Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failu...Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failure （HF）. Methods Rat models of I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF （HF, n = 16）, NRG-1β trealanent （NRG, n = 16）, and sham operation （S, n = 16） group. The rats in the NRG group were administered NRG-1β （10 μg/kg per day） for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline, Twelve weeks after operation, Connexin 43 （Cx43） expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.展开更多
目的探究皮层肌动蛋白结合蛋白(Cortactin)对异丙肾上腺素(isoprenaline,ISO)诱导的病理性心肌肥大的调控作用及其机制。方法采用ISO刺激新生大鼠心肌细胞(neonatal rat cardiomyocytes,NRCMs)24 h,在细胞水平建立心肌肥大模型;C57BL/6...目的探究皮层肌动蛋白结合蛋白(Cortactin)对异丙肾上腺素(isoprenaline,ISO)诱导的病理性心肌肥大的调控作用及其机制。方法采用ISO刺激新生大鼠心肌细胞(neonatal rat cardiomyocytes,NRCMs)24 h,在细胞水平建立心肌肥大模型;C57BL/6小鼠皮下注射ISO 1周,在动物水平建立心肌肥大模型。采用RT-qPCR检测mRNA的变化;免疫印迹法检测相应蛋白含量的变化;免疫荧光法检测Cortactin的亚细胞定位及表达量的变化;采用腺病毒感染的方法过表达Cortactin,通过转染小干扰RNA敲低Cortactin。结果在细胞和动物水平上,成功建立ISO诱导的心肌肥大模型,均观察到ISO引起Cortactin和N型钙黏连蛋白(N-cadherin)水平降低;过表达Cortactin可逆转ISO导致的N-cadherin蛋白水平的降低及心肌细胞肥大反应;敲低Cortactin则显示相反的效应。结论Cortactin可能联合N-cadherin通过增强心肌细胞之间的连接,发挥抗心肌肥大的作用。展开更多
AIM:To investigate the nature and origin of cardiac mucosa(CM).METHODS:Biopsy samples from sixty-one individuals were included in this study. The specimens were taken "at","just below",or "jus...AIM:To investigate the nature and origin of cardiac mucosa(CM).METHODS:Biopsy samples from sixty-one individuals were included in this study. The specimens were taken "at","just below",or "just above" the gastroesophageal junction,including the histologic squamocolumnar junction. Clinical data were obtained by reviewing electronic medical records for each patient. Patients with a history of stomach adenoma or carcinoma and esophageal carcinoma were excluded,and cases that were endoscopically suspicious of Barrett's esophagus or a polyp were also ruled out. Histologic and endoscopic reviews were performed blinded to the patient's clinical data. Histologic evaluation wasconducted by two pathologists,and endoscopic review was performed by a endoscopist with wide experience in the field. Histologically,the columnar epithelium of squamocolumnar junction,presence and severity of acute and chronic inflammation,atrophy,intestinal metaplasia,and presence of carditis were evaluated. Endoscopically,reflux esophagitis was evaluated by Los Angeles(LA) classification,hiatal hernias were classified by Hill grade,and gastroesophageal flap valves were assessed. RESULTS:Fifty-nine of the 61(96.7%) patients were Korean; 65.6%(40/61) of the patients underwent endoscopy according to the schedule of the National Health Insurance Program as a screening inspection. Of these,only 20.0%(8/40) of cases had reflux s y m p t o m s. C M w a s p r e s e n t i n 4 1 / 6 1( 6 7. 2 %) individuals,and its presence was associated with older age compared to oxyntocardiac mucosa/oxyntic mucosa(60.59 ± 2.02 years vs 51.55 ± 3.35 years; P = 0.018). The presence of CM was associated with endoscopic diagnosis of esophagitis according to the LA classification(P = 0.022). CM was associated with mononuclear cell infiltration and neutrophilic infiltration,which were statistically significant(P = 0.001,and P = 0.004,respectively). The inflammation of CM,"carditis",showed a statistically significant association with endoscopic diagnosis of reflux esophagitis展开更多
目的观察压力超负荷所致心力衰竭(HF)大鼠心室肌电生理失稳态和缝隙连接蛋白Cx43表达的变化。方法采用腹主动脉缩窄法建立压力超负荷大鼠HF模型,取左室舒张末压≥15mmHg的存活大鼠入HF组,另设假结扎对照组。术后32周两组大鼠以颈总动脉...目的观察压力超负荷所致心力衰竭(HF)大鼠心室肌电生理失稳态和缝隙连接蛋白Cx43表达的变化。方法采用腹主动脉缩窄法建立压力超负荷大鼠HF模型,取左室舒张末压≥15mmHg的存活大鼠入HF组,另设假结扎对照组。术后32周两组大鼠以颈总动脉插管法和心脏B超测定心功能,并检测电生理指标,以免疫印迹方法检测心肌细胞Cx43蛋白表达的变化,通过透射电镜观察心室肌缝隙连接分布的变化。结果 HF大鼠出现明显电生理失稳态和心功能不全,左室舒张末压明显增高而心室有效不应期明显延长,左室射血分数明显下降,同时大鼠心室肌中缝隙连接蛋白Cx43表达明显下调(0.929±0.095 vs 1.250±0.083,P<0.05)并出现空间重构。结论压力超负荷所致HF大鼠心室肌存在明显缝隙连接重构,这可能是导致HF时心肌电生理重构的重要机制。展开更多
基金This research was supported by the Key Program，the National Natural Science Foundation of China
文摘Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failure （HF）. Methods Rat models of I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF （HF, n = 16）, NRG-1β trealanent （NRG, n = 16）, and sham operation （S, n = 16） group. The rats in the NRG group were administered NRG-1β （10 μg/kg per day） for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline, Twelve weeks after operation, Connexin 43 （Cx43） expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.
