運(yùn)動(dòng)誘導(dǎo)的miR-222在糖尿病心肌中的保護(hù)作用及機(jī)制研究
發(fā)布時(shí)間：2018-11-11 21:53
【摘要】：第一章糖尿病患者心臟結(jié)構(gòu)及心功能改變情況目的探討糖尿病患者心臟結(jié)構(gòu)及心功能改變情況,以明確長期高血糖所致具體的心臟損害表現(xiàn)。方法隨機(jī)納入615例糖尿病患者,根據(jù)是否出現(xiàn)心血管并發(fā)癥分為單純糖尿病組(DM組)及出現(xiàn)心血管并發(fā)癥組(DM+CAD組),記錄患者一般臨床資料、心臟結(jié)構(gòu)和心功能情況。結(jié)果(1)DM+CAD組年齡、病程、收縮壓、空腹C肽均明顯高于DM組(P0.05),但心率、糖化血紅蛋白、空腹血糖、餐后血糖低于單純DM組(P0.05)。(2)DM+CAD組左心房內(nèi)徑、左室舒張末期內(nèi)徑、室間隔厚度、左室后壁厚度明顯高于DM組(P0.05)。(3)糖尿病患者收縮壓、體質(zhì)指數(shù)、空腹C肽與左心房內(nèi)徑、室間隔厚度、左室后壁厚度呈正相關(guān)(P0.05),而糖化血紅蛋白與左室射血分?jǐn)?shù)(left ventricular ejection fraction,LVEF)、左室短軸縮短率(left ventricular shortening fraction,LVFS)呈負(fù)相關(guān)(P＜0.05)。結(jié)論長期高糖會導(dǎo)致心腔增大,室壁增厚,加重心臟結(jié)構(gòu)重構(gòu);加強(qiáng)血糖控制、降低HbAlc是預(yù)防糖尿病并發(fā)癥的重要措施之一。第二章運(yùn)動(dòng)對糖尿病鼠的心肌保護(hù)作用與miR-222的相關(guān)機(jī)制研究目的研究運(yùn)動(dòng)在糖尿病小鼠心肌損害中的保護(hù)作用與miR-222之間的相關(guān)性及可能信號通路;探討miR-222對糖尿病小鼠心肌中第10號染色體缺失的磷酸酶及張力蛋白同源物(PTEN)、磷脂酰肌醇-3-激酶(phosphatidylinositol3kinase,PI3K)、蛋白激酶B(protein kinase B,PKB,即Akt)蛋白表達(dá)的影響。方法將C57BL/6小鼠隨機(jī)分成正常組(NC組,n=16)和DM模型組(DM組,n=20)。模型建立成功后,進(jìn)一步分成正常非運(yùn)動(dòng)組(Con-Se,n=8)、正常運(yùn)動(dòng)組(Con-Ex,n=8)、糖尿病非運(yùn)動(dòng)組(DM-Se,n=10)和糖尿病運(yùn)動(dòng)組(DM-Ex,n=10)4組。5周的游泳運(yùn)動(dòng)干預(yù)后,超聲診斷儀檢測小鼠心臟收縮功能;光鏡下觀察各組小鼠心肌病理學(xué)改變;RT-PCR法測定小鼠心肌組織miR-222、ANP及β-MHC mRNA水平;Western Blot檢測相關(guān)蛋白表達(dá)水平。結(jié)果(1)DM-Se 組小鼠 LVEF 及 LVFS 均低于 NC 組及 DM-Ex 組(P0.05);(2)NC組小鼠心肌組織未見病理改變,DM組均出現(xiàn)明顯心肌組織的病理改變,且DM-Se組病理改變更嚴(yán)重;(3)與NC組相比,DM小鼠心肌內(nèi)胚胎基因ANP及β-MHCmRNA水平明顯增加(P0.05),并且以DM-Se組增加更顯著(P0.05);(4)運(yùn)動(dòng)后小鼠心肌中miR-222表達(dá)均增加,即Con-Ex、DM-Ex組中miR-222表達(dá)較相應(yīng)無運(yùn)動(dòng)干預(yù)組表達(dá)增加(P0.05);(5)與Con-Se組相比,DM-Se、DM-Ex組小鼠心肌中PTEN蛋白表達(dá)均明顯增加,并以DM-Se組增加更為顯著(P0.05);(6)與 Con-Se 組、DM-Se 組比較,DM-Se 組 PI3K(p85)、PI3K(p110α)、p-Akt蛋白表達(dá)明顯降低(P0.05);結(jié)論運(yùn)動(dòng)可以緩解高糖狀態(tài)導(dǎo)致的小鼠心肌病理形態(tài)學(xué)改變、改善糖尿病小鼠心功能;運(yùn)動(dòng)誘導(dǎo)的miR-222可能通過負(fù)向調(diào)節(jié)PTEN蛋白表達(dá),達(dá)到間接調(diào)控PI3K/Akt信號通路而發(fā)揮心肌保護(hù)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 偽) 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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.2;R54
本文編號：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 偽) 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.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.2;R54
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1 位庚;郭勇英;賈振華;;發(fā)育成熟心臟中血管內(nèi)皮細(xì)胞和心肌細(xì)胞的關(guān)系[J];中國老年學(xué)雜志;2015年19期
2 孫莉敏,胡永善,吳毅,李益明,朱尚權(quán);運(yùn)動(dòng)對糖尿病大鼠血清瘦素水平的影響[J];中華物理醫(yī)學(xué)與康復(fù)雜志;2001年05期
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