Ma Yu-Guang, Wang Jun-Wei, Bai Yun-Gang, Liu Mei, Xie Man-Jiang, Dai Zhi-Jun
Department of Oncology, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710004, China.
Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, China.
BMC Pharmacol Toxicol. 2017 Apr 26;18(1):30. doi: 10.1186/s40360-017-0135-8.
Vascular disease is a common and often severe complication in diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the leading risk factors for vascular complications in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetic patients at the same time. Salidroside (SAL) is the major active ingredient derived from Rhodiola. Recently, it has been reported that SAL have an obvious hypoglycemic effect in diabetes and show a beneficial activity in diabetic vascular dysfunction. However, it remains unknown whether or not SAL treatment could directly reduce blood pressure in diabetes. Furthermore, it is not clear what is the molecular mechanism underlying the vascular protection of SAL treatment in diabetes.
Male diabetic Goto-Kakizaki (GK) and non-diabetic control Wistar-Kyoto (WKY) rats were administrated with different dosages of SAL (50, 100 and 200 mg/kg/day) for 4 weeks. Contractile responsiveness of cerebral artery to KCl or 5-HT was investigated by Pressure Myograph System. The activity of Ca channel was investigated by recording whole-cell currents, assessing the expressions of Ca channel α-subunit and its downstream kinase, MLCK, at protein or mRNA levels.
We showed that administration of 100 mg/kg/day SAL for 4 weeks not only lowered blood glucose, but also reduced blood pressure and alleviated cerebrovascular contractile activity in diabetic GK rats, which suggested that SAL treatment may provide a combinational therapy for lowering blood glucose and reducing blood pressure in diabetes at the same time. Furthermore, SAL treatment markedly inhibited the function and expression of Ca channel in cerebral VSMCs isolated from diabetic GK rats or when exposed to hyperglycemia condition, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes.
The present study provided evidences that SAL contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic GK rats by inhibition of Ca channel in smooth muscle cells, which may provide a novel approach to treat vascular complications in diabetic patients.
血管疾病是糖尿病常见且往往较为严重的并发症。高血糖和高血压被认为是糖尿病患者血管并发症的两大主要危险因素。然而，很少有药物能够同时为糖尿病患者提供控制高血糖和血压的联合治疗。红景天苷（SAL）是从红景天中提取的主要活性成分。最近，有报道称SAL在糖尿病中具有明显的降血糖作用，并对糖尿病血管功能障碍显示出有益作用。然而，SAL治疗是否能直接降低糖尿病患者的血压仍不清楚。此外，SAL治疗在糖尿病中发挥血管保护作用的分子机制也尚不明确。
将雄性糖尿病Goto-Kakizaki（GK）大鼠和非糖尿病对照Wistar-Kyoto（WKY）大鼠给予不同剂量的SAL（50、100和200mg/kg/天），持续4周。通过压力肌动描记系统研究脑动脉对氯化钾或5-羟色胺的收缩反应性。通过记录全细胞电流、评估钙通道α亚基及其下游激酶肌球蛋白轻链激酶（MLCK）在蛋白质或mRNA水平的表达来研究钙通道的活性。
我们发现，连续4周给予100mg/kg/天的SAL不仅能降低血糖，还能降低糖尿病GK大鼠的血压，并减轻脑血管收缩活动，这表明SAL治疗可能同时为糖尿病患者提供降血糖和降血压的联合治疗。此外，SAL治疗显著抑制了从糖尿病GK大鼠分离的脑动脉血管平滑肌细胞（VSMCs）的功能和钙通道表达，或者在暴露于高血糖条件下时的功能和表达，这可能是SAL在糖尿病中发挥血管保护作用的潜在机制。
本研究提供了证据表明，SAL通过抑制平滑肌细胞中的钙通道，有助于降低糖尿病GK大鼠的血压并减轻脑血管收缩活动，这可能为治疗糖尿病患者的血管并发症提供一种新方法。
