义(P0.05)。3小鼠肝脏炎性指标的变化3.1小鼠肝脏IL-6、TNF-α水平的变化与Con组相比较,T2DM及T2DM+RVD1组小鼠肝脏中TNF-α、IL-6升高,差异有统计学意义(P0.05)。与T2DM组相比较,T2DM+RVD1组小鼠肝脏中TNF-α、IL-6降低,差异有统计学意义(P0.05)。3.2小鼠肝脏组织中p38MAPK活化水平。与Con组相比较,T2DM及T2DM+RVD1组小鼠肝脏中pp38MAPK/p38MAPk比值升高,差异有统计学意义(P0.05)。与T2DM组相比较,T2DM+RVD1组小鼠肝脏中pp38MAPK/p38MAPK比值降低,差异有统计学意义(P0.05)。结论:1 RVD1降低2型糖尿病小鼠的体重、血糖、甘油三酯、总胆固醇、胰岛素以及胰岛素抵抗指数,改善了2型糖尿病小鼠的胰岛素抵抗。2 RVD1降低了肝脏中炎症因子TNF-α、IL-6水平,改善了肝脏的胰岛素抵抗。3 RVD1可能通过抑制了肝脏中p38MAPK炎症信号的通路,减少了肝脏炎症因子的产生,改善了肝脏的胰岛素抵抗。
[Abstract]:OBJECTIVE: Insulin resistance is one of the important pathogenesis of type 2 diabetes mellitus. Insulin resistance is currently considered to be a chronic low-grade inflammation. Recently, it has been found that_-3 polyunsaturated fatty acid derivative, receptionin, is a new anti-inflammatory mediator and plays a role of "brake signal" in chronic inflammation. To clarify these questions, we conducted this study. METHODS: Thirty-five male C57BL/6 mice were fed with high fat diet combined with a single intraperitoneal injection of low dose streptozotocin (STZ). The model of type 2 diabetes mellitus with insulin resistance was established and randomly divided into control group (Con group), type 2 diabetes mellitus group (T2DM group), type 2 diabetes mellitus + RVD1 intervention group (T2DM + RVD1 group) and RVD1 intervention group (T2DM + RVD1 group). The body weight and blood glucose of the mice were measured regularly during the intervention period of 21 days. Result: 1. The mice in the Con group had maintained good mental state, bright hair, flexible movement, diet, stool and urine without abnormalities, and no death was observed in the T2DM group and the T2DM + RVD1 group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. Compared with the control group, the weight of mice in T2DM group and T2DM+RVD1 group increased significantly (P 0.05). Compared with the T2DM group, the weight of mice in T2DM+RVD1 group had no significant difference before RVD1 intervention for one week. After RVD1 intervention for two weeks, the weight of mice in T2DM+RVD1 group decreased, and the difference was statistically significant (P 0.05). The blood glucose level of Con group and T2DM+RVD1 group was normal. The glucose regulation of T2DM group and T2DM+RVD1 group was impaired after 8 weeks feeding with high fat diet, and the blood glucose increased more significantly after modeling. Compared with Con group, the blood glucose of T2DM group and T2DM+RVD1 group increased significantly, especially after the establishment of type 2 diabetes mellitus model. Compared with T2DM group, the blood glucose of T2DM + RVD1 group had no significant change before RVD1 intervention for 1 week (P 0.05). But after RVD1 intervention for 2 weeks, the blood glucose of T2DM + RVD1 group was lower than that of T2DM group, and the difference was statistically significant (P 0.05). The total cholesterol and triglyceride levels of mice in T2DM + RVD1 group were lower than those in T2DM group (P 0.05). 2.3 Serum insulin levels in T2DM and T2DM + RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with the T2DM group, the insulin level of the T2DM + RVD1 group was lower, and the difference was statistically significant (P 0.05). The insulin resistance index of the T2DM + RVD1 group was higher than that of the Con group (P 0.05). Compared with the T2DM + RVD1 group, the insulin resistance index of the T2DM + RVD1 group was higher, and the difference was statistically significant (P 0.05). The levels of IL-6 and TNF-alpha in liver of mice in T2DM and T2DM+RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with T2DM group, the levels of TNF-alpha and IL-6 in liver of mice in T2DM+RVD1 group were significantly higher (P 0.05). Compared with the control group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM and T2DM + RVD1 groups was higher (P 0.05). Compared with the T2DM group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM + RVD1 group was lower (P Conclusion: 1 RVD1 can decrease body weight, blood glucose, triglyceride, total cholesterol, insulin and insulin resistance index in type 2 diabetic mice, and improve insulin resistance in type 2 diabetic mice. APK inflammatory signaling pathway reduces the production of liver inflammatory factors and improves insulin resistance in the liver.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1
