运动诱导的miR-222在糖尿病心肌中的保护作用及机制研究
发布时间：2018-11-11 21:53
【摘要】：第一章糖尿病患者心脏结构及心功能改变情况目的探讨糖尿病患者心脏结构及心功能改变情况,以明确长期高血糖所致具体的心脏损害表现。方法随机纳入615例糖尿病患者,根据是否出现心血管并发症分为单纯糖尿病组(DM组)及出现心血管并发症组(DM+CAD组),记录患者一般临床资料、心脏结构和心功能情况。结果(1)DM+CAD组年龄、病程、收缩压、空腹C肽均明显高于DM组(P0.05),但心率、糖化血红蛋白、空腹血糖、餐后血糖低于单纯DM组(P0.05)。(2)DM+CAD组左心房内径、左室舒张末期内径、室间隔厚度、左室后壁厚度明显高于DM组(P0.05)。(3)糖尿病患者收缩压、体质指数、空腹C肽与左心房内径、室间隔厚度、左室后壁厚度呈正相关(P0.05),而糖化血红蛋白与左室射血分数(left ventricular ejection fraction,LVEF)、左室短轴缩短率(left ventricular shortening fraction,LVFS)呈负相关(P＜0.05)。结论长期高糖会导致心腔增大,室壁增厚,加重心脏结构重构;加强血糖控制、降低HbAlc是预防糖尿病并发症的重要措施之一。第二章运动对糖尿病鼠的心肌保护作用与miR-222的相关机制研究目的研究运动在糖尿病小鼠心肌损害中的保护作用与miR-222之间的相关性及可能信号通路;探讨miR-222对糖尿病小鼠心肌中第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN)、磷脂酰肌醇-3-激酶(phosphatidylinositol3kinase,PI3K)、蛋白激酶B(protein kinase B,PKB,即Akt)蛋白表达的影响。方法将C57BL/6小鼠随机分成正常组(NC组,n=16)和DM模型组(DM组,n=20)。模型建立成功后,进一步分成正常非运动组(Con-Se,n=8)、正常运动组(Con-Ex,n=8)、糖尿病非运动组(DM-Se,n=10)和糖尿病运动组(DM-Ex,n=10)4组。5周的游泳运动干预后,超声诊断仪检测小鼠心脏收缩功能;光镜下观察各组小鼠心肌病理学改变;RT-PCR法测定小鼠心肌组织miR-222、ANP及β-MHC mRNA水平;Western Blot检测相关蛋白表达水平。结果(1)DM-Se 组小鼠 LVEF 及 LVFS 均低于 NC 组及 DM-Ex 组(P0.05);(2)NC组小鼠心肌组织未见病理改变,DM组均出现明显心肌组织的病理改变,且DM-Se组病理改变更严重;(3)与NC组相比,DM小鼠心肌内胚胎基因ANP及β-MHCmRNA水平明显增加(P0.05),并且以DM-Se组增加更显著(P0.05);(4)运动后小鼠心肌中miR-222表达均增加,即Con-Ex、DM-Ex组中miR-222表达较相应无运动干预组表达增加(P0.05);(5)与Con-Se组相比,DM-Se、DM-Ex组小鼠心肌中PTEN蛋白表达均明显增加,并以DM-Se组增加更为显著(P0.05);(6)与 Con-Se 组、DM-Se 组比较,DM-Se 组 PI3K(p85)、PI3K(p110α)、p-Akt蛋白表达明显降低(P0.05);结论运动可以缓解高糖状态导致的小鼠心肌病理形态学改变、改善糖尿病小鼠心功能;运动诱导的miR-222可能通过负向调节PTEN蛋白表达,达到间接调控PI3K/Akt信号通路而发挥心肌保护作用。
[Abstract]:Chapter 1 changes of cardiac structure and cardiac function in diabetic patients objective to investigate the changes of cardiac structure and cardiac function in diabetic patients in order to determine the specific cardiac damage caused by long-term hyperglycemia. Methods 615 patients with diabetes were randomly divided into simple diabetes group (DM group) and cardiovascular complication group (DM CAD group) according to whether there were cardiovascular complications. The general clinical data, cardiac structure and cardiac function were recorded. Results (1) Age, course of disease, systolic blood pressure, fasting C-peptide in) DM CAD group were significantly higher than those in DM group (P0.05), but heart rate, glycosylated hemoglobin, fasting blood glucose were significantly higher than those in DM group. Postprandial blood glucose levels in DM group were significantly lower than those in DM group (P0.05). (2) DM CAD group, P 0.05). (2) DM CAD group, left ventricular end-diastolic diameter, left ventricular septal thickness, left ventricular posterior wall thickness significantly higher than that in DM group (P0.05). (3). Body mass index, fasting C-peptide and left atrial diameter, interventricular septal thickness, left ventricular posterior wall thickness were positively correlated (P0.05), while glycosylated hemoglobin was correlated with left ventricular ejection fraction (left ventricular ejection fraction,LVEF), left ventricular short axis shortening rate (left ventricular shortening fraction,). LVFS was negatively correlated (P < 0. 