目的探讨载脂蛋白A-Ⅰ模拟肽(L-4F)对肥胖大鼠心功能的影响及可能机制。方法 50只SD大鼠中,随机选择10只喂食普通饲料为对照组,另40只喂食高脂饲料8周后,肥胖模型造模成功率75%,将肥胖模型成功大鼠30只再随机分为肥胖组、诱导剂组[血红...目的探讨载脂蛋白A-Ⅰ模拟肽(L-4F)对肥胖大鼠心功能的影响及可能机制。方法 50只SD大鼠中,随机选择10只喂食普通饲料为对照组,另40只喂食高脂饲料8周后,肥胖模型造模成功率75%,将肥胖模型成功大鼠30只再随机分为肥胖组、诱导剂组[血红素氧合酶1(HO-1)诱导剂L-4F]和抑制剂组(HO-1抑制剂SnMP),每组10只,各组每天腹腔注射相应药物,持续8周。心脏超声和血流动力学检测后,自腹主动脉取血,ELISA检测各项指标。苏木精-伊红染色观察心肌组织病理变化;分别用RT-PCR和Western blot测心肌组织HO-1、脂联素基因和蛋白表达。结果与对照组比较,肥胖组和抑制剂组干预8周体质量较基线体质量增加显著升高(P<0.01),血糖、胰岛素、TNF-α、白细胞介素6和丙二醛水平明显升高(P<0.05,P<0.01),胆红素、超氧化物歧化酶[(3.26±0.51)μg/L和(5.90±0.49)μg/L vs (8.66±0.70)μg/L,P<0.05,P<0.01]和脂联素水平明显降低[(4.16±0.75)μg/L和(4.62±0.52)μg/L vs (6.72±1.09)μg/L,P<0.05],诱导剂组上述指标无明显变化(P>0.05);肥胖组和抑制剂组左心室舒张末期内径、左心室收缩末期内径显著增大(P<0.01),左心室短轴缩短率和LVEF及左心室最大压力最大变化速率显著降低(P<0.05,P<0.01),肥胖组左心室收缩压和左心室舒张末压明显升高(P<0.01),而诱导剂组上述指标则无明显变化(P>0.05)。肥胖组和抑制剂组心肌组织HO-1和脂联素mRNA和蛋白表达较对照组明显减低(P<0.05,P<0.01);诱导剂组HO-1和脂联素蛋白表达显著高于肥胖组和抑制剂组(P<0.01);而抑制剂组与肥胖组HO-1和脂联素蛋白表达无显著差异(P>0.05)。苏木精-伊红染色显示,肥胖组心肌细胞肥大、充血,心肌细胞间有较明显的纤维条索形成,慢性炎性反应明显,抑制剂组心肌组织也有较明显的充血、心肌细胞肥大,纤维条索形成,但是较肥胖组减轻;诱导剂组与对照组相似。结论 L-4F上调肥胖大鼠HO-1与脂联素轴,降低肥胖大鼠体质量,减轻胰岛素抵抗和炎性反应,改善氧化应激状态,抑制心肌重构,改善肥胖大鼠的心功能。展开更多
目的探讨钴原卟啉上调血红素氧合酶1(HO-1)对代谢综合征(MS)大鼠心功能的影响及相关机制。方法选择7周龄雄性高血压大鼠52只,分为对照组、MS组、MS+钴原卟啉组(钴原卟啉组)和MS+钴原卟啉+锡中卟啉组(锡中卟啉组),每组13只。采用Langendo...目的探讨钴原卟啉上调血红素氧合酶1(HO-1)对代谢综合征(MS)大鼠心功能的影响及相关机制。方法选择7周龄雄性高血压大鼠52只,分为对照组、MS组、MS+钴原卟啉组(钴原卟啉组)和MS+钴原卟啉+锡中卟啉组(锡中卟啉组),每组13只。采用Langendorff装置测量各组大鼠心脏功能和冠状动脉阻力,染色切片观察心脏横截面积和心肌纤维化程度,免疫印迹法测定心肌组织中HO-1、HO-2、环氧化酶2,氮氧化物酶2、蛋白激酶(Akt)、腺苷酸活化蛋白激酶(AMPK)、磷酸化AMPK、磷酸化Akt、脂联素、内皮型一氧化氮合酶(eNOS)、磷酸化eNOS和诱导型一氧化氮合酶(iNOS),液体闪烁计数器测量心肌超氧化物和TC水平,ELISA血浆脂联素和炎性因子水平。结果与对照组比较,MS组冠状动脉阻力明显增高(26.70±0.90 vs 19.30±0.40,P<0.05)。与MS组比较,钴原卟啉组上调HO-1后不仅改善了心功能指标,脂联素、磷酸化AMPK/AMPK、磷酸化eNOS/eNOS明显增高,iNOS明显降低(P<0.05)。结论上调HO-1可通过抑制氧化应激反应、炎性反应,提高脂联素水平,改善MS大鼠心功能。展开更多
目的探讨载脂蛋白A-Ⅰ模拟肽左旋-氨基酸(L-4F)对肥胖合并心肌梗死大鼠心功能的影响及其可能机制。方法选择7周龄雄性SD大鼠60只,对照组12只大鼠给予普通饲料喂养,其余48只大鼠给予高脂饲料喂养8周,随机分为肥胖组,心肌梗死组,L-4F组,...目的探讨载脂蛋白A-Ⅰ模拟肽左旋-氨基酸(L-4F)对肥胖合并心肌梗死大鼠心功能的影响及其可能机制。方法选择7周龄雄性SD大鼠60只,对照组12只大鼠给予普通饲料喂养,其余48只大鼠给予高脂饲料喂养8周,随机分为肥胖组,心肌梗死组,L-4F组,血红素氧化酶1(HO-1)抑制剂(SnMP)组,每组12只,后3组大鼠给予结扎冠状动脉左前降支,建立肥胖合并心肌梗死大鼠模型。干预8周后行超声心动图、血流动力学检查,包括左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、LVEF、左心室短轴缩短率(LVFS)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP),计算左心室压力最大上升及下降速率(±dp/dt_(max)),组织标本采用苏木精-伊红染色和Masson染色,ELISA检测血清脂联素,实时荧光定量PCR和Western blot检测相关基因表达,包括内质网应激蛋白(Chop)、葡萄糖调节蛋白78(GRP78)及磷酸化类蛋白激酶内质网激酶(PERK)蛋白。