Chen Peng, Wang Chen, Luo Rui-Xi, Wu Zhi-Bing, Xia Dong-Bin
Basic Medical School, Guizhou University of Traditional Chinese Medicine Guiyang 550025, China.
Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University Guangzhou 510280, China.
Zhongguo Zhong Yao Za Zhi. 2022 Apr;47(8):2187-2194. doi: 10.19540/j.cnki.cjcmm.20211027.402.
The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery. Mechanical withdrawal threshold(MWT) and thermal withdrawal threshold(TWL) in each group were performed before the CCI surgery and 3,7, 11, and 15 days after surgery. After 15 days, blood samples were collected from the abdominal aorta. The differential metabolites were screened out by non-target metabolomics and analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG) and ingenuity pathway analysis(IPA). From the third day after CCI surgery, the MWT and TWL values were reduced significantly in both CCI group and emodin group, compared with the sham group(P<0.01). At 15 days post-surgery, the MWT and TWL values in emodin group increased significantly compared with the CCI group(P<0.05). As revealed by non-target metabolomics, 72 differential serum metabolites were screened out from the C-S comparison, including 41 up-regulated and 31 down-regulated ones, while 26 differential serum metabolites from E-C comparison, including 10 up-regulated and 16 down-regulated ones. KEGG analysis showed that the differential metabolites in E-C comparison were enriched in the signaling pathways, such as sphingolipid metabolism, arginine biosynthesis, glycerophospholipid metabolism, and tryptophan metabolism. IPA showed that the differential metabolites were mainly involved in the lipid metabolism-molecular transport-small molecule biochemistry network. In conclusion, emodin can exert an analgesic role via regulating sphingolipid metabolism and arginine biosynthesis.
本研究通过非靶向代谢组学研究了大黄素对慢性缩窄性损伤（CCI）模型血清代谢物谱的影响，并探讨其镇痛机制。将24只Sprague Dawley（SD）大鼠随机分为假手术组（S）、CCI组（C）和大黄素组（E）。大黄素组大鼠在CCI手术后第1天开始每天经口灌胃给予大黄素一次，持续15天（50 mg·kg⁻¹）。在CCI手术前以及手术后3、7、11和15天测定每组大鼠的机械缩足阈值（MWT）和热缩足阈值（TWL）。15天后，从腹主动脉采集血样。通过非靶向代谢组学筛选差异代谢物，并利用京都基因与基因组百科全书（KEGG）和 Ingenuity 通路分析（IPA）进行分析。与假手术组相比，CCI手术后第3天起，CCI组和大黄素组的MWT和TWL值均显著降低（P<0.01）。术后15天，大黄素组的MWT和TWL值与CCI组相比显著升高（P<0.05）。非靶向代谢组学结果显示，C-S比较筛选出72种差异血清代谢物，其中上调41种，下调31种；E-C比较筛选出26种差异血清代谢物，其中上调10种，下调16种。KEGG分析表明，E-C比较中的差异代谢物在鞘脂代谢、精氨酸生物合成、甘油磷脂代谢和色氨酸代谢等信号通路中富集。IPA显示，差异代谢物主要参与脂质代谢-分子转运-小分子生物化学网络。综上所述，大黄素可通过调节鞘脂代谢和精氨酸生物合成发挥镇痛作用。
