Conti Valeria, Randriamboavonjy Joseph Iharinjaka, Rafatro Herintsoa, Manzo Valentina, Dal Col Jessica, Filippelli Amelia, Corbi Graziamaria, Tesse Angela
Department of Medicine Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, S. Allende, 84081 Baronissi, SA, Italy.
Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d'Aragona University Hospital, San Leonardo 1, 84131 Salerno, SA, Italy.
Pharmaceuticals (Basel). 2023 May 18;16(5):761. doi: 10.3390/ph16050761.
Vascular aging is linked to reduce NO bioavailability, endothelial dysfunction, oxidative stress, and inflammation. We previously showed that a 4-week treatment of middle-aged Wistar rats (MAWRs, 46 weeks old) with seed powder (MOI, 750 mg/kg/day) improved vascular function. Here, we investigated the involvement of SIRT1 in MOI-induced vascular improvement. MAWRs were treated with a standard or MOI-containing diet. Young rats (YWR, 16 weeks old) were the controls and received a standard diet. The hearts and aortas were harvested to evaluate SIRT1 and FOXO1 expression via Western blot and/or immunostaining, SIRT1 activity via a fluorometric assay, and oxidative stress using the DHE fluorescent probe. In the hearts and aortas, SIRT1 expression, reduced in MAWRs compared to YWRs, was enhanced in MOI MAWRs. In the hearts, SIRT1 activity did not differ between YWRs and MAWRs, whereas it was increased in MOI MAWRs compared with them. In the aortas, SIRT1 activity decreased in MAWRs, and it was similar in the MOI MAWRs and YWRs. FOXO1 expression increased in the nuclei of MAWR aortas compared to YWR and was reversed in MOI MAWRs. Interestingly, MOI treatment normalized oxidative stress enhanced in MAWRs, in both the heart and aorta. These results demonstrate the protective role of MOI against cardiovascular dysfunction due to aging via enhanced SIRT1 function and subsequently reduced oxidative stress.
血管老化与一氧化氮生物利用度降低、内皮功能障碍、氧化应激和炎症有关。我们之前的研究表明，用种子粉（MOI，750毫克/千克/天）对中年Wistar大鼠（MAWRs，46周龄）进行4周治疗可改善血管功能。在此，我们研究了SIRT1在MOI诱导的血管改善中的作用。MAWRs接受标准饮食或含MOI的饮食。年轻大鼠（YWR，16周龄）作为对照，接受标准饮食。采集心脏和主动脉，通过蛋白质免疫印迹法和/或免疫染色评估SIRT1和FOXO1的表达，通过荧光测定法评估SIRT1活性，使用DHE荧光探针评估氧化应激。在心脏和主动脉中，与YWRs相比，MAWRs中降低的SIRT1表达在MOI处理的MAWRs中增强。在心脏中，YWRs和MAWRs之间的SIRT1活性没有差异，而与它们相比，MOI处理的MAWRs中的SIRT1活性增加。在主动脉中，MAWRs中的SIRT1活性降低，MOI处理的MAWRs和YWRs中的SIRT1活性相似。与YWRs相比，MAWRs主动脉细胞核中的FOXO1表达增加，而在MOI处理的MAWRs中则逆转。有趣的是，MOI处理使MAWRs心脏和主动脉中增强的氧化应激恢复正常。这些结果表明，MOI通过增强SIRT1功能并随后降低氧化应激，对衰老引起的心血管功能障碍具有保护作用。
