福辛普利對胰島素抵抗小鼠脂聯(lián)素及心室重構(gòu)的影響
發(fā)布時間：2018-07-28 10:59
【摘要】：目的:觀察福辛普利(Fosinopril)對胰島素抵抗(IR)小鼠脂聯(lián)素(APN)、脂聯(lián)素受體1(Adipo R1)、心肌細(xì)胞凋亡率及心室重構(gòu)的影響。方法:隨機(jī)將50只雄性C57BL/6野生型小鼠分為正常對照組、IR組、Fos7.5組、Fos15組和Fos30組,每組10只。正常對照組給予普通飼料喂養(yǎng),其余四組給予高脂飼料喂養(yǎng),其中Fos7.5組、Fos15組和Fos30組每日同一時間給予不同劑量福辛普利灌胃,每周稱量體重,飲食量。喂養(yǎng)12周后測定空腹血糖及空腹胰島素,并計算胰島素抵抗指數(shù)(HOMA-IR);采用超聲心動圖檢測左心室后壁厚度、室間隔厚度、LVEF和LVFS;測定全心重量、左心室重量及左心室重量指數(shù)(LVWI);HE染色觀察心肌細(xì)胞形態(tài)學(xué)變化;ELISA法測定血清中TGF-β1及APN水平;TUNEL法檢測心肌細(xì)胞凋亡率變化;免疫組織化學(xué)和Western blot法測定心肌組織中TGF-β1、APN和Adipo R1蛋白表達(dá)水平,PCR法測定心肌組織中APN及Adipo R1 m RNA的表達(dá)。結(jié)果:(1)與正常對照組相比,IR組小鼠空腹血糖、空腹胰島素及HOMA-IR均明顯升高,左心室后壁厚度及室間隔厚度增加,LVEF和LVFS降低,體重、全心重量及左心室重量增加,LVWI減小,心肌纖維斷裂明顯,排列紊亂,細(xì)胞核大小不一,心肌細(xì)胞凋亡率明顯增加;血清中TGF-β1蛋白水平增高,APN蛋白水平降低;心肌組織中TGF-β1蛋白表達(dá)增高,APN及Adipo R1蛋白表達(dá)降低,APN及Adipo R1 m RNA表達(dá)均降低(P0.05);(2)與IR組相比:不同劑量福辛普利干預(yù)后空腹血糖、空腹胰島素水平及HOMA-IR均降低,左心室后壁厚度及室間隔厚度均減小,LVEF和LVFS升高,體重、全心重量、左心室重量及LVWI均減少,心肌纖維斷裂改善,排列較整齊,細(xì)胞核大小較均一,心肌細(xì)胞凋亡率明顯改善;血清中TGF-β1蛋白水平降低,APN蛋白水平升高,心肌組織中TGF-β1蛋白表達(dá)降低,APN及Adipo R1蛋白表達(dá)升高,APN及Adipo R1 m RNA表達(dá)均增高。且上述觀察指標(biāo)隨著福辛普利干預(yù)劑量的增高,效果更顯著(P0.05)結(jié)論高脂飲食可以誘發(fā)胰島素抵抗,胰島素抵抗小鼠可出現(xiàn)心肌細(xì)胞凋亡增加,并存在心室重構(gòu)。福辛普利可以改善胰島素抵抗、降低心肌細(xì)胞凋亡率并預(yù)防和抑制心室重構(gòu),這種作用可能與APN及Adipo R1表達(dá)升高有關(guān)。且呈劑量依賴性。
[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.
【學(xué)位授予單位】：寧夏醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R54
本文編號：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.
【學(xué)位授予單位】：寧夏醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R54
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