福辛普利对胰岛素抵抗小鼠脂联素及心室重构的影响
发布时间：2018-07-28 10:59
【摘要】：目的:观察福辛普利(Fosinopril)对胰岛素抵抗(IR)小鼠脂联素(APN)、脂联素受体1(Adipo R1)、心肌细胞凋亡率及心室重构的影响。方法:随机将50只雄性C57BL/6野生型小鼠分为正常对照组、IR组、Fos7.5组、Fos15组和Fos30组,每组10只。正常对照组给予普通饲料喂养,其余四组给予高脂饲料喂养,其中Fos7.5组、Fos15组和Fos30组每日同一时间给予不同剂量福辛普利灌胃,每周称量体重,饮食量。喂养12周后测定空腹血糖及空腹胰岛素,并计算胰岛素抵抗指数(HOMA-IR);采用超声心动图检测左心室后壁厚度、室间隔厚度、LVEF和LVFS;测定全心重量、左心室重量及左心室重量指数(LVWI);HE染色观察心肌细胞形态学变化;ELISA法测定血清中TGF-β1及APN水平;TUNEL法检测心肌细胞凋亡率变化;免疫组织化学和Western blot法测定心肌组织中TGF-β1、APN和Adipo R1蛋白表达水平,PCR法测定心肌组织中APN及Adipo R1 m RNA的表达。结果:(1)与正常对照组相比,IR组小鼠空腹血糖、空腹胰岛素及HOMA-IR均明显升高,左心室后壁厚度及室间隔厚度增加,LVEF和LVFS降低,体重、全心重量及左心室重量增加,LVWI减小,心肌纤维断裂明显,排列紊乱,细胞核大小不一,心肌细胞凋亡率明显增加;血清中TGF-β1蛋白水平增高,APN蛋白水平降低;心肌组织中TGF-β1蛋白表达增高,APN及Adipo R1蛋白表达降低,APN及Adipo R1 m RNA表达均降低(P0.05);(2)与IR组相比:不同剂量福辛普利干预后空腹血糖、空腹胰岛素水平及HOMA-IR均降低,左心室后壁厚度及室间隔厚度均减小,LVEF和LVFS升高,体重、全心重量、左心室重量及LVWI均减少,心肌纤维断裂改善,排列较整齐,细胞核大小较均一,心肌细胞凋亡率明显改善;血清中TGF-β1蛋白水平降低,APN蛋白水平升高,心肌组织中TGF-β1蛋白表达降低,APN及Adipo R1蛋白表达升高,APN及Adipo R1 m RNA表达均增高。且上述观察指标随着福辛普利干预剂量的增高,效果更显著(P0.05)结论高脂饮食可以诱发胰岛素抵抗,胰岛素抵抗小鼠可出现心肌细胞凋亡增加,并存在心室重构。福辛普利可以改善胰岛素抵抗、降低心肌细胞凋亡率并预防和抑制心室重构,这种作用可能与APN及Adipo R1表达升高有关。且呈剂量依赖性。
[Abstract]:Aim: to observe the effects of fosinopril (Fosinopril) on adiponectin (APN), adiponectin receptor 1 (Adipo R1), myocardial apoptosis rate and ventricular remodeling in insulin-resistant (IR) mice. Methods: fifty male C57BL/6 wild-type mice were randomly divided into two groups: normal control group, Fos7.5 group, Fos15 group and Fos30 group, 10 mice in each group. The normal control group was fed with normal diet and the other four groups were fed with high fat diet. The Fos7.5 group Fos15 group and the Fos30 group were given different doses of fosinopril intragastrically at the same time daily. Fasting blood glucose and fasting insulin were measured and insulin resistance index (HOMA-IR) was calculated, left ventricular posterior wall thickness, ventricular septal thickness and ventricular septal thickness were measured by echocardiography, total heart weight was measured after 12 weeks of feeding. Left ventricular weight and left ventricular mass index (LVWI) HE staining were used to observe the morphological changes of cardiomyocytes. The levels of TGF- 尾 1 and APN in serum were measured by Elisa and Tunel was used to detect the apoptosis rate of cardiomyocytes. The expression level of TGF- 尾 1 APN and Adipo R1 protein in myocardial tissue was determined by immunohistochemistry and Western blot method. APN and Adipo R1 m RNA expression in myocardial tissue were detected by polymerase chain reaction (Western blot). Results: (1) compared with the control group, fasting blood glucose, fasting insulin and HOMA-IR in IR group were significantly increased, left ventricular posterior wall thickness and interventricular septal thickness increased and LVEF and LVFS decreased, body weight, whole heart weight and left ventricular weight increased and decreased. The myocardial fibers were broken, arranged disorderly, the nuclear size was different, the apoptosis rate of cardiac myocytes was increased obviously, the level of TGF- 尾 1 protein in serum was increased and the level of APN protein was decreased. The expression of TGF- 尾 1 protein in myocardial tissue increased the expression of APN and Adipo R1 protein decreased (P0.05); (2): compared with IR group, fasting blood glucose, fasting insulin level and HOMA-IR were decreased after different doses of fosinopril. The left ventricular posterior wall thickness and interventricular septal thickness decreased, the weight, total heart weight, left ventricular weight and LVWI decreased, myocardial fiber fragmentation was improved, the nuclear size was uniform, and the apoptosis rate of myocardial cells was significantly improved. The level of TGF- 尾 1 protein in serum decreased and the expression of TGF- 尾 1 protein increased, and the expression of TGF- 尾 1 protein in myocardial tissue decreased. The expression of APN- 尾 1 protein and Adipo R1 protein increased. The expression of APN and Adipo R1m RNA increased. With the increase of fosinopril intervention dose, the effect was more significant (P0.05). Conclusion High-fat diet can induce insulin resistance, insulin resistance mice may have increased cardiomyocyte apoptosis and ventricular remodeling. Fosinopril can improve insulin resistance, decrease myocardial apoptosis and prevent and inhibit ventricular remodeling, which may be related to the increased expression of APN and Adipo R1. And in a dose-dependent manner.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R54
