Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Molecules. 2012 Sep 20;17(9):11216-28. doi: 10.3390/molecules170911216.
Salvianolic acid A (SalA) is one of the main efficacious, water-soluble constituents of Salvia miltiorrhiza Bunge. This study investigated the protective effects of SalA on peripheral nerve in diabetic rats. Administration of SalA (0.3, 1 and 3 mg/kg, ig) was started from the 5th week after strepotozotocin (STZ60 mg/kg) intraperitoneal injection and continued for 8 weeks. Paw withdrawal mechanical threshold (PWMT) and motor nerve conduction velocity (MNCV) were used to assess peripheral nerve function. The western blot methods were employed to test the expression levels of serine-threonine liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), silent information regulator protein3 (sirtuin 3/Sirt3) and neuronal nitric oxide synthase (nNOS) in sciatic nerve. Results showed that SalA administration could increase PWMT and MNCV in diabetic rats; reduce the deterioration of sciatic nerve pathology; increase AMPK phosphorylation level, up-regulate PGC-1α, Sirt3 and nNOS expression, but had no influence on LKB1. These results suggest that SalA has protective effects against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve function in diabetic rats might be attributed to improvements in glucose metabolism through regulation of the AMPK-PGC1α-Sirt3 axis.
丹酚酸 A（SalA）是丹参中主要的水溶性有效成分之一。本研究旨在探讨丹酚酸 A 对糖尿病大鼠周围神经的保护作用。自链脲佐菌素（STZ60mg/kg）腹腔注射后第 5 周开始给予 SalA（0.3、1 和 3mg/kg，ig）治疗，持续 8 周。采用足底机械刺激阈值（PWMT）和运动神经传导速度（MNCV）评估周围神经功能。采用 Western blot 方法检测坐骨神经中丝氨酸-苏氨酸激酶 B1（LKB1）、AMP 激活的蛋白激酶（AMPK）、过氧化物酶体增殖物激活受体-γ共激活因子 1α（PGC-1α）、沉默信息调节蛋白 3（Sirtuin 3/Sirt3）和神经元型一氧化氮合酶（nNOS）的表达水平。结果表明，SalA 可增加糖尿病大鼠的 PWMT 和 MNCV；减轻坐骨神经病理恶化；增加 AMPK 磷酸化水平，上调 PGC-1α、Sirt3 和 nNOS 的表达，但对 LKB1 无影响。这些结果表明，SalA 对糖尿病神经病变具有保护作用。SalA 改善糖尿病大鼠周围神经功能的有益作用可能归因于通过调节 AMPK-PGC1α-Sirt3 轴改善葡萄糖代谢。