本文编号：2192229
[Abstract]:OBJECTIVE: Insulin resistance is one of the important pathogenesis of type 2 diabetes mellitus. Insulin resistance is currently considered to be a chronic low-grade inflammation. Recently, it has been found that_-3 polyunsaturated fatty acid derivative, receptionin, is a new anti-inflammatory mediator and plays a role of "brake signal" in chronic inflammation. To clarify these questions, we conducted this study. METHODS: Thirty-five male C57BL/6 mice were fed with high fat diet combined with a single intraperitoneal injection of low dose streptozotocin (STZ). The model of type 2 diabetes mellitus with insulin resistance was established and randomly divided into control group (Con group), type 2 diabetes mellitus group (T2DM group), type 2 diabetes mellitus + RVD1 intervention group (T2DM + RVD1 group) and RVD1 intervention group (T2DM + RVD1 group). The body weight and blood glucose of the mice were measured regularly during the intervention period of 21 days. Result: 1. The mice in the Con group had maintained good mental state, bright hair, flexible movement, diet, stool and urine without abnormalities, and no death was observed in the T2DM group and the T2DM + RVD1 group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. Compared with the control group, the weight of mice in T2DM group and T2DM+RVD1 group increased significantly (P 0.05). Compared with the T2DM group, the weight of mice in T2DM+RVD1 group had no significant difference before RVD1 intervention for one week. After RVD1 intervention for two weeks, the weight of mice in T2DM+RVD1 group decreased, and the difference was statistically significant (P 0.05). The blood glucose level of Con group and T2DM+RVD1 group was normal. The glucose regulation of T2DM group and T2DM+RVD1 group was impaired after 8 weeks feeding with high fat diet, and the blood glucose increased more significantly after modeling. Compared with Con group, the blood glucose of T2DM group and T2DM+RVD1 group increased significantly, especially after the establishment of type 2 diabetes mellitus model. Compared with T2DM group, the blood glucose of T2DM + RVD1 group had no significant change before RVD1 intervention for 1 week (P 0.05). But after RVD1 intervention for 2 weeks, the blood glucose of T2DM + RVD1 group was lower than that of T2DM group, and the difference was statistically significant (P 0.05). The total cholesterol and triglyceride levels of mice in T2DM + RVD1 group were lower than those in T2DM group (P 0.05). 2.3 Serum insulin levels in T2DM and T2DM + RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with the T2DM group, the insulin level of the T2DM + RVD1 group was lower, and the difference was statistically significant (P 0.05). The insulin resistance index of the T2DM + RVD1 group was higher than that of the Con group (P 0.05). Compared with the T2DM + RVD1 group, the insulin resistance index of the T2DM + RVD1 group was higher, and the difference was statistically significant (P 0.05). The levels of IL-6 and TNF-alpha in liver of mice in T2DM and T2DM+RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with T2DM group, the levels of TNF-alpha and IL-6 in liver of mice in T2DM+RVD1 group were significantly higher (P 0.05). Compared with the control group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM and T2DM + RVD1 groups was higher (P 0.05). Compared with the T2DM group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM + RVD1 group was lower (P Conclusion: 1 RVD1 can decrease body weight, blood glucose, triglyceride, total cholesterol, insulin and insulin resistance index in type 2 diabetic mice, and improve insulin resistance in type 2 diabetic mice. APK inflammatory signaling pathway reduces the production of liver inflammatory factors and improves insulin resistance in the liver.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1
【参考文献】
相关期刊论文 前3条
1 张毅;李慧颖;董玲;高峰;;链脲佐菌素诱导模拟2型糖尿病动物模型的研究进展[J];中华糖尿病杂志;2011年05期
2 姜骊;陈辉;何勇;鱼达;;高脂饮食加低剂量链脲霉素建立小鼠2型糖尿病模型[J];中国比较医学杂志;2010年03期
3 张山佳,丁树哲;2型糖尿病发病机制研究:肿瘤坏死因子α与胰岛素抵抗的关系[J];中国临床康复;2005年07期
，本文编号：2192229
本文链接：https://www.wllwen.com/yixuelunwen/nfm/2192229.html
最近更新
教材专著