05). Conclusion Long-term hyperglycemia will lead to cardiac cavity enlargement, ventricular wall thickening and cardiac structural remodeling, and strengthening blood glucose control and reducing HbAlc is one of the important measures to prevent diabetic complications. Chapter 2 study on the relationship between myocardial protective effect of exercise and miR-222 in diabetic mice objective to study the relationship between the protective effect of exercise and miR-222 and the possible signal pathway in diabetic mice. To investigate the effect of miR-222 on the expression of phosphatase and (PTEN), phosphatidylinositol 3-kinase (phosphatidylinositol3kinase,PI3K) and protein kinase (B (protein kinase) PKB (Akt) in the myocardium of diabetic mice. Methods C57BL/6 mice were randomly divided into normal group (NC group, nong16) and DM model group (DM group, nong20). After the model was established successfully, it was further divided into normal non-exercise group (Con-Se,n=8), normal exercise group (Con-Ex,n=8), diabetic non-exercise group (DM-Se,n=10) and diabetic exercise group (DM-Ex,). After 5 weeks of swimming intervention, the cardiac contractile function of mice was measured by ultrasonic diagnostic instrument. The pathological changes of myocardium in each group were observed under light microscope, and the expression levels of miR-222,ANP and 尾-MHC mRNA in myocardium were detected by RT-PCR method, and the expression of related proteins was detected by; Western Blot. Results (1) LVEF and LVFS in DM-Se group were lower than those in NC group and DM-Ex group (P0.05). (2) there were no pathological changes in myocardial tissue in NC group, but there were obvious pathological changes in myocardial tissue in DM group, and the pathological changes in DM-Se group were more serious. (3) compared with NC group, the levels of ANP and 尾-MHCmRNA in myocardium of DM mice were significantly increased (P0.05), especially in DM-Se group (P0.05). (4) the expression of miR-222 in myocardium increased after exercise, that is, the expression of miR-222 in Con-Ex,DM-Ex group was higher than that in control group (P0.05). (5) compared with Con-Se group, the expression of PTEN protein in DM-Se,DM-Ex group was significantly increased, especially in DM-Se group (P0.05). (6) compared with Con-Se group and DM-Se group, the expression of PI3K (p85), PI3K (p110 伪) and p-Akt protein in DM-Se group were significantly decreased (P0.05). Conclusion exercise can alleviate the pathomorphological changes of cardiomyopathy induced by high glucose state in mice and improve the cardiac function of diabetic mice. Exercise induced miR-222 may play a role in myocardial protection by negatively regulating the expression of PTEN protein and indirectly regulating the PI3K/Akt signaling pathway.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R54
本文编号：2326242
[Abstract]:Chapter 1 changes of cardiac structure and cardiac function in diabetic patients objective to investigate the changes of cardiac structure and cardiac function in diabetic patients in order to determine the specific cardiac damage caused by long-term hyperglycemia. Methods 615 patients with diabetes were randomly divided into simple diabetes group (DM group) and cardiovascular complication group (DM CAD group) according to whether there were cardiovascular complications. The general clinical data, cardiac structure and cardiac function were recorded. Results (1) Age, course of disease, systolic blood pressure, fasting C-peptide in) DM CAD group were significantly higher than those in DM group (P0.05), but heart rate, glycosylated hemoglobin, fasting blood glucose were significantly higher than those in DM group. Postprandial blood glucose levels in DM group were significantly lower than those in DM group (P0.05). (2) DM CAD group, P 0.05). (2) DM CAD group, left ventricular end-diastolic diameter, left ventricular septal thickness, left ventricular posterior wall thickness significantly higher than that in DM group (P0.05). (3). Body mass index, fasting C-peptide and left atrial diameter, interventricular septal thickness, left ventricular posterior wall thickness were positively correlated (P0.05), while glycosylated hemoglobin was correlated with left ventricular ejection fraction (left ventricular ejection fraction,LVEF), left ventricular short axis shortening rate (left ventricular shortening fraction,). LVFS was negatively correlated (P < 0. 