结果与对照组比较,肥胖组LVESD、LVEDD、LVSP、LVEDP、Chop及磷酸化PERK明显升高,LVEF、LVFS、-dp/dt_(max)、HO-1、脂联素水平明显降低;与心肌梗死组比较,L-4F组LVESD、LVEDD、LVSP、LVEDP、Chop、GRP78及磷酸化PERK明显降低,LVEF、LVFS、±dp/dt_(max)、HO-1、脂联素明显升高(P<0.05,P<0.01);与L-4F组比较,SnMP组LVESD、LVEDD、LVSP、LVEDP明显升高,Chop、GRP78及磷酸化PERK明显升高[1.14±0.15 vs 0.80±0.09,P<0.05;5.04±0.33 vs 2.96±0.22,P<0.05;16.79±0.89 vs 5.18±0.73,P<0.01],LVEF、LVFS、±dp/dt_(max)、HO-1、脂联素水平明显降低(P<0.05,P<0.01)。结论L-4F通过激活肥胖合并心肌梗死大鼠HO-1-脂联素轴,抑制内质网应激,降低心肌细胞毒性,抑制心脏重构,改善大鼠心功能。展开更多
This study was aimed to investigate the effect of stress induced by high-intensity exercises on the cardiovascular system. In the epidemiological investigation, 200 subjects（test group） engaged in special high-inten...This study was aimed to investigate the effect of stress induced by high-intensity exercises on the cardiovascular system. In the epidemiological investigation, 200 subjects（test group） engaged in special high-intensity exercises, and 97 who lived and worked in the same environment and conditions as those in the test group, but did not participate in the exercises served as controls. In the second part of the study, 50 mice were randomly divided into control group, exhaustive swimming group, white noise group, exhaustive swimming plus white noise group, and pioglitazone intervention group. The results showed that the plasma concentrations of the myocardial injury markers heart fatty acid-binding protein（H-FABP）, C-reactive protein（CRP）, β-endorphin（β-EP） and levels of psychological stress were significantly increased in test group as compared with control group; special high-intensity exercises resulted in a significant elevation of the incidence of cardiac arrhythmias. Animal experiments showed that the plasma levels of corticosterone（CORT） and troponin I（Tn I） were raised while the level of SOD was reduced in exhaustive swimming group, white noise group, and exhaustive swimming plus white noise group. The expression levels of PPARγ m RNA and protein were decreased in myocardial tissues in these groups as well. HE staining showed no remarkable change in myocardial tissues in all the groups. Treatment with pioglitazone significantly decreased the plasma levels of Tn I and CORT, while increased the level of SOD and the expression levels of PPARγ m RNA and protein. It was concluded that the high-intensity exercises may induce a heavy physical and psychological stress and predispose the subjects to accumulated fatigue and sleep deprivation; high-intensity exercises also increases the incidence of arrhythmias and myocardial injury. PPARγ may be involved in the physical and psychological changes induced by high-intensity exercises.展开更多
