Arterial pressure labiality is improved by sodium-glucose cotransporter 2 inhibitor in streptozocin-induced diabetic rats.
Arterial pressure labiality is improved by sodium-glucose cotransporter 2 inhibitor in streptozocin-induced diabetic rats.
复制标题
钠-葡萄糖协同转运蛋白 2 抑制剂可改善链佐星诱导的糖尿病大鼠的动脉压唇侧。
DOI：
10.1038/hr.2017.14
复制
发表时间：
2017
期刊：
影响因子：
5.4
通讯作者：
Hirooka Y.
中科院分区：
文献类型：
--
作者：
Yoshikawa T;Kishi T;Sahinohara K;Takesue K;Shibata R;Inoguchi T;Sunagawa K;Tsutsui H;Hirooka Y.
为了预防糖尿病（DM）患者的心血管事件，降低动脉压（AP）是必不可少的。钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）通过糖尿病患者的抑制反应来预防心血管事件。在本研究中，我们研究了SGLT2i是否能改善糖尿病大鼠的AP敏感性。10周龄雄性Sprague-Dawley大鼠单次静脉注射链脲佐菌素（50 mg kg - 1），分为3组，分别给予低剂量SGLT2i、载药（VEH）或皮下植入胰岛素微丸（SGLT2i、VEH和胰岛素组），疗程14 d。SGLT2i降低血糖，但效果低于胰岛素。实验结束时，SGLT2i组、胰岛素组和VEH组的遥测平均AP无差异（分别为83±7 vs 98±9 vs 90±8 mm Hg， n= 5）。活动性指标AP的标准差SGLT2i组明显小于VEH组（5.6±0.5 vs 7.0±0.7 mm Hg, n= 5， P< 0.05）。SGLT2i组活跃期交感神经活动明显低于VEH组。SGLT2i组的压力反射敏感性（BRS）明显高于VEH组。胰岛素组和VEH组间AP和交感神经兴奋的标准差无差异。综上所述，非抑制剂量的SGLT2i改善了与交感神经抑制相关的活动性，改善了链脲佐菌素诱导的DM大鼠的BRS。
To prevent cardiovascular events in patients with diabetes mellitus (DM), it is essential to reduce arterial pressure (AP). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) prevents cardiovascular events via the depressor response in patients with DM. In the present study, we examined whether SGLT2i ameliorates AP lability in DM rats. Ten-week-old male Sprague–Dawley rats were administered a single intravenous injection of streptozotocin (50 mg kg− 1) and were divided into three groups treated with low-dose SGLT2i, vehicle (VEH) or subcutaneously implanted insulin pellets (SGLT2i, VEH and Insulin group, respectively) for 14 days. SGLT2i reduced blood glucose, but its effect was lower than that of insulin. The telemetered mean AP at the end of the experiment did not differ among the SGLT2i, Insulin and VEH groups (83±7 vs. 98±9 vs. 90±8 mm Hg, respectively, n= 5 for each). The standard deviation of AP as the index of lability was significantly smaller during the active period in the SGLT2i group than in the VEH group (5.6±0.5 vs. 7.0±0.7 mm Hg, n= 5 for each, P< 0.05). Sympathetic nerve activity during the active period was significantly lower in the SGLT2i group than in the VEH group. Baroreflex sensitivity (BRS) was significantly higher in the SGLT2i group than in the VEH group. The standard deviation of AP and sympathoexcitation did not differ between the Insulin and VEH groups. In conclusion, SGLT2i at a non-depressor dose ameliorated the AP lability associated with sympathoinhibition during the active period and improved the BRS in streptozotocin-induced DM rats.