05). Conclusion Long-term hyperglycemia will lead to cardiac cavity enlargement, ventricular wall thickening and cardiac structural remodeling, and strengthening blood glucose control and reducing HbAlc is one of the important measures to prevent diabetic complications. Chapter 2 study on the relationship between myocardial protective effect of exercise and miR-222 in diabetic mice objective to study the relationship between the protective effect of exercise and miR-222 and the possible signal pathway in diabetic mice. To investigate the effect of miR-222 on the expression of phosphatase and (PTEN), phosphatidylinositol 3-kinase (phosphatidylinositol3kinase,PI3K) and protein kinase (B (protein kinase) PKB (Akt) in the myocardium of diabetic mice. Methods C57BL/6 mice were randomly divided into normal group (NC group, nong16) and DM model group (DM group, nong20). After the model was established successfully, it was further divided into normal non-exercise group (Con-Se,n=8), normal exercise group (Con-Ex,n=8), diabetic non-exercise group (DM-Se,n=10) and diabetic exercise group (DM-Ex,). After 5 weeks of swimming intervention, the cardiac contractile function of mice was measured by ultrasonic diagnostic instrument. The pathological changes of myocardium in each group were observed under light microscope, and the expression levels of miR-222,ANP and 尾-MHC mRNA in myocardium were detected by RT-PCR method, and the expression of related proteins was detected by; Western Blot. Results (1) LVEF and LVFS in DM-Se group were lower than those in NC group and DM-Ex group (P0.05). (2) there were no pathological changes in myocardial tissue in NC group, but there were obvious pathological changes in myocardial tissue in DM group, and the pathological changes in DM-Se group were more serious. (3) compared with NC group, the levels of ANP and 尾-MHCmRNA in myocardium of DM mice were significantly increased (P0.05), especially in DM-Se group (P0.05). (4) the expression of miR-222 in myocardium increased after exercise, that is, the expression of miR-222 in Con-Ex,DM-Ex group was higher than that in control group (P0.05). (5) compared with Con-Se group, the expression of PTEN protein in DM-Se,DM-Ex group was significantly increased, especially in DM-Se group (P0.05). (6) compared with Con-Se group and DM-Se group, the expression of PI3K (p85), PI3K (p110 伪) and p-Akt protein in DM-Se group were significantly decreased (P0.05). Conclusion exercise can alleviate the pathomorphological changes of cardiomyopathy induced by high glucose state in mice and improve the cardiac function of diabetic mice. Exercise induced miR-222 may play a role in myocardial protection by negatively regulating the expression of PTEN protein and indirectly regulating the PI3K/Akt signaling pathway.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R54
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中国期刊全文数据库 前2条
1 位庚;郭勇英;贾振华;;发育成熟心脏中血管内皮细胞和心肌细胞的关系[J];中国老年学杂志;2015年19期
2 孙莉敏,胡永善,吴毅,李益明,朱尚权;运动对糖尿病大鼠血清瘦素水平的影响[J];中华物理医学与康复杂志;2001年05期
，本文编号：2326242
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