目的:探讨人urotensinⅡ(h UⅡ)抗大鼠心肌缺血再灌注损伤的作用机制。方法:在大鼠冠状动脉左前降支结扎再灌注模型上,观察心电图变化,测定心肌梗死体积及心肌组织中诱导型一氧化氮合酶(inducible NO synthesis,i NOS)mRNA表达。结果:0...目的:探讨人urotensinⅡ(h UⅡ)抗大鼠心肌缺血再灌注损伤的作用机制。方法:在大鼠冠状动脉左前降支结扎再灌注模型上,观察心电图变化,测定心肌梗死体积及心肌组织中诱导型一氧化氮合酶(inducible NO synthesis,i NOS)mRNA表达。结果:0.47、1.4和4.2μg/kg h UⅡ可明显抑制缺血再灌注损伤大鼠心电图ST段抬高和心肌梗死体积;4.2μg/kg h UⅡ显著地改善冠状动脉结扎再灌注大鼠心肌细胞超微结构的变化,并增强大鼠心肌组织中i NOS mRNA表达;urotensinⅡ受体(UT)拮抗剂urantide 10 nmol/kg可明显地拮抗1.4和4.2μg/kg h UII对缺血再灌注大鼠心电图ST段抬高和心肌梗死的抑制作用。结论:HUII抗大鼠心肌缺血性损伤作用可能与激动UT及促进NO合成有关。展开更多
AIM: To investigated the effects of urotensin Ⅱ(UII) on hepatic insulin resistance in Hep G2 cells and the potential mechanisms involved.METHODS: Human hepatoma Hep G2 cells were cultured with or without exogenous UI...AIM: To investigated the effects of urotensin Ⅱ(UII) on hepatic insulin resistance in Hep G2 cells and the potential mechanisms involved.METHODS: Human hepatoma Hep G2 cells were cultured with or without exogenous UII for 24 h, in the presence or absence of 100 nmol/L insulin for the last 30 min. Glucose levels were detected by the glucoseoxidase method and glycogen synthesis was analyzed by glycogen colorimetric/fluorometric assay. Reactive oxygen species(ROS) levels were detected with a multimode reader using a 2′,7′-dichlorofluorescein diacetate probe. The protein expression and phosphorylation levels of c-Jun N-terminal kinase(JNK), insulin signal essential molecules such as insulin receptor substrate-1(IRS-1), protein kinase B(Akt), glycogen synthase kinase-3β(GSK-3β), and glucose transporter-2(Glut 2), and NADPH oxidase subunits such as gp91 phox, p67 phox, p47 phox, p40 phox, and p22 phox were evaluated by Western blot.RESULTS: Exposure to 100 nmol/L UII reduced the insulin-induced glucose consumption(P < 0.05)and glycogen content(P < 0.01) in Hep G2 cells compared with cells without UII. UII also abolished insulin-stimulated protein expression(P < 0.01) and phosphorylation of IRS-1(P < 0.05), associated with down-regulation of Akt(P < 0.05) and GSK-3β(P < 0.05) phosphorylation levels, and the expression of Glut 2(P < 0.001), indicating an insulin-resistance state in Hep G2 cells. Furthermore, UII enhanced the phosphorylation of JNK(P < 0.05), while the activity of JNK, insulin signaling, such as total protein of IRS-1(P < 0.001), phosphorylation of IRS-1(P < 0.001) and GSK-3β(P < 0.05), and glycogen synthesis(P < 0.001) could be reversed by pretreatment with the JNK inhibitor SP600125. Besides, UII markedly improved ROS generation(P < 0.05) and NADPH oxidase subunit expression(P < 0.05). However, the antioxidant/NADPH oxidase inhibitor apocynin could decrease UII-induced ROS production(P < 0.05), JNK phosphorylation(P < 0.05), and insulin resistance(P < 0.05) in HepG 2 cells. CONCLUSION: UII induces insulin resistance, and this can be reversed by JNK inhibitor SP600125 and antioxidant/NADPH oxidase inhibitor apocynin targeting the insulin signaling pathway in HepG 2 cells.展开更多
BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent v...BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies.展开更多
Objective To determine the plasma urolensin Ⅱ(UII) levels in various types of coronary heart disease and to clarify how the plasma UII levels correlate with the clinical presentation, extent and severity of coronary ...Objective To determine the plasma urolensin Ⅱ(UII) levels in various types of coronary heart disease and to clarify how the plasma UII levels correlate with the clinical presentation, extent and severity of coronary artery atherosclerosis (CAD). Methods: One hundred and three aged patients undergoing elective diagnostic coronary angiography for proven or clinical suspected coronary heart disease were enrolled in this study. The extent and severity of coronary artery disease were evaluated by vessel score and Gensini score, respectively. Plasma UII levels were measured by radioimmunoassay. Results: The plasma UII levels in the patients with modest to severe coronary stenosis (3.03±0.34 pg/ml, 1.83±0.67 pg/ml) were significantly lower than that in subjects with normal coronary artery (4.80±1.11 pg/ml, P<0.001). The plasma UII levels in patients with coronary heart disease were also significantly lower than that in patients with insignificant coronary stenosis (P < 0. 