文摘目的探讨载脂蛋白A-Ⅰ模拟肽(L-4F)对肥胖大鼠心功能的影响及可能机制。方法 50只SD大鼠中,随机选择10只喂食普通饲料为对照组,另40只喂食高脂饲料8周后,肥胖模型造模成功率75%,将肥胖模型成功大鼠30只再随机分为肥胖组、诱导剂组[血红素氧合酶1(HO-1)诱导剂L-4F]和抑制剂组(HO-1抑制剂SnMP),每组10只,各组每天腹腔注射相应药物,持续8周。心脏超声和血流动力学检测后,自腹主动脉取血,ELISA检测各项指标。苏木精-伊红染色观察心肌组织病理变化;分别用RT-PCR和Western blot测心肌组织HO-1、脂联素基因和蛋白表达。结果与对照组比较,肥胖组和抑制剂组干预8周体质量较基线体质量增加显著升高(P<0.01),血糖、胰岛素、TNF-α、白细胞介素6和丙二醛水平明显升高(P<0.05,P<0.01),胆红素、超氧化物歧化酶[(3.26±0.51)μg/L和(5.90±0.49)μg/L vs (8.66±0.70)μg/L,P<0.05,P<0.01]和脂联素水平明显降低[(4.16±0.75)μg/L和(4.62±0.52)μg/L vs (6.72±1.09)μg/L,P<0.05],诱导剂组上述指标无明显变化(P>0.05);肥胖组和抑制剂组左心室舒张末期内径、左心室收缩末期内径显著增大(P<0.01),左心室短轴缩短率和LVEF及左心室最大压力最大变化速率显著降低(P<0.05,P<0.01),肥胖组左心室收缩压和左心室舒张末压明显升高(P<0.01),而诱导剂组上述指标则无明显变化(P>0.05)。肥胖组和抑制剂组心肌组织HO-1和脂联素mRNA和蛋白表达较对照组明显减低(P<0.05,P<0.01);诱导剂组HO-1和脂联素蛋白表达显著高于肥胖组和抑制剂组(P<0.01);而抑制剂组与肥胖组HO-1和脂联素蛋白表达无显著差异(P>0.05)。苏木精-伊红染色显示,肥胖组心肌细胞肥大、充血,心肌细胞间有较明显的纤维条索形成,慢性炎性反应明显,抑制剂组心肌组织也有较明显的充血、心肌细胞肥大,纤维条索形成,但是较肥胖组减轻;诱导剂组与对照组相似。结论 L-4F上调肥胖大鼠HO-1与脂联素轴,降低肥胖大鼠体质量,减轻胰岛素抵抗和炎性反应,改善氧化应激状态,抑制心肌重构,改善肥胖大鼠的心功能。
文摘目的探讨钴原卟啉上调血红素氧合酶1(HO-1)对代谢综合征(MS)大鼠心功能的影响及相关机制。方法选择7周龄雄性高血压大鼠52只,分为对照组、MS组、MS+钴原卟啉组(钴原卟啉组)和MS+钴原卟啉+锡中卟啉组(锡中卟啉组),每组13只。采用Langendorff装置测量各组大鼠心脏功能和冠状动脉阻力,染色切片观察心脏横截面积和心肌纤维化程度,免疫印迹法测定心肌组织中HO-1、HO-2、环氧化酶2,氮氧化物酶2、蛋白激酶(Akt)、腺苷酸活化蛋白激酶(AMPK)、磷酸化AMPK、磷酸化Akt、脂联素、内皮型一氧化氮合酶(eNOS)、磷酸化eNOS和诱导型一氧化氮合酶(iNOS),液体闪烁计数器测量心肌超氧化物和TC水平,ELISA血浆脂联素和炎性因子水平。结果与对照组比较,MS组冠状动脉阻力明显增高(26.70±0.90 vs 19.30±0.40,P<0.05)。与MS组比较,钴原卟啉组上调HO-1后不仅改善了心功能指标,脂联素、磷酸化AMPK/AMPK、磷酸化eNOS/eNOS明显增高,iNOS明显降低(P<0.05)。结论上调HO-1可通过抑制氧化应激反应、炎性反应,提高脂联素水平,改善MS大鼠心功能。
文摘目的探讨载脂蛋白A-Ⅰ模拟肽左旋-氨基酸(L-4F)对肥胖合并心肌梗死大鼠心功能的影响及其可能机制。方法选择7周龄雄性SD大鼠60只,对照组12只大鼠给予普通饲料喂养,其余48只大鼠给予高脂饲料喂养8周,随机分为肥胖组,心肌梗死组,L-4F组,血红素氧化酶1(HO-1)抑制剂(SnMP)组,每组12只,后3组大鼠给予结扎冠状动脉左前降支,建立肥胖合并心肌梗死大鼠模型。干预8周后行超声心动图、血流动力学检查,包括左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、LVEF、左心室短轴缩短率(LVFS)、左心室收缩压(LVSP)、左心室舒张末压(LVEDP),计算左心室压力最大上升及下降速率(±dp/dt_(max)),组织标本采用苏木精-伊红染色和Masson染色,ELISA检测血清脂联素,实时荧光定量PCR和Western blot检测相关基因表达,包括内质网应激蛋白(Chop)、葡萄糖调节蛋白78(GRP78)及磷酸化类蛋白激酶内质网激酶(PERK)蛋白。结果与对照组比较,肥胖组LVESD、LVEDD、LVSP、LVEDP、Chop及磷酸化PERK明显升高,LVEF、LVFS、-dp/dt_(max)、HO-1、脂联素水平明显降低;与心肌梗死组比较,L-4F组LVESD、LVEDD、LVSP、LVEDP、Chop、GRP78及磷酸化PERK明显降低,LVEF、LVFS、±dp/dt_(max)、HO-1、脂联素明显升高(P<0.05,P<0.01);与L-4F组比较,SnMP组LVESD、LVEDD、LVSP、LVEDP明显升高,Chop、GRP78及磷酸化PERK明显升高[1.14±0.15 vs 0.80±0.09,P<0.05;5.04±0.33 vs 2.96±0.22,P<0.05;16.79±0.89 vs 5.18±0.73,P<0.01],LVEF、LVFS、±dp/dt_(max)、HO-1、脂联素水平明显降低(P<0.05,P<0.01)。结论L-4F通过激活肥胖合并心肌梗死大鼠HO-1-脂联素轴,抑制内质网应激,降低心肌细胞毒性,抑制心脏重构,改善大鼠心功能。
