护卵汤加减方对多囊卵巢综合征模型大鼠肠道菌群的影响*

作者：杨永琴，魏本君，申 剑，王帅哲，马睿玲，胡 杨，杨 燕

单位：甘肃中医药大学，甘肃 兰州 730000

引用：引用：杨永琴，魏本君，申剑，王帅哲，马睿玲，胡杨，杨燕.护卵汤加减方对多囊卵巢综合征模型大鼠肠道菌群的影响[J].中医药导报,2026,32(1):48-56,86.

DOI：10.13862/j.cn43-1446/r.2026.01.008

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摘要：

目的：分析护卵汤加减方对多囊卵巢综合征（PCOS）模型大鼠肠道菌群的影响及其可能机制。方法：62只SD大鼠随机取8只为空白组，余54只每日予来曲唑灌胃诱导建立PCOS模型。将造模成功的54只大鼠分为模型组、西药组和中药组，每组18只。空白组及模型组给予0.9%NaCl注射液2 mL灌胃，西药组给予达英-35（0.339 2 mg/kg）灌胃，中药组给予护卵汤2 mL（含生药1.937 5 g/mL）灌胃，各组均连续治疗21 d。采集大鼠结肠内粪便进行16S rDNA检测，分析样本菌群的多样性与丰度，探讨其门、纲、属、种、科水平的物种组成。结果：与空白组比较，模型组大鼠空腹血糖升高（P＜0.05）；与模型组比较，中药组和西药组大鼠空腹血糖均降低（P＜0.05）；与西药组比较，中药组大鼠空腹血糖降低（P＜0.05）；与空白组比较，模型组大鼠卵巢湿质量、子宫湿质量、肝脏指数显著升高（P＜0.01）；与模型组比较，中药组大鼠卵巢湿质量、子宫湿质量显著降低（P＜0.01）；与空白组比较，模型组大鼠胆固醇酯（CHO）、甘油三酸酯（TG）和低密度脂蛋白（LDL）水平均上升，高密度脂蛋白（HDL）下降（P＜0.01）；与模型组比较，中药组TG、CHO和LDL均降低、HDL水平升高（P＜0.01）；与西药组比较，中药组在升高HDL上更具优势（P＜0.05）；与空白组比较，模型组大鼠血清激素所有指标差异均有统计学意义（P＜0.01）；与模型组比较，中药组大鼠血清FSH和E2含量上升（P＜0.01），LH、AMH、T及INS含量显著降低（P＜0.01）；与空白组比较，模型组大鼠可见卵巢中多个囊性扩张卵泡，卵泡颗粒层可见明显变薄，间质明显增生，卵母细胞未见；与模型组比较，中药组大鼠卵巢形态改变可见部分恢复，颗粒细胞层数增多，出现卵母细胞，囊性卵泡减少。空白组、模型组、中药组与西药组大鼠菌群ɑ多样性水平差异均无统计学意义（P＞0.05），肠道菌群β多样性的主坐标分析（PCoA）结果显示，PCoA 1和PCoA 2轴的累计解释度为54.3%（PCoA 1：32.5%；PCoA 2：21.8%），能够较好地反映各组间菌群结构的差异特征。中药组与模型组的显著分离，证实了药物的菌群调控效果。与空白组比较，模型组弯曲菌属差异有统计学意义（P＜0.05）。与模型组比较，中药组在门、纲、属、种、科水平的菌种差异有统计学意义（P＜0.05）。结论：护卵汤加减方对PCOS模型大鼠肠道菌群多样性改变有明显的调节作用，并且其作用机制与调节特定菌群有关。

关键词：多囊卵巢综合征；护卵汤加减方；颗粒细胞；细胞凋亡；PI3K/Akt信号通路；16S rDNA；大鼠

Abstract：

Objective: To analyze the effects of the modified Huluan decoction on the gut microbiota and its possible mechanisms in rat model of polycystic ovary syndrome (PCOS). Methods: Totally 62 SD rats were randomly assigned, with 8 in the blank group. The remaining 54 rats were administered letrozole daily via gavage to induce PCOS. The 54 successfully modeled rats were subsequently divided into the model group, Western medicine group, and traditional Chinese medicine (TCM) group, with 18 rats in each. The blank and model groups received 2 mL of 0.9% NaCl solution via gavage. The Western medicine group received Diane-35 (0.339 2 mg/kg), and the TCM group received 2 mL of modified Huluan decoction (containing 1.937 5 g/mL of crude drug) via gavage for 21 consecutive days. Fecal samples from the rat colon were collected for 16S rDNA sequencing to analyze the diversity and abundance of the microbial community and to investigate the species composition at the phylum, class, family, genus, and species levels. Results: The model group showed higher fasting blood glucose than blank group (P<0.05). Compared with the model group, both the TCM group and Western medicine group showed decreased fasting blood glucose (P<0.05). Furthermore, the TCM group showed lower fasting blood glucose than the Western medicine group (P<0.05). Compared with the blank group, ovarian wet weight, uterine wet weight, and liver index were significantly increased in the model group (P<0.01). Compared with the model group, ovarian and uterine wet weights were significantly decreased in the TCM group (P<0.01). Compared with the blank group, cholesterol (CHO), triglycerides (TG), and low-density lipoprotein (LDL) levels increased, while high-density lipoprotein (HDL) decreased in the model group (P<0.01). Compared with the model group, the TCM group showed decreased TG, CHO, and LDL, while increased HDL levels (P<0.01). The TCM group was superior to the Western medicine group in increasing HDL (P<0.05). All serum hormone levels differed significantly between the model and blank groups (P<0.01). Compared with the model group, the TCM group showed increased FSH and E2 (P<0.01), and significantly decreased LH, AMH, T, and INS (P<0.01). Compared with the blank group, the model group rats showed multiple cystically dilated follicles in the ovaries, markedly thinned granulosa cell layers, significant stromal hyperplasia, and no oocytes were observed. Compared with the model group, the TCM group exhibited partial restoration of ovarian morphology, increased layers of granulosa cells, presence of oocytes, and a reduction in cystic follicles. No significant difference in α-diversity was found among the blank group, model group, Western medicine group, and TCM group (P>0.05). Principal coordinate analysis (PCoA) of gut microbiota β-diversity showed that the cumulative explanation of PCoA1 and PCoA2 axes was 54.3% (PCoA1: 32.5%; PCoA2: 21.8%), which could effectively reflect the structural differences in microbiota among the groups. The significant separation between the TCM group and the model group confirmed the regulatory effect of the drug on the microbiota. Compared with the blank group, the model group showed a statistically significant difference in the genus Campylobacter (P<0.05). Compared with the model group, the TCM group showed statistically significant differences in bacterial species at the phylum, class, genus, species, and family levels (P<0.05). Conclusion: The modified Huluan decoction can significantly modulate gut microbiota diversity in PCOS model rats, and its mechanism is related to regulating specific microbial communities.

Key words：polycystic ovary syndrome; modified Huluan decoction; granulosa cells; apoptosis; PI3K/Akt signaling pathway; 16S rDNA; rat

发布时间：2026-01-30

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