001). Compared to patients with stable angina pectoris, plasma UII levels in patients with acute coronary syndrome were significantly decreased (1.89±0.51 pg/ml vs 2.42±0.77 pg/ml, P < 0.001). Plasma UII levels were found to be negatively correlated with the severity of coronary artery stenosis (r = -0.488, P<0.001), as well as the vessel score (r = -0.408, P<0.05) in the patients with CAD. Conclusion: Significant inverse correlations exist between the plasma UII levels, and the extent and severity of coronary artery stenosis. These findings suggest that plasma UII contribute to the development and progression of coronary artery stenosis, and may be a novel marker to predict clinical types, as well as the extent and severity of coronary artery disease in the patients.展开更多
Objective The goal of this study was to examine the association between urotensin Ⅱ (U Ⅱ) concentration and the severity of coronary artery disease (CAD). Methods We studied U Ⅱ concentrations in 100 patients with ...Objective The goal of this study was to examine the association between urotensin Ⅱ (U Ⅱ) concentration and the severity of coronary artery disease (CAD). Methods We studied U Ⅱ concentrations in 100 patients with known or suspected CAD referred for cardiac catheterization. Based on coronary angiograms, subjects were classified as having no or mild CAD (stenosis <50%) and significant CAD (stenosis=50%). Micheal score system was used to estimate the severity of CAD. Result U Ⅱ concentration in the significant CAD group had no difference compared with the no or mild CAD group (1.95±1.18pmol/L vs 2.04±1.47pmol/L, P>0.05), but higher in the severe group (score =9) than in the normal or nearly normal group (score<3)(2.50±1.62pmol/L vs 1.61±1.05pmol/L, P=0.03). UⅡ concentration had no relationship with other known risk factors, but it correlated with CAD severity (r=0.213, P=0.034). In multiple regression analysis, U Ⅱ is one of the determinants of the severity of CAD, other than age, abnormal glucose, hypertension and gender. Conclusios U Ⅱ is elevated in severe CAD and there is a significant relationship between U Ⅱ concentration and CAD severity. (J Geriatr Cardiol 2007;4:229-232.)展开更多
文摘目的:探讨人urotensinⅡ(h UⅡ)抗大鼠心肌缺血再灌注损伤的作用机制。方法:在大鼠冠状动脉左前降支结扎再灌注模型上,观察心电图变化,测定心肌梗死体积及心肌组织中诱导型一氧化氮合酶(inducible NO synthesis,i NOS)mRNA表达。结果:0.47、1.4和4.2μg/kg h UⅡ可明显抑制缺血再灌注损伤大鼠心电图ST段抬高和心肌梗死体积;4.2μg/kg h UⅡ显著地改善冠状动脉结扎再灌注大鼠心肌细胞超微结构的变化,并增强大鼠心肌组织中i NOS mRNA表达;urotensinⅡ受体(UT)拮抗剂urantide 10 nmol/kg可明显地拮抗1.4和4.2μg/kg h UII对缺血再灌注大鼠心电图ST段抬高和心肌梗死的抑制作用。结论:HUII抗大鼠心肌缺血性损伤作用可能与激动UT及促进NO合成有关。
基金Supported by National Natural Science Foundation of China,No.81272757the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges under Beijing Municipality,No.IDHT20150502
文摘AIM: To investigated the effects of urotensin Ⅱ(UII) on hepatic insulin resistance in Hep G2 cells and the potential mechanisms involved.METHODS: Human hepatoma Hep G2 cells were cultured with or without exogenous UII for 24 h, in the presence or absence of 100 nmol/L insulin for the last 30 min. Glucose levels were detected by the glucoseoxidase method and glycogen synthesis was analyzed by glycogen colorimetric/fluorometric assay. Reactive oxygen species(ROS) levels were detected with a multimode reader using a 2′,7′-dichlorofluorescein diacetate probe. The protein expression and phosphorylation levels of c-Jun N-terminal kinase(JNK), insulin signal essential molecules such as insulin receptor substrate-1(IRS-1), protein kinase B(Akt), glycogen synthase kinase-3β(GSK-3β), and glucose transporter-2(Glut 2), and NADPH oxidase subunits such as gp91 phox, p67 phox, p47 phox, p40 phox, and p22 phox were evaluated by Western blot.RESULTS: Exposure to 100 nmol/L UII reduced the insulin-induced glucose consumption(P < 0.05)and glycogen content(P < 0.01) in Hep G2 cells compared with cells without UII. UII also abolished insulin-stimulated