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Rep-PCR and Eric-PCR were used to evaluate the diversity of intestinal flora in feces of rats. RESULTS：Compared with normal
group，the writhing times of rats were increased significantly in model group；the contents of NO and MDA in uterus were
increased significantly，while the contents of acetic acid，propionic acid and butyric acid in colonic contents and total content of
SCFAs were decreased significantly （P＜0.05 or P＜0.01）；the number of DNA electrophoresis bands of intestinal flora was
significantly reduced，the brightness of most bands was significantly reduced，and the diversity indexes （by Rep-PCR and
Eric-PCR method，hereinafter）1 h after administration were significantly reduced（P＜0.05 or P＜0.01）. Compared with model
group，writhing times of rats were decreased significantly in capsule group，paeoniflorin group and paeonol group；the contents of
NO in uterus of rats in capsule group and paeoniflorin group as well as the contents of MDA in capsule group，paeoniflorin group
and paeonol group were decreased significantly（P＜0.05 or P＜0.01）；the propionic acid content and total content of SCFAs in
colon of rats in capsule group，the contents of acetic acid，propionic acid and butyric acid，total content of SCFAs in paeoniflorin
group as well as the contents of propionic acid and butyric acid，total content of SCFAs in paeonol group were increased
significantly；the content of isovaleric acid was decreased significantly in paeoniflorin group （P＜0.05 or P＜0.01）；DNA
electrophoresis bands and its brightness of intestinal flora changed to different extents in administration groups，and the diversity
indexes of intestinal flora 1 h after administration were increased significantly in capsule group and paeoniflorin group，while those
indexes were decreased significantly in paeonol group and amygdalin group（P＜0.05 or P＜0.01）. CONCLUSIONS：Guizhi fuling
capsules can significantly reduce writhing times and the contents of NO and MDA in uterus of primary dysmenorrhea model rats. At
the same time，the capsules also can regulate SCFAs content in colonic contents and intestinal flora diversity of rats. The above
effects may be related to paeoniflorin and paeonol in the capsules.
KEYWORDS Guizhi fuling capsules；Effective component；Primary dysmenorrhea；Short-chain fatty acids；Intestinal flora
diversity；Rat

桂枝茯苓胶囊是参照东汉张仲景《金匮要略》中的 此，本研究通过注射苯甲酸雌二醇和缩宫素建立大鼠原
经典名方桂枝茯苓丸经剂型改良而得，由桂枝、茯苓、桃 发性痛经模型 [13-14] ，在给予桂枝茯苓胶囊及其主要成分
仁、牡丹皮、芍药等5味中药组成，具有活血化瘀、消癥散 （芍药苷、丹皮酚、苦杏仁苷）的基础上，通过药效学指标
结等功效，临床主要用于妇人瘀血经络所致癥块、经闭、 来评价该药及其成分的治疗作用；同时，运用气相色谱
[1]
原发性痛经、产后恶露不尽等症 。研究表明，原发性痛 （GC）技术进一步考察大鼠结肠内容物中 SCFAs 的含
经与雌激素分泌密切相关，而雌激素紊乱可引起部分肠 量 ，借 助 细 菌 基 因 组 重 复 序 列 - 聚 合 酶 链 式 反 应
道菌群的显著改变 [2-3] 。肠道菌群种类繁多，是维持人体 （Rep-PCR）和肠杆菌基因组间重复序列-聚合酶链式反
正常消化功能的微生物，具有抵御感染和降低自身免疫 应（Eric-PCR）两种技术来分析大鼠肠道菌群多样性的
疾病发生风险的能力，其多样性直接反映了机体的健康 变化，以期阐明桂枝茯苓胶囊及主要成分对原发性痛经
状态 。短链脂肪酸（SCFAs）是由碳水化合物和蛋白质 模型大鼠肠道菌群的影响，为该药治疗原发性痛经的物
[4]
在厌氧环境下经肠道菌群发酵所生成的产物，主要包括 质基础和作用机制的深入研究提供参考。
乙酸、丙酸、异丁酸、丁酸、异戊酸、戊酸等，具有维持机 1 材料
体肠道微生态平衡的作用，是肠道菌群代谢的重要信息 1.1 仪器
分子，影响着体内雌激素、生长激素等激素的合成和分 Quant Studio 3型荧光定量PCR仪[赛默飞世尔科技
泌 [5-7] 。 （中国）有限公司]；PowerPac HC 型电泳系统、Universal
桂枝茯苓胶囊作为治疗原发性痛经的有效药物，其 HOOD Ⅱ型多功能凝胶成像仪[伯乐生命医学产品（上
主要成分芍药苷、丹皮酚、苦杏仁苷等具有抗氧化作用， 海）有限公司]；DNM-9602G 型酶标仪（北京普朗生物科
[8]
对痛经、卵巢囊肿等症的治疗均具有较好的效果 ；同 技有限公司）；Centrifuge 5424 型高速离心机（德国 Ep-
时，芍药苷可显著促进嗜酸乳杆菌和粪肠球菌的增殖 ， pendorf 公司）；7890B 型 GC 仪[安捷伦科技（中国）有限
[9]
丹皮酚、苦杏仁苷分别对两歧双歧杆菌、脆弱拟杆菌、 公司]；HH-4 型数显恒温水浴锅（常州国华电器有限公
丁酸梭菌以及金黄色葡萄球菌、大肠杆菌具有抑制作 司）；XS205DU型电子分析天平[梅特勒-托利多仪器（上
用 [10-11] 。由此可见，桂枝茯苓胶囊及其主要成分对大鼠 海）有限公司]；CT62A 型高压蒸汽灭菌锅（上海博讯实
病理状态下肠道菌群的调节具有重要意义。目前，关于 业有限公司医疗设备厂）；Milli-Q PACIFICT Ⅱ7型纯水
桂枝茯苓胶囊的研究主要集中于其各成分的含量测定 仪[密理博（上海）贸易有限公司）]。
以及药理活性、子宫评价指标以及子宫形态变化等方 1.2 药品与试剂
[12]
面 ，而关于该药对肠道菌群的影响尚未见报道。基于 桂枝茯苓胶囊（江苏康缘药业股份有限公司，批

中国药房 2020年第31卷第11期 China Pharmacy 2020 Vol. 31 No. 11 ·1321 ·