文摘目的探究皮层肌动蛋白结合蛋白(Cortactin)对异丙肾上腺素(isoprenaline,ISO)诱导的病理性心肌肥大的调控作用及其机制。方法采用ISO刺激新生大鼠心肌细胞(neonatal rat cardiomyocytes,NRCMs)24 h,在细胞水平建立心肌肥大模型;C57BL/6小鼠皮下注射ISO 1周,在动物水平建立心肌肥大模型。采用RT-qPCR检测mRNA的变化;免疫印迹法检测相应蛋白含量的变化;免疫荧光法检测Cortactin的亚细胞定位及表达量的变化;采用腺病毒感染的方法过表达Cortactin,通过转染小干扰RNA敲低Cortactin。结果在细胞和动物水平上,成功建立ISO诱导的心肌肥大模型,均观察到ISO引起Cortactin和N型钙黏连蛋白(N-cadherin)水平降低;过表达Cortactin可逆转ISO导致的N-cadherin蛋白水平的降低及心肌细胞肥大反应;敲低Cortactin则显示相反的效应。结论Cortactin可能联合N-cadherin通过增强心肌细胞之间的连接,发挥抗心肌肥大的作用。
基金Supported by A grant from the National R and D Program for Cancer Control,Ministry for Health,Welfare,and Family affairs,South Korea,No.0920050
文摘AIM:To investigate the nature and origin of cardiac mucosa(CM).METHODS:Biopsy samples from sixty-one individuals were included in this study. The specimens were taken "at","just below",or "just above" the gastroesophageal junction,including the histologic squamocolumnar junction. Clinical data were obtained by reviewing electronic medical records for each patient. Patients with a history of stomach adenoma or carcinoma and esophageal carcinoma were excluded,and cases that were endoscopically suspicious of Barrett's esophagus or a polyp were also ruled out. Histologic and endoscopic reviews were performed blinded to the patient's clinical data. Histologic evaluation wasconducted by two pathologists,and endoscopic review was performed by a endoscopist with wide experience in the field. Histologically,the columnar epithelium of squamocolumnar junction,presence and severity of acute and chronic inflammation,atrophy,intestinal metaplasia,and presence of carditis were evaluated. Endoscopically,reflux esophagitis was evaluated by Los Angeles(LA) classification,hiatal hernias were classified by Hill grade,and gastroesophageal flap valves were assessed. RESULTS:Fifty-nine of the 61(96.7%) patients were Korean; 65.6%(40/61) of the patients underwent endoscopy according to the schedule of the National Health Insurance Program as a screening inspection. Of these,only 20.0%(8/40) of cases had reflux s y m p t o m s. C M w a s p r e s e n t i n 4 1 / 6 1( 6 7. 2 %) individuals,and its presence was associated with older age compared to oxyntocardiac mucosa/oxyntic mucosa(60.59 ± 2.02 years vs 51.55 ± 3.35 years; P = 0.018). The presence of CM was associated with endoscopic diagnosis of esophagitis according to the LA classification(P = 0.022). CM was associated with mononuclear cell infiltration and neutrophilic infiltration,which were statistically significant(P = 0.001,and P = 0.004,respectively). The inflammation of CM,"carditis",showed a statistically significant association with endoscopic diagnosis of reflux esophagitis
文摘目的观察压力超负荷所致心力衰竭(HF)大鼠心室肌电生理失稳态和缝隙连接蛋白Cx43表达的变化。方法采用腹主动脉缩窄法建立压力超负荷大鼠HF模型,取左室舒张末压≥15mmHg的存活大鼠入HF组,另设假结扎对照组。术后32周两组大鼠以颈总动脉插管法和心脏B超测定心功能,并检测电生理指标,以免疫印迹方法检测心肌细胞Cx43蛋白表达的变化,通过透射电镜观察心室肌缝隙连接分布的变化。结果 HF大鼠出现明显电生理失稳态和心功能不全,左室舒张末压明显增高而心室有效不应期明显延长,左室射血分数明显下降,同时大鼠心室肌中缝隙连接蛋白Cx43表达明显下调(0.929±0.095 vs 1.250±0.083,P<0.05)并出现空间重构。结论压力超负荷所致HF大鼠心室肌存在明显缝隙连接重构,这可能是导致HF时心肌电生理重构的重要机制。
