Di Jiaxin, Guo Meifang, Peng Maijiao, Fang Leyao, Shen Junxi, Xiao Nenqun, Tan Zhoujin
School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People's Republic of China.
J Inflamm Res. 2025 Aug 4;18:10467-10487. doi: 10.2147/JIR.S518370. eCollection 2025.
To investigate the therapeutic mechanisms of sodium butyrate combined with SSP in treating diarrhea with kidney-yang deficiency syndrome, providing experimental evidence for the modern application of classical Chinese medicine formulas.
A mouse model of diarrhea with kidney-yang deficiency syndrome was established via adenine combined with gavage. After successful model establishment, the drug intervention groups were administered by gavage with 100% SSP decoction, 300 mg/mL sodium butyrate, and 100 mg/kg sodium butyrate + 50% SSP decoction, respectively. General physical conditions and organ indices were assessed. Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, as well as colonic immunoglobulin A (sIgA) and mucin 2 (MUC2) levels, were determined via ELISA. Kidney and intestinal histology were evaluated via hematoxylin‒eosin (HE) staining. The characteristics of the small intestinal mucosal microbiota under different interventions were analysed via 16S rRNA sequencing.
Compared with natural recovery, the combination of 100 mg/kg sodium butyrate + 50% SSP significantly restored colonic sIgA levels (< 0.05) and MUC2 levels, indicating an improvement in intestinal mucosal barrier function. Histological analysis revealed that the combination of 100 mg/kg sodium butyrate + 50% SSP improved renal inflammation and restored intestinal villus length and crypt depth. The combination therapy controlled the relative abundance of while restoring and . Correlation analysis indicated that and were significantly negatively correlated with sIgA and MUC2 levels and that their relative abundances were inhibited by the combination therapy.
Sodium butyrate enhanced the therapeutic efficacy of SSP. The combination therapy effectively repaired damaged kidneys and intestines and alleviated diarrhea with kidney-Yang deficiency syndrome by modulating the relative abundance of intestinal microbiota and enhancing intestinal immunity as well as mucosal barrier function. The interaction between the intestinal microbiota and intestinal mucosal protective factors may be a key mechanism in the combined treatment of diarrhea with kidney-yang deficiency syndrome.
探讨丁酸钠联合四神丸治疗肾阳虚泄泻证的作用机制，为经典中药方剂的现代应用提供实验依据。
采用腺嘌呤联合灌胃法建立肾阳虚泄泻证小鼠模型。造模成功后，药物干预组分别灌胃给予100%四神丸水煎液、300 mg/mL丁酸钠、100 mg/kg丁酸钠+50%四神丸水煎液。评估一般身体状况和脏器指数。通过酶联免疫吸附测定法（ELISA）检测血清肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平，以及结肠免疫球蛋白A（sIgA）和黏蛋白2（MUC2）水平。通过苏木精-伊红（HE）染色评估肾脏和肠道组织学。通过16S rRNA测序分析不同干预下小肠黏膜微生物群的特征。
与自然恢复组相比，100 mg/kg丁酸钠+50%四神丸联合使用显著恢复了结肠sIgA水平（<0.05）和MUC2水平，表明肠道黏膜屏障功能得到改善。组织学分析显示，100 mg/kg丁酸钠+50%四神丸联合使用改善了肾脏炎症，恢复了肠绒毛长度和隐窝深度。联合治疗在恢复[具体指标1]和[具体指标2]的同时，控制了[相关微生物]相对丰度。相关性分析表明，[相关微生物1]和[相关微生物2]与sIgA和MUC2水平显著负相关，联合治疗抑制了它们的相对丰度。
丁酸钠增强了四神丸的治疗效果。联合治疗通过调节肠道微生物群的相对丰度、增强肠道免疫力以及黏膜屏障功能，有效修复了受损的肾脏和肠道，缓解了肾阳虚泄泻证。肠道微生物群与肠道黏膜保护因子之间的相互作用可能是联合治疗肾阳虚泄泻证的关键机制。
