Hsu Mei-Hsin, Huang Yi-Chuan, Chen Yu-Chieh, Sheen Jiunn-Ming, Huang Li-Tung
Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 833, Taiwan.
Chiayi Chang Gung Memorial Hospital, Puzi City 613, Taiwan.
Pharmaceuticals (Basel). 2023 May 31;16(6):825. doi: 10.3390/ph16060825.
Endothelial dysfunction is characterized by disturbances in nitric oxide (NO) bioavailability and increased circulating asymmetric dimethylarginine (ADMA) due to the enormous release of free radicals. Increased circulating ADMA may cause endothelial dysfunction and a variety of clinical disorders, such as liver and kidney disease. Young male Sprague-Dawley rats at postnatal day 17 ± 1 received continuous ADMA infusion via an intraperitoneal pump to induce endothelial dysfunction. Four groups of rats ( = 10 per group) were allocated: control, control and resveratrol, ADMA infusion, and ADMA infusion and resveratrol groups. Spatial memory, NLR family pyrin-domain-containing 3 (NLRP3) inflammasome, cytokine expression, tight junction proteins in the ileum and dorsal hippocampus, and microbiota composition were examined. We found cognitive deficits; increased NLRP3 inflammasome in the plasma, ileum, and dorsal hippocampus; decreased ileum and dorsal hippocampal cytokine activation and tight junction proteins; and microbiota composition alterations in the ADMA-infusion young male rats. Resveratrol had beneficial effects in this context. In conclusion, we observed NLRP3 inflammasome activation in peripheral and central dysbiosis in young male rats with increased circulating ADMA, and found that resveratrol had beneficial effects. Our work adds to the mounting evidence that inhibiting systemic inflammation is a promising therapeutic avenue for cognition impairment, probably via the gut-brain axis.
内皮功能障碍的特征是一氧化氮（NO）生物利用度紊乱，以及由于自由基大量释放导致循环中不对称二甲基精氨酸（ADMA）增加。循环中ADMA增加可能导致内皮功能障碍和多种临床疾病，如肝脏和肾脏疾病。出生后17±1天的年轻雄性Sprague-Dawley大鼠通过腹腔内泵持续输注ADMA以诱导内皮功能障碍。将四组大鼠（每组n = 10）进行分配：对照组、对照组加白藜芦醇组、ADMA输注组以及ADMA输注加白藜芦醇组。检测了空间记忆、含NLR家族吡啶结构域3（NLRP3）炎性小体、细胞因子表达、回肠和背侧海马体中的紧密连接蛋白以及微生物群组成。我们发现ADMA输注的年轻雄性大鼠存在认知缺陷；血浆、回肠和背侧海马体中NLRP3炎性小体增加；回肠和背侧海马体细胞因子激活和紧密连接蛋白减少；以及微生物群组成改变。在这种情况下，白藜芦醇具有有益作用。总之，我们观察到循环ADMA增加的年轻雄性大鼠外周和中枢生态失调中NLRP3炎性小体激活，并发现白藜芦醇具有有益作用。我们的工作进一步证明，抑制全身炎症可能是治疗认知障碍的一条有前景的途径，可能是通过肠-脑轴实现的。
