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补气通窍方对免疫球蛋白A肾病大鼠肠道菌群及免疫平衡的调节作用研究
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| 篇名： | 补气通窍方对免疫球蛋白A肾病大鼠肠道菌群及免疫平衡的调节作用研究 |
| TITLE： | Study on the regulatory effects of Buqi tongqiao formula on intestinal flora and immune balance in IgA nephropathy rats |
| 摘要： | 目的 基于“异病同治”理论探讨补气通窍方对免疫球蛋白A肾病（IgAN）大鼠肠道菌群及免疫平衡的调节作用。方法将雄性SD大鼠随机分为空白组（Normal组）和造模组。造模组大鼠以灌胃牛血清白蛋白+皮下注射四氯化碳和蓖麻油混合液+尾静脉注射脂多糖的方式构建IgAN大鼠模型。将造模成功的大鼠随机分为模型组（Model组）、补气通窍方低剂量组（BQTQ-L组）、补气通窍方高剂量组（BQTQ-H组）、阳性对照组（BZP组），每组15只。BZP组灌胃盐酸贝那普利10mg/kg，BQTQ-L组、BQTQ-H组大鼠分别灌胃补气通窍方9.81、19.62g/kg（以生药量计），Normal组和Model组大鼠灌胃等体积生理盐水，每天1次，连续8周。分别于实验第8、10、12、14、16周检测各组大鼠的24h尿蛋白（24hUTP）含量；于末次给药后检测其血清肌酐（Scr）和血尿素氮（BUN）含量，观察其肾组织病理改变和肾小球IgA免疫复合物沉积情况；分析各组小鼠的肠道菌群变化情况和外周血辅助性T细胞17（Th17）、调节性T细胞（Treg）比例和二者比值（Th17/Treg）。结果与Model组相比，BQTQ-L组、BQTQ-H组大鼠肾小球系膜细胞增生和基质增生均有所减轻，炎症细胞浸润减少；其24hUTP含量（BQTQ-L组第14、16周，BQTQ-H组第12、14、16周），Scr、BUN含量，IgA阳性区域荧光强度，厚壁菌门的相对丰度，Th17比例，Th17/Treg均显著降低（P＜0.05）；Chao1指数、Observedspe‐cies指数、Shannon指数、Simpson指数（BQTQ-H组除外），拟杆菌门的相对丰度和Treg比例均显著升高（P＜0.05）；差异微生物包括c_Clostridia（BQTQ-L组vs.Model组）、g_Ruminococcus（BQTQ-H组vs.Model组）等。结论补气通窍方可能通过调控肠道菌群稳态和Th17/Treg免疫平衡来缓解IgAN大鼠肾损伤，发挥肾脏保护作用。 |
| ABSTRACT： | OBJECTIVE To explore the regulatory effects of Buqi tongqiao formula on intestinal flora and immune balance in immunoglobulin A nephropathy （IgAN） rats based on the theory of “treating different diseases with the same therapy”. METHODS Male SD rats were randomly assigned to the Normal group and the modeling group. IgAN rat models were established in the modeling group by intragastric administration of bovine serum albumin， subcutaneous injection of carbon tetrachloride and castor oil mixture， and tail vein injection of lipopolysaccharide. Successfully modeled rats were then randomly divided into the model group （Model group）， Buqi tongqiao formula low-dose group （BQTQ-L group）， Buqi tongqiao formula high-dose group （BQTQ- H group）， and positive control group （BZP group）， with 15 rats in each group. BZP group received intragastric administration of benazepril hydrochloride （10 mg/kg）， while BQTQ-L and BQTQ-H groups were given Buqi tongqiao formula at doses of 9.81 and 19.62 g/kg （calculated as raw herb weight）， respectively. The Normal group and the Model group received an equal volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The 24-hour urinary total protein （24 h UTP） contents were measured at weeks 8， 10， 12， 14 and 16 of the experiment. After the last administration， serum creatinine （Scr） and blood urea nitrogen （BUN） contents were detected. Renal histopathological changes and glomerular IgA immune complex deposition were examined. Additionally， alterations in gut microbiota composition， the proportions of peripheral T helper cell 17 （Th17） and regulatory T cell （Treg）， as well as the ratio of Th17 and Treg （Th17/Treg）， were analyzed across all groups. RESULTS Compared with the Model group， rats in both BQTQ-L and BQTQ-H groups showed alleviated mesangial cell hyperplasia， reduced matrix expansion， and decreased IgA immune complex deposition in the glomeruli. The 24 h UTP contents （at weeks 14 and 16 in the BQTQ-L group； at weeks 12， 14 and 16 in the BQTQ-H group）， Scr and BUN contents， IgA-positive area fluorescence intensities， relative abundances of Firmicutes， Th17 cell proportions， and Th17/Treg were significantly decreased in both BQTQ-L and BQTQ-H groups （P＜0.05）； while the Chao1， Observed species， Shannon， and Simpson （except for BQTQ-H group） indexes， the relative abundances of Bacteroidota， and the proportions of Treg were significantly increased （P＜0.05）. Differential microbiota included c_Clostridia （BQTQ-L group vs. Model group） and g_Ruminococcus （BQTQ-H group vs. Model group）， etc. CONCLUSIONS Buqi tongqiao formula may alleviate renal injury and exert a renal protective effect in IgAN rats by modulating intestinal flora homeostasis and Th17/Treg immune balance. |
| 期刊： | 2025年第36卷第20期 |
| 作者： | 徐锦江；张曼；吴秋烨；桂雄斌 |
| AUTHORS： | XU Jinjiang，ZHANG Man，WU Qiuye，GUI Xiongbin |
| 关键字： | 补气通窍方；免疫球蛋白A肾病；肠道菌群；免疫平衡；异病同治 |
| KEYWORDS： | Buqi tongqiao formula； immunoglobulin A nephropathy； intestinal flora； immune balance； treating different |
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