Effect of <italic style="font-style: italic">Huoxue Jiedu Formula </italic>（活血解毒方） on Intestinal Flora in NOD Mice

Haiyu WANG; Yuting ZHANG; Zhiyi BAI; Yuan LI; Ruoyi WANG; Yongfeng WANG; Xiaoping LIU; Yuelan ZHU; Xiujuan HOU

doi:10.13288/j.11-2166/r.2022.01.011

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Effect of Huoxue Jiedu Formula （活血解毒方） on Intestinal Flora in NOD Mice

更新时间：2021-12-27

- Effect of Huoxue Jiedu Formula （活血解毒方） on Intestinal Flora in NOD Mice
- Journal of Traditional Chinese Medicine Vol. 63, Issue 1, Pages: 56-63(2022)
- 作者机构：
  
  1.北京中医药大学，北京市朝阳区北三环东路11号，100029
  2.北京中医药大学东方医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.01.011
  CLC：
- Received：27 May 2021，
  
  Revised：2021-09-01，
  
  Published：02 January 2022
- 稿件说明：
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王海瑜,张玉婷,柏志义等.活血解毒方对NOD小鼠肠道菌群的影响[J].中医杂志,2022,63(01):56-63.

WANG Haiyu,ZHANG Yuting,BAI Zhiyi,et al.Effect of Huoxue Jiedu Formula （活血解毒方） on Intestinal Flora in NOD Mice[J].Journal of Traditional Chinese Medicine,2022,63(01):56-63.
王海瑜,张玉婷,柏志义等.活血解毒方对NOD小鼠肠道菌群的影响[J].中医杂志,2022,63(01):56-63. DOI： 10.13288/j.11-2166/r.2022.01.011.

WANG Haiyu,ZHANG Yuting,BAI Zhiyi,et al.Effect of Huoxue Jiedu Formula （活血解毒方） on Intestinal Flora in NOD Mice[J].Journal of Traditional Chinese Medicine,2022,63(01):56-63. DOI： 10.13288/j.11-2166/r.2022.01.011.

摘要

目的

探讨活血解毒方治疗干燥综合征的可能作用机制。

方法

35只干燥综合征经典动物模型NOD小鼠随机分为模型组、白芍总苷组及活血解毒方高、中、低剂量组，每组７只，另设7只C57BL/6J小鼠作为正常组。正常组与模型组小鼠均以10 ml/kg蒸馏水灌胃，白芍总苷组以234 mg/kg白芍总苷胶囊灌胃，活血解毒方高、中、低剂量组分别按62.4、31.2、15.6 g/（kg·d）灌胃活血解毒方。8周后观察各组小鼠颌下腺病理染色结果并进行评分，同时通过高通量测序检测各组小鼠肠道菌群的组成结构、优势菌群，并进行多样性分析。

结果

与正常组比较，模型组、白芍总苷组颌下腺病理组织评分升高（

＜0.01）。HE染色显示，模型组可见外分泌腺结构破坏，腺泡不同程度萎缩，组织出现多灶性淋巴细胞浸润；活血解毒方各剂量组上述病理损伤减轻，少量散在淋巴细胞浸润，但未聚集成灶，其中活血解毒方中、高剂量组淋巴细胞浸润程度较活血解毒方低剂量组减轻。基于门水平分析，与正常组比较，模型组疣微菌门丰度降低、TM7菌门丰度升高（

＜0.05）；与模型组及白芍总苷组比较，活血解毒方低剂量组脱铁杆菌门丰度均升高（

＜0.05）。基于属水平分析，与正常组比较，模型组臭味杆菌属丰度升高、普氏菌属丰度降低（

＜0.05或

＜0.01）；与活血解毒方低剂量组比较，活血解毒方高剂量组臭味杆菌属丰度降低（

＜0.01）。组间差异菌种筛选结果显示，正常组优势菌种19种，模型组优势菌种6种，白芍总苷组优势菌群1种，活血解毒方低、中、高剂量组优势菌种分别为6种、2种、8种。Alpha多样性分析显示，与正常组比较，模型组Faith_Pd指数下降（

＜0.05）；与模型组比较，活血解毒方低、中剂量组Faith_Pd指数均升高（

＜0.01）。Beta多样性分析显示，除活血解毒方低剂量与活血解毒方中剂量组、活血解毒方中剂量组与活血解毒方高剂量组之间无差异外，其余各组之间肠道菌群结构差异均具有统计学意义（

＜0.05或

＜0.01）。

结论

活血解毒方可调节NOD小鼠肠道菌群结构、促进有益菌的生长、加快菌群的恢复，这可能是其治疗干燥综合征的机制之一。

Abstract

Objective

To explore the possible mechanism of

Huoxue Jiedu Formula

（活血解毒方， HJF） in the treatment of Sjogren's syndrome.

Methods

Thirty-five NOD mice， a classic animal model of Sjogren's syndrome， were randomly divided into a model group， total glucosides of paeony （TGP） group， and HJF high， moderate and low dose group， with seven mice in each group； and seven C57BL/6J mice were set as normal group. The normal group and the model group were given 10 ml/kg of distilled water by gavage； the TGP group was administered with 234 mg/kg of TGP capsules by gavage， while the HJF high， moderate and low dose group were respectively given 62.4 g/（kg·d）， 31.2 g/（kg·d） and 15.6 g/（kg·d） of HJF by gavage. After 8 weeks， the pathological staining of the submandibular glands were observed and scored. Simultaneously， the high-throughput sequencing was used to detect the composition of the intestinal flora and the dominant strains， and the diversity analysis was performed.

Results

Compared to those of the normal group， the pathological score of the submandibular glands of the model group and the TGP group significantly increased （

＜0.01）； HE staining showed that the exocrine gland structure was damaged， and there were acinar atrophy with varied degrees and multifocal lymphocytic infiltration in the tissues of the model group； the above-mentioned pathological damages were reduced in all three HJR groups with scarce scattered lymphocyte infiltration unable to gather into a stove， and more reduction was seen in the HJR moderate and high dose group than in the low dose group. The phylum level analysis showed that the model group had decreased Verrucomicrobial abundance and increased TM7 phylum abundance compared to the normal group （

＜0.05）； the HJF low dose group had increased Deferrobacteria abundance compared to the model group （

＜0.05） and the TGP group （

＜0.05）. The genus level analysis showed that the model group had higher Odobacter abundance and lower Prevotella abundance compared to the normal group （

＜0.05 or

＜0.01）； the HJF high dose group had decreased Odobacter abundance compared to the low dose group （

＜0.01）. Strain screening based on differences between groups showed that the number of dominant strains of the normal group， the model group and the TGP group were 19， 6 and 1， respectively， while that of