清热解毒法抑制SIRT1有助于改善佐剂诱导的关节炎大鼠的免疫功能

Jian Zuo, Zhe Yang
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摘要

中药配方清-络-饮(QLY)被证实含有 SIRT1 抑制剂。它们是否有助于抗风湿作用还有待证实。用 QLY 或/和烟酰胺单核苷酸(NMN)治疗佐剂诱导的关节炎(AIA)大鼠 38 天。牺牲后,收集主要组织进行组织学和西方印迹实验。血液或组织匀浆中类风湿性关节炎(RA)相关指标的水平由商用试剂盒检测。用相关的大鼠血清培养正常的前脂肪细胞,并收集培养基用于单核细胞培养。在重复实验中,一些前脂肪细胞接受了额外的化合物或 SIRT1 沉默/外显处理。由于炎症的自发缓解,QLY 没有进一步改善 AIA 大鼠的免疫环境,但大大缓解了爪水肿和关节损伤。此外,它还逆转了肝脏和脂肪组织中甘油三酯/葡萄糖的耗竭,抑制了 SIRT1 的表达和功能,导致相关信号和脂肪因子的产生发生同步变化。NMN 可通过增加 NAD 的产生来激活 SIRT1。马钱子碱、西诺明碱、苏佛卡平碱、地奥司辛、小檗碱的混合物对前脂肪细胞的影响与含 QLY 的血清相似。QLY 中的 SIRT1 抑制剂重塑了脂肪组织的新陈代谢和分泌曲线。因此,它减轻了 eNAMPT 介导的炎症,缓解了大鼠的 AIA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Qing-Luo-Yin-induced SIRT1 inhibition contributes to the immune improvement of adjuvant-induced arthritis rats
The herbal formula Qing-Luo-Yin (QLY) was proved containing SIRT1 inhibitors. Whether they contribute to the anti-rheumatic effects is to be confirmed. Adjuvant-induced arthritis (AIA) rats were treated by QLY or/and nicotinamide mononucleotide (NMN) for 38 days. After sacrifice, main tissues were collected for histological and western-blot experiments. Levels of rheumatoid arthritis (RA)-related indictors in blood or tissue homogenates were detected by commercial kits. Normal pre-adipocytes were cultured by the relevant rat serums, and the medium was collected for monocytes culture. In replicate experiments, some pre-adipocytes received additional compounds or SIRT1 silencing/overexpression treatments. Due to spontaneous remission of inflammation, QLY did not further improve immune milieu in AIA rats, but greatly eased paw edema and joint injuries. Besides, it reversed triglyceride/glucose depletion in liver and adipose tissues, and inhibited the expression and function of SIRT1, causing concomitant changes of related signals and adipkines production. All the effects were weakened by NMN, which activated SIRT1 by increasing NAD production. in the monocytes cultured with the corresponding medium. A mixture of matrine, sinomenine, sophocarpine, dioscin, berberine showed the similar effects on pre-adipocytes to QLY-containing serum. eNAMPT decrease was especially notable, which was obviously weakened by SIRT1 overexpression but overshadowed SIRT1-silencing. SIRT1 inhibitors in QLY reshaped metabolism and secretion profiles of adipose tissues. It consequently mitigated eNAMPT-mediated inflammation and eased AIA in rats.
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