基金supported by a grant from the Military "Twelve Five-Year Project"of China(No.CWS12J122)
文摘This study was aimed to investigate the effect of stress induced by high-intensity exercises on the cardiovascular system. In the epidemiological investigation, 200 subjects（test group） engaged in special high-intensity exercises, and 97 who lived and worked in the same environment and conditions as those in the test group, but did not participate in the exercises served as controls. In the second part of the study, 50 mice were randomly divided into control group, exhaustive swimming group, white noise group, exhaustive swimming plus white noise group, and pioglitazone intervention group. The results showed that the plasma concentrations of the myocardial injury markers heart fatty acid-binding protein（H-FABP）, C-reactive protein（CRP）, β-endorphin（β-EP） and levels of psychological stress were significantly increased in test group as compared with control group; special high-intensity exercises resulted in a significant elevation of the incidence of cardiac arrhythmias. Animal experiments showed that the plasma levels of corticosterone（CORT） and troponin I（Tn I） were raised while the level of SOD was reduced in exhaustive swimming group, white noise group, and exhaustive swimming plus white noise group. The expression levels of PPARγ m RNA and protein were decreased in myocardial tissues in these groups as well. HE staining showed no remarkable change in myocardial tissues in all the groups. Treatment with pioglitazone significantly decreased the plasma levels of Tn I and CORT, while increased the level of SOD and the expression levels of PPARγ m RNA and protein. It was concluded that the high-intensity exercises may induce a heavy physical and psychological stress and predispose the subjects to accumulated fatigue and sleep deprivation; high-intensity exercises also increases the incidence of arrhythmias and myocardial injury. PPARγ may be involved in the physical and psychological changes induced by high-intensity exercises.
