Jiang Xiao-Wen, Zhang Bin-Qing, Qiao Lu, Liu Lin, Wang Xue-Wei, Yu Wen-Hui
Department of Veterinary Medicine, Northeast Agricultural University, Harbin, Helongjiang Province, China.
Neural Regen Res. 2018 Mar;13(3):484-491. doi: 10.4103/1673-5374.228732.
Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid (AKBA) is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1 day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index. Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore, for in vitro experiments, Schwann cells were treated with AKBA at 0-20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 (2.5 μL/mL), the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.
乳香可促进血液循环。乙酰-11-酮-β-乳香酸(AKBA)是一种具有抗炎特性的小分子,它源自锯叶乳香。在此,我们假设它可能促进受损坐骨神经的再生。为验证这一假设,我们采用神经夹伤法建立了大鼠坐骨神经损伤模型。从损伤后第1天起,大鼠每隔2天腹腔注射一次AKBA,剂量分别为1.5、3和6 mg/kg,持续30天。使用坐骨神经功能指数评估坐骨神经功能。使用腓肠肌Cuadros指数测量肌肉萎缩程度。通过苏木精-伊红染色观察神经病理学变化。采用蛋白质免疫印迹分析检测损伤神经中磷酸化细胞外信号调节激酶1和2(p-ERK1/2)的表达。通过免疫组织化学检测损伤神经中的S100免疫反应性。体内实验表明,3和6 mg/kg的AKBA显著提高了坐骨神经损伤模型大鼠受损坐骨神经的坐骨神经指数、腓肠肌Cuadros指数、p-ERK1/2表达和S100免疫反应性。此外,在体外实验中,雪旺细胞用0 - 20 μg/mL的AKBA处理。通过细胞计数试剂盒-8比色法检测雪旺细胞的增殖。结果表明,2 μg/mL的AKBA是最佳治疗浓度。此外,2 μg/mL AKBA处理后ERK磷酸化水平升高。在存在ERK1/2抑制剂PD98059(2.5 μL/mL)的情况下,AKBA诱导的p-ERK1/2蛋白表达增加被部分消除。总之,我们的研究表明AKBA促进周围神经再生,ERK蛋白磷酸化在此过程中起关键作用。