沙格雷酯治疗2型糖尿病伴下肢动脉硬化闭塞症患者的疗效评估

目的:探讨沙格雷酯治疗2型糖尿病伴下肢动脉硬化闭塞症(ASO)患者的临床疗效。方法:选择2014年4月~2015年5月我院2型糖尿病伴下肢ASO患者80例,给予口服沙格雷酯100 mg,3次/日,连续8周,监测治疗前后患肢的症状与体征、双下肢动脉峰值血流速度、血糖、血脂及血液流变学等指标的变化。结果:口服沙格雷酯8周后,患者疼痛感、冷感、间歇性踱行、麻木感及下肢溃疡等主观症状有效率均大于91%,临床总有效率为93.75%。治疗后患者左、右下肢动脉血管直径与治疗前比较,差异无统计学意义(P0.05),但左、右下肢动脉峰值血流速度比治疗前显著降低,差异有统计学意义(P0.05)。治疗后患者的甘油三酯、总胆固醇、低密度脂蛋白、全血高切黏度及全血低切黏度比治疗前降低,差异有统计学意义(P0.05)。结论:沙格雷酯可改善2型糖尿病伴下肢ASO患者的症状,降低双下肢动脉峰值血流速度,临床疗效确切,值得临床推广应用。     

5-HT2 receptor blocker sarpogrelate prevents downregulation of antiapoptotic protein Bcl-2 and protects the heart against ischemia-reperfusion injury

Even though reperfusion is the treatment of choice in patients admitted with acute myocardial infarction, reperfusion itself has been demonstrated to activate various pathological factors especially following procedures of cardiac revascularization. 5-hydroxytryptamine (5HT) is one such factor activated during reperfusion and is known to trigger the post ischemic contractile dysfunction and pathological apoptosis. Here we demonstrate the potential effects of the 5-HT(2)A antagonist sarpogrelate in protecting the myocardium against reperfusion injury of heart. Male Wistar rats weighing between 220 and 240 g were subjected to 30 min left coronary artery (LCA) occlusion and 120 min reperfusion. Sarpogrelate (4 mg/kg) was infused intravenously for 30 min either before LCA occlusion or at reperfusion. Following reperfusion the samples were collected for infarction area, immunohistochemistry, western blotting and myocardial metabolite analysis. Sarpogrelate infusion before ischemia resulted in (a) significant recovery of post ischemic cardiac functions (LVDP, EDP), (b) significant reduction in the infarct size among the risk area after triphenyl tetrazolium chloride staining (p<0.001), (c) decreased tissue water content (p<0.05), (d) well preserved myocardial ATP (p<0.05), (e) reduction in Bcl-2 downregulation and caspase 3 activation and (g) less prevalence of apoptotic cells (3.1+/-0.4% to 15.2+/-0.6%, drug versus control). Treating the rats with sarpogrelate during reperfusion also showed similar results. This study thus demonstrates the protective effects of sarpogrelate and supports the role for 5-HT2A inhibition in preventing the reperfusion injury of the heart.     

5-Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue

Knowledge of the regulatory factors associated with down-regulation of adiponectin gene expression and up-regulation of PAI-1 gene expression is crucial to understand the pathophysiological basis of obesity and metabolic diseases, and could establish new treatment strategies for these conditions. We showed that expression of 5-HT(2A) receptors was up-regulated in hypertrophic 3T3-L1 adipocytes, which exhibited decreased expression of adiponectin and increased expression of PAI-1. 5-HT(2A) receptor antagonists and suppression of 5-HT(2A) receptor gene expression enhanced adiponectin expression. Activation of Gq negatively regulated adiponectin expression, and inhibition of mitogen-activated protein kinase reversed the Gq-induced effect. Moreover, the 5-HT(2A) receptor blockade reduced PAI-1 expression. These findings indicate that antagonism of 5-HT(2A) receptors in adipocytes could improve the obesity-linked decreases in adiponectin expression and increases in PAI-1 expression.