目的:探讨小檗碱对缺血性脑梗死大鼠氧化应激/炎症反应、血管生成的作用。方法:选取60只SPF级SD大鼠,随机分为对照组、模型组和小檗碱组各20只。建立大鼠脑缺血再灌注损伤模型。术后及给药后7d采用Longa标准评分评估大鼠神经功能。检测...目的:探讨小檗碱对缺血性脑梗死大鼠氧化应激/炎症反应、血管生成的作用。方法:选取60只SPF级SD大鼠,随机分为对照组、模型组和小檗碱组各20只。建立大鼠脑缺血再灌注损伤模型。术后及给药后7d采用Longa标准评分评估大鼠神经功能。检测各组大鼠脑组织的抗氧化活性和炎症因子水平。采用免疫组化检测脑缺血再灌注皮质微血管密度(MVD)。采用实时定量聚合酶链反应(qRT-PCR)检测低氧诱导生长因子-1(HIF-1)和血管内皮生长因子(VEGF)m RNA表达水平。采用蛋白免疫印迹试验检测VEGF和HIF-1蛋白表达水平。结果:模型组和小檗碱组大鼠术后具有神经功能缺损症状表现,Longa评分均高于对照组。给药7 d后,模型组和小檗碱组大鼠Longa评分均高于对照组(P<0.05),且小檗碱组大鼠Longa评分低于模型组(P<0.05)。与对照组比较,模型组丙二醛(MDA)水平显著升高,而谷胱甘肽过氧化物酶(GSH-Px)和超氧化物岐化酶(SOD)活性显著降低(P<0.05)。与模型组比较,小檗碱组MDA水平显著降低,而GSH-Px和SOD活性显著升高(P<0.05)。与对照组比较,模型组白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平显著升高(P<0.05)。与模型组比较,小檗碱组IL-1β、TNF-α水平显著降低,差异有统计学意义(P<0.05)。给药7d后,模型组和小檗碱组MVD、VEGFm RNA和HIF-1 m RNA表达水平均高于对照组(P<0.05),而小檗碱组MVD、VEGF m RNA和HIF-1 m RNA表达水平高于模型组(P<0.05)。给药7 d后,小檗碱组和模型组VEGF和HIF-1蛋白表达水平均高于对照组(P<0.05),而小檗碱组VEGF和HIF-1蛋白表达水平高于模型组(P<0.05)。结论:小檗碱通过抑制氧化应激/炎症反应、促进血管生成从而达到脑保护作用,其机制可能与激活HIF-1/VEGF信号通路有关。展开更多
Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endot...Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2＋-activated K＋ （BK） channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents （defined as the iberiotoxin-sensitive K＋ component） contribute （65＋4）% of the total K＋currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2＋ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 （a specific BK channel i~ subunit activator） robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2＋ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2＋. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2＋ concentration of coronary arterial smooth muscle cells was increased from （103±23） nmol/L （n=5） of control rats to （193±22） nmol/L （n=6, P 〈0.05） of STZ-induced diabetic rats, reduced BK-β1 expression made these channels less sensitive to intracellular Ca2＋, which in turn led to enhanced smooth muscle contraction. Conclusions Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-β1 expression and reduction of the β1-mediated BK channel activation in diabetic vessels.展开更多
Background It is welt known that increased cumulative ventricular pacing proportion （CumVP%） is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatmen...Background It is welt known that increased cumulative ventricular pacing proportion （CumVP%） is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatment issue in recent years. This study aimed to investigate the effects of different pacing algorithms on CumVP% in patients with pacemakers. Methods Pacemakers with three pacing algorithms, i.e., conventional dual chamber rate adaptive pacing （DDDR）, search atrioventricular conduction plus （SAV＋） and managed ventricular pacing （MVP）, were implanted in 42 patients including 41 with bradycardia arrhythmias and one with ventricular tachycardia. Pacemakers were programmed to work in conventional DDDR, SAV＋ and MVP during the follow-up periods of the first, the second and the third month. In each pacing algorithm, the time percentages of four pacing and sense status including atrial sense-ventricular sense （AS-VS）, atrial sense-ventricular pacing （AS-VP）, atrial pacing-ventricular sense （AP-VS） and atrial pacing-ventricular pacing （AP-VP） were calculated. Cumulative ventricular pacing proportions were compared in the three pacing algorithms in the first, the second and the third month postoperatively. Results In the DDDR algorithm AS-VS, AS-VP, AP-VS and AP-VP were 2.4%, 52.3%, 2.5% and 42.8% respectively, while in SAV＋ they were 19.3%, 34.9%, 33.9% and 12.0%, in MVP they were 38.9%, 13.2%, 41.6% and 6.4%. In the above the DDDR, SAV＋ and MVP algorithms, cumulative ventricular pacing proportions were 95.1%, 46.9% and 19.6%, respectively （P〈0.05） and the percentages of CumVP% 〈40% in patients were 0, 23.8% and 95.2.0% （P〈0.05）. Conclusions Compared with the conventional DDDR algorithm, both SAY＋ and MVP significantly reduced the CumVP%, especially the MVP algorithm. Patients may benefit from MVP algorithm due to reduced CumVP%.展开更多
