期刊
CIRCULATION JOURNAL
卷 78, 期 12, 页码 2979-2986出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-14-0521
关键词
Coronary flow reserve; Diabetes; FTY720; Microcirculation; Sphingosine-1-phosphate
资金
- Key Laboratory of Nuclear Medicine, Ministry of Health
- Jiangsu Key Laboratory of Molecular Nuclear Medicine [KF201302]
Background: Impairment of coronary flow reserve (CFR) has been generally demonstrated in diabetic patients and animals with microvascular complications but without obvious obstructive coronary atherosclerosis. There have been few studies investigating CFR in cases of relatively well-controlled therapy. The purpose of this study is to evaluate the effect of treatment with a Sphingosine-1-phosphate (S1P) receptor potent agonist, FTY720, on early diabetic rats in terms of CFR. Methods and Results: Male Sprague-Dawley (SD) rats were divided into 3 groups: (1) streptozotocin-uninjected rats (control rats); (2) streptozotocin-injected hyperglycemic rats (diabetic group); and (3) FTY720-fed and streptozotocin-injected hyperglycemic rats. FTY720 (1.25 mg/kg per day orally) was administrated for 9 weeks in SD rats (from 6 weeks old to 15 weeks old). CFR was evaluated by (NH3)-N-13-positron emission tomography. No obvious pathological changes of macrovascular atherosclerosis were observed in each group. Diabetic rats had impaired CFR compared with the control group (1.39+/-0.26 vs. 1.94+/-0.24, P<0.05). Treatment with FTY720 for 9 weeks attenuated the heart histological changes and improved CFR in 32% of diabetic rats (1.84+/-0.36 vs. 1.39+/-0.26, P<0.05). Conclusions: In summary, long-term therapy with the Sphingosine-1-phosphate receptor agonist, FTY720, improved CFR by attenuating the heart histological changes, and it might have a beneficial effect on coronary microvascular function in diabetic rats.
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