Feng Yu, Huang Zhihai, Ma Xiaohui, Zong Xuemei, Tesic Vesna, Ding Baojin, Wu Celeste Yin-Chieh, Lee Reggie Hui-Chao, Zhang Quanguang
Institute for Cerebrovascular and Neuroregeneration Research, Shreveport, LA 71103, USA.
Department of Neurology, Louisiana State University Health, Shreveport, LA 71103, USA.
Antioxidants (Basel). 2024 May 23;13(6):633. doi: 10.3390/antiox13060633.
Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment. Both rat photothrombotic (PT) stroke and in vitro oxygen-glucose deprivation (OGD)-induced vascular endothelial injury models were utilized. We demonstrated that treatment with PBMT (808 nm, 350 mW/cm, 2 min/day) for 7 days significantly reduced PT-stroke-induced vascular permeability. Additionally, PBMT inhibited the levels of endothelial senescence markers (senescence green and p21) and antiangiogenic factor (endostatin), while increasing the phospho-eNOS (Ser1177) in the peri-infarct region following PT stroke. In vitro study further indicated that OGD increased p21, endostatin, and DNA damage (γH2AX) levels in the brain endothelial cell line, but they were reversed by PBMT. Intriguingly, the beneficial effects of PBMT were attenuated by a NOS inhibitor. In summary, these findings provide novel insights into the role of eNOS in PBMT-mediated protection against cerebrovascular senescence and endothelial dysfunction following ischemia. The use of PBMT as a therapeutic is a promising strategy to improve endothelial function in cerebrovascular disease.
近期研究表明，光生物调节疗法（PBMT）对与各种脑血管疾病相关的血管功能有积极影响。然而，PBMT改善血管功能的具体机制仍不明确。由于内皮型一氧化氮合酶（eNOS）在脑缺血后调节血管功能中起关键作用，我们研究了eNOS是否是控制PBMT治疗后脑血管功能和血管内皮细胞衰老的关键因素。我们使用了大鼠光血栓形成（PT）性中风模型和体外氧糖剥夺（OGD）诱导的血管内皮损伤模型。我们证明，用PBMT（808纳米，350毫瓦/平方厘米，每天2分钟）治疗7天可显著降低PT性中风诱导的血管通透性。此外，PBMT抑制了梗死周边区域内皮衰老标志物（衰老绿色荧光和p21）和抗血管生成因子（内皮抑素）的水平，同时增加了PT性中风后梗死周边区域的磷酸化eNOS（Ser1177）水平。体外研究进一步表明，OGD增加了脑内皮细胞系中p21、内皮抑素和DNA损伤（γH2AX）水平，但PBMT可使其逆转。有趣的是，PBMT的有益作用被一氧化氮合酶抑制剂减弱。总之，这些发现为eNOS在PBMT介导的缺血后预防脑血管衰老和内皮功能障碍中的作用提供了新的见解。使用PBMT作为一种治疗方法是改善脑血管疾病中内皮功能的一种有前景的策略。