文摘目的:探讨小檗碱对缺血性脑梗死大鼠氧化应激/炎症反应、血管生成的作用。方法:选取60只SPF级SD大鼠,随机分为对照组、模型组和小檗碱组各20只。建立大鼠脑缺血再灌注损伤模型。术后及给药后7d采用Longa标准评分评估大鼠神经功能。检测各组大鼠脑组织的抗氧化活性和炎症因子水平。采用免疫组化检测脑缺血再灌注皮质微血管密度(MVD)。采用实时定量聚合酶链反应(qRT-PCR)检测低氧诱导生长因子-1(HIF-1)和血管内皮生长因子(VEGF)m RNA表达水平。采用蛋白免疫印迹试验检测VEGF和HIF-1蛋白表达水平。结果:模型组和小檗碱组大鼠术后具有神经功能缺损症状表现,Longa评分均高于对照组。给药7 d后,模型组和小檗碱组大鼠Longa评分均高于对照组(P<0.05),且小檗碱组大鼠Longa评分低于模型组(P<0.05)。与对照组比较,模型组丙二醛(MDA)水平显著升高,而谷胱甘肽过氧化物酶(GSH-Px)和超氧化物岐化酶(SOD)活性显著降低(P<0.05)。与模型组比较,小檗碱组MDA水平显著降低,而GSH-Px和SOD活性显著升高(P<0.05)。与对照组比较,模型组白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平显著升高(P<0.05)。与模型组比较,小檗碱组IL-1β、TNF-α水平显著降低,差异有统计学意义(P<0.05)。给药7d后,模型组和小檗碱组MVD、VEGFm RNA和HIF-1 m RNA表达水平均高于对照组(P<0.05),而小檗碱组MVD、VEGF m RNA和HIF-1 m RNA表达水平高于模型组(P<0.05)。给药7 d后,小檗碱组和模型组VEGF和HIF-1蛋白表达水平均高于对照组(P<0.05),而小檗碱组VEGF和HIF-1蛋白表达水平高于模型组(P<0.05)。结论:小檗碱通过抑制氧化应激/炎症反应、促进血管生成从而达到脑保护作用,其机制可能与激活HIF-1/VEGF信号通路有关。
基金the National Natural Science Foundation of China，Natural Science Foundation of Jiangsu Province，Medical Key Personnel of Jiangsu Province，Top Qualified Personnel in Six Fields of Jiangsu Province (006) to WANG Ru-xing and the American Diabetes Association Junior Faculty Awards
文摘Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2＋-activated K＋ （BK） channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents （defined as the iberiotoxin-sensitive K＋ component） contribute （65＋4）% of the total K＋currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2＋ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 （a specific BK channel i~ subunit activator） robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2＋ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2＋. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2＋ concentration of coronary arterial smooth muscle cells was increased from （103±23） nmol/L （n=5） of control rats to （193±22） nmol/L （n=6, P 〈0.05） of STZ-induced diabetic rats, reduced BK-β1 expression made these channels less sensitive to intracellular Ca2＋, which in turn led to enhanced smooth muscle contraction. Conclusions Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-β1 expression and reduction of the β1-mediated BK channel activation in diabetic vessels.
文摘Background It is welt known that increased cumulative ventricular pacing proportion （CumVP%） is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatment issue in recent years. This study aimed to investigate the effects of different pacing algorithms on CumVP% in patients with pacemakers. Methods Pacemakers with three pacing algorithms, i.e., conventional dual chamber rate adaptive pacing （DDDR）, search atrioventricular conduction plus （SAV＋） and managed ventricular pacing （MVP）, were implanted in 42 patients including 41 with bradycardia arrhythmias and one with ventricular tachycardia. Pacemakers were programmed to work in conventional DDDR, SAV＋ and MVP during the follow-up periods of the first, the second and the third month. In each pacing algorithm, the time percentages of four pacing and sense status including atrial sense-ventricular sense （AS-VS）, atrial sense-ventricular pacing （AS-VP）, atrial pacing-ventricular sense （AP-VS） and atrial pacing-ventricular pacing （AP-VP） were calculated. Cumulative ventricular pacing proportions were compared in the three pacing algorithms in the first, the second and the third month postoperatively. Results In the DDDR algorithm AS-VS, AS-VP, AP-VS and AP-VP were 2.4%, 52.3%, 2.5% and 42.8% respectively, while in SAV＋ they were 19.3%, 34.9%, 33.9% and 12.0%, in MVP they were 38.9%, 13.2%, 41.6% and 6.4%. In the above the DDDR, SAV＋ and MVP algorithms, cumulative ventricular pacing proportions were 95.1%, 46.9% and 19.6%, respectively （P〈0.05） and the percentages of CumVP% 〈40% in patients were 0, 23.8% and 95.2.0% （P〈0.05）. Conclusions Compared with the conventional DDDR algorithm, both SAY＋ and MVP significantly reduced the CumVP%, especially the MVP algorithm. Patients may benefit from MVP algorithm due to reduced CumVP%.