protein expression(P < 0.01) and phosphorylation of IRS-1(P < 0.05), associated with down-regulation of Akt(P < 0.05) and GSK-3β(P < 0.05) phosphorylation levels, and the expression of Glut 2(P < 0.001), indicating an insulin-resistance state in Hep G2 cells. Furthermore, UII enhanced the phosphorylation of JNK(P < 0.05), while the activity of JNK, insulin signaling, such as total protein of IRS-1(P < 0.001), phosphorylation of IRS-1(P < 0.001) and GSK-3β(P < 0.05), and glycogen synthesis(P < 0.001) could be reversed by pretreatment with the JNK inhibitor SP600125. Besides, UII markedly improved ROS generation(P < 0.05) and NADPH oxidase subunit expression(P < 0.05). However, the antioxidant/NADPH oxidase inhibitor apocynin could decrease UII-induced ROS production(P < 0.05), JNK phosphorylation(P < 0.05), and insulin resistance(P < 0.05) in HepG 2 cells. CONCLUSION: UII induces insulin resistance, and this can be reversed by JNK inhibitor SP600125 and antioxidant/NADPH oxidase inhibitor apocynin targeting the insulin signaling pathway in HepG 2 cells.
文摘BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies.
文摘Objective To determine the plasma urolensin Ⅱ(UII) levels in various types of coronary heart disease and to clarify how the plasma UII levels correlate with the clinical presentation, extent and severity of coronary artery atherosclerosis (CAD). Methods: One hundred and three aged patients undergoing elective diagnostic coronary angiography for proven or clinical suspected coronary heart disease were enrolled in this study. The extent and severity of coronary artery disease were evaluated by vessel score and Gensini score, respectively. Plasma UII levels were measured by radioimmunoassay. Results: The plasma UII levels in the patients with modest to severe coronary stenosis (3.03±0.34 pg/ml, 1.83±0.67 pg/ml) were significantly lower than that in subjects with normal coronary artery (4.80±1.11 pg/ml, P<0.001). The plasma UII levels in patients with coronary heart disease were also significantly lower than that in patients with insignificant coronary stenosis (P < 0. 001). Compared to patients with stable angina pectoris, plasma UII levels in patients with acute coronary syndrome were significantly decreased (1.89±0.51 pg/ml vs 2.42±0.77 pg/ml, P < 0.001). Plasma UII levels were found to be negatively correlated with the severity of coronary artery stenosis (r = -0.488, P<0.001), as well as the vessel score (r = -0.408, P<0.05) in the patients with CAD. Conclusion: Significant inverse correlations exist between the plasma UII levels, and the extent and severity of coronary artery stenosis. These findings suggest that plasma UII contribute to the development and progression of coronary artery stenosis, and may be a novel marker to predict clinical types, as well as the extent and severity of coronary artery disease in the patients.
文摘Objective The goal of this study was to examine the association between urotensin Ⅱ (U Ⅱ) concentration and the severity of coronary artery disease (CAD). Methods We studied U Ⅱ concentrations in 100 patients with known or suspected CAD referred for cardiac catheterization. Based on coronary angiograms, subjects were classified as having no or mild CAD (stenosis <50%) and significant CAD (stenosis=50%). Micheal score system was used to estimate the severity of CAD. Result U Ⅱ concentration in the significant CAD group had no difference compared with the no or mild CAD group (1.95±1.18pmol/L vs 2.04±1.47pmol/L, P>0.05), but higher in the severe group (score =9) than in the normal or nearly normal group (score<3)(2.50±1.62pmol/L vs 1.61±1.05pmol/L, P=0.03). UⅡ concentration had no relationship with other known risk factors, but it correlated with CAD severity (r=0.213, P=0.034). In multiple regression analysis, U Ⅱ is one of the determinants of the severity of CAD, other than age, abnormal glucose, hypertension and gender. Conclusios U Ⅱ is elevated in severe CAD and there is a significant relationship between U Ⅱ concentration and CAD severity. (J Geriatr Cardiol 2007;4:229-232.)
