Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, People's Republic of China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People's Republic of China.
Drug Des Devel Ther. 2024 Jan 6;18:13-28. doi: 10.2147/DDDT.S421446. eCollection 2024.
This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD.
CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson's trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman's rank correlation coefficient were used for correlation analysis.
HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1β, TGF-β1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10.
Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.
本研究旨在探讨黄甘方（HGF），一种用于治疗慢性肾脏病（CKD）的中药方剂，对 CKD 肠道微生物群和结肠微环境的调节作用。
通过给予 150mg/kg 腺嘌呤灌胃 4 周，诱导 CKD 大鼠，然后用 3.6g/kg 或 7.2g/kg 的 HGF 进行 8 周的口服治疗。通过生化检测、苏木精和伊红、马松三色染色、天狼猩红和免疫化学染色分析肾功能和结构。记录平均粪便重量和结肠中的数量，以评估结肠蠕动。进一步通过 16S rRNA 测序、RT-PCR 或免疫荧光评估肠道微生物群和结肠微环境的变化。通过 RT-PCR、ELISA、氯胺-T 法或 Western blot 检测炎症细胞因子、尿毒症毒素和 NF-κB 信号通路的水平。采用冗余分析生物图和斯皮尔曼等级相关系数进行相关性分析。
HGF 显著改善了 CKD 的肾功能和病理损伤。HGF 可改善肠道微生物群失调，保护结肠屏障并促进结肠腔的蠕动。此外，HGF 通过降低 TNF-α、IL-6、IL-1β、TGF-β1 并抑制 NF-κB 信号通路，抑制全身炎症。HGF 治疗还降低了选定的尿毒症毒素的血清水平。Spearman 相关性分析表明，高剂量 HGF 抑制了与炎症因子（如 TNF-α）和尿毒症毒素（如吲哚硫酸酯）呈正相关的细菌过度生长，而促进了属于有益微生物群的细菌的增殖，并与 IL-10 水平呈正相关。
我们的结果表明，HGF 可以通过抑制全身炎症和尿毒症来改善腺嘌呤诱导的 CKD，这可能与肠道微生物群和结肠微环境的调节有关。