本文编号：2149898
[Abstract]:Aim: to observe the effects of fosinopril (Fosinopril) on adiponectin (APN), adiponectin receptor 1 (Adipo R1), myocardial apoptosis rate and ventricular remodeling in insulin-resistant (IR) mice. Methods: fifty male C57BL/6 wild-type mice were randomly divided into two groups: normal control group, Fos7.5 group, Fos15 group and Fos30 group, 10 mice in each group. The normal control group was fed with normal diet and the other four groups were fed with high fat diet. The Fos7.5 group Fos15 group and the Fos30 group were given different doses of fosinopril intragastrically at the same time daily. Fasting blood glucose and fasting insulin were measured and insulin resistance index (HOMA-IR) was calculated, left ventricular posterior wall thickness, ventricular septal thickness and ventricular septal thickness were measured by echocardiography, total heart weight was measured after 12 weeks of feeding. Left ventricular weight and left ventricular mass index (LVWI) HE staining were used to observe the morphological changes of cardiomyocytes. The levels of TGF- 尾 1 and APN in serum were measured by Elisa and Tunel was used to detect the apoptosis rate of cardiomyocytes. The expression level of TGF- 尾 1 APN and Adipo R1 protein in myocardial tissue was determined by immunohistochemistry and Western blot method. APN and Adipo R1 m RNA expression in myocardial tissue were detected by polymerase chain reaction (Western blot). Results: (1) compared with the control group, fasting blood glucose, fasting insulin and HOMA-IR in IR group were significantly increased, left ventricular posterior wall thickness and interventricular septal thickness increased and LVEF and LVFS decreased, body weight, whole heart weight and left ventricular weight increased and decreased. The myocardial fibers were broken, arranged disorderly, the nuclear size was different, the apoptosis rate of cardiac myocytes was increased obviously, the level of TGF- 尾 1 protein in serum was increased and the level of APN protein was decreased. The expression of TGF- 尾 1 protein in myocardial tissue increased the expression of APN and Adipo R1 protein decreased (P0.05); (2): compared with IR group, fasting blood glucose, fasting insulin level and HOMA-IR were decreased after different doses of fosinopril. The left ventricular posterior wall thickness and interventricular septal thickness decreased, the weight, total heart weight, left ventricular weight and LVWI decreased, myocardial fiber fragmentation was improved, the nuclear size was uniform, and the apoptosis rate of myocardial cells was significantly improved. The level of TGF- 尾 1 protein in serum decreased and the expression of TGF- 尾 1 protein increased, and the expression of TGF- 尾 1 protein in myocardial tissue decreased. The expression of APN- 尾 1 protein and Adipo R1 protein increased. The expression of APN and Adipo R1m RNA increased. With the increase of fosinopril intervention dose, the effect was more significant (P0.05). Conclusion High-fat diet can induce insulin resistance, insulin resistance mice may have increased cardiomyocyte apoptosis and ventricular remodeling. Fosinopril can improve insulin resistance, decrease myocardial apoptosis and prevent and inhibit ventricular remodeling, which may be related to the increased expression of APN and Adipo R1. And in a dose-dependent manner.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R54
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