García-Pedraza José-Ángel, Ferreira-Santos Pedro, Aparicio Rubén, Montero María-José, Morán Asunción
Laboratory of Pharmacology, Department of Physiology and Pharmacology, Faculty of Pharmacy, University of Salamanca, 37007, Salamanca, Spain.
Biomedical Research Institute of Salamanca (IBSAL), University Hospital of Salamanca-USAL- CSIC, Salamanca, Spain.
Sci Rep. 2016 Sep 23;6:33979. doi: 10.1038/srep33979.
This study aimed to determine whether the serotonergic modulation, through selective 5-HT receptor blockade, restores cardiovascular disturbances in type 1 diabetic rats. Diabetes was induced by alloxan (150 mg/kg, s.c.) and maintained for 4 weeks. 5-HT receptor was blocked by sarpogrelate (30 mg/kg.day; 14 days; p.o.). Systolic blood pressure (SBP), heart rate (HR), glycaemia and body weight (BW) were monitored periodically. Animals were sacrificed at the end of the study and the heart, right kidney and thoracic aorta were removed; plasma samples were also obtained. Left ventricular hypertrophy index (LVH) and renal hypertrophy index (RH) were determined. Vascular function was studied in aorta rings; additionally, superoxide anion (O•) production (by lucigenin-enhanced chemiluminescence) and lipid peroxidation (by thiobarbituric acid reactive substances assay) were measured. Neither alloxan nor sarpogrelate treatments altered HR, LVH or endothelium-independent relaxation. SBP, glycaemia, BW, RH, O• production and lipid peroxidation were significantly altered in diabetic animals compared with controls. Sarpogrelate treatment considerably decreased SBP, RH, O• production and lipid peroxidation. Endothelium-dependent relaxation was severely reduced in diabetic animal aortas compared to controls; sarpogrelate treatment markedly improved it. Our outcomes show that selectively blocking 5-HT receptors has beneficial effects on impaired cardiovascular parameters in diabetes.
本研究旨在确定通过选择性5-羟色胺（5-HT）受体阻断进行的5-羟色胺能调节是否能恢复1型糖尿病大鼠的心血管紊乱。用四氧嘧啶（150mg/kg，皮下注射）诱导糖尿病并维持4周。用沙格雷酯（30mg/kg·天；14天；口服）阻断5-HT受体。定期监测收缩压（SBP）、心率（HR）、血糖和体重（BW）。在研究结束时处死动物，取出心脏、右肾和胸主动脉；还获取血浆样本。测定左心室肥厚指数（LVH）和肾肥厚指数（RH）。在主动脉环中研究血管功能；此外，测量超氧阴离子（O•）生成（通过光泽精增强化学发光法）和脂质过氧化（通过硫代巴比妥酸反应性物质测定法）。四氧嘧啶和沙格雷酯治疗均未改变HR、LVH或非内皮依赖性舒张。与对照组相比，糖尿病动物的SBP、血糖、BW、RH、O•生成和脂质过氧化有显著改变。沙格雷酯治疗显著降低了SBP、RH、O•生成和脂质过氧化。与对照组相比，糖尿病动物主动脉的内皮依赖性舒张严重降低；沙格雷酯治疗显著改善了这一情况。我们的结果表明，选择性阻断5-HT受体对糖尿病受损的心血管参数有有益影响。
