Xu Zhiming, Liu Yingliang, Yang Dianxu, Yuan Fang, Ding Jun, Chen Hao, Tian Hengli
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, NO. 600, Yi Shan Road, Xuhui District, Shanghai, 200030, China.
BMC Neurosci. 2017 Aug 7;18(1):57. doi: 10.1186/s12868-017-0378-8.
Sesamin is a well-known antioxidant extracted from sesame seeds that exhibits various curative effects. The present study investigated whether sesamin would protect neuroblastoma SH-SY5Y cells against mechanical stretch injury-induced increases in reactive oxygen species (ROS) and apoptosis. Additionally, the mechanisms underlying these actives were investigated. Following exposure to mechanical stretch injury, cells were incubated for further investigations. Lactate dehydrogenase and Cell Counting Kit-8 assays were used to assess cell viability, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometric analysis were performed to evaluate changes in mitochondrial membrane potential (ΔΨm). Furthermore, intracellular levels of ROS production were measured by 20, 70-dichlorofluorescein diacetate staining, the mRNA levels of matrix metallopeptidase 9 (MMP-9) were evaluated using real-time polymerase chain reaction analysis, and the determinations had also been made on related proteins by Western blot analysis.
Exposure to mechanical stretch injury significantly decreased cell viability but this decrease was attenuated by pretreatment with sesamin (50 μM). Sesamin also significantly inhibited mechanical stretch injury-induced increases in intracellular ROS production, attenuated declines in ΔΨm, diminished the expressions of pro-apoptotic proteins, and decreased cell apoptosis. Stretch injury increased Bax and cleaved caspase 3 levels, enhanced the gene expression of MMP-9, increased the phosphorylation levels of Akt, p38, and JNK and decreased Bcl-2 levels in the cells. However, pretreatment with sesamin reduced the mechanical stretch injury-induced overexpression of MMP-9.
Sesamin protected SH-SY5Y cells against stretch injury by attenuating increases in ROS levels and suppressing apoptosis. Accordingly, sesamin seems to be a potentially therapeutic agent in the treatment of traumatic brain injury.
芝麻素是一种从芝麻籽中提取的著名抗氧化剂，具有多种治疗作用。本研究调查了芝麻素是否能保护神经母细胞瘤SH-SY5Y细胞免受机械拉伸损伤诱导的活性氧（ROS）增加和细胞凋亡。此外，还研究了这些活性的潜在机制。在暴露于机械拉伸损伤后，将细胞孵育以进行进一步研究。使用乳酸脱氢酶和细胞计数试剂盒-8测定法评估细胞活力，并进行末端脱氧核苷酸转移酶dUTP缺口末端标记测定和流式细胞术分析以评估线粒体膜电位（ΔΨm）的变化。此外，通过2′,7′-二氯荧光素二乙酸酯染色测量细胞内ROS产生水平，使用实时聚合酶链反应分析评估基质金属肽酶9（MMP-9）的mRNA水平，并通过蛋白质印迹分析对相关蛋白质进行测定。
暴露于机械拉伸损伤显著降低细胞活力，但用芝麻素（50 μM）预处理可减轻这种降低。芝麻素还显著抑制机械拉伸损伤诱导的细胞内ROS产生增加，减轻ΔΨm的下降，减少促凋亡蛋白的表达，并降低细胞凋亡。拉伸损伤增加了细胞中Bax和裂解的半胱天冬酶3水平，增强了MMP-9的基因表达，增加了Akt、p38和JNK的磷酸化水平，并降低了Bcl-2水平。然而，用芝麻素预处理可降低机械拉伸损伤诱导的MMP-9过表达。
芝麻素通过减轻ROS水平升高和抑制细胞凋亡来保护SH-SY5Y细胞免受拉伸损伤。因此，芝麻素似乎是治疗创伤性脑损伤的一种潜在治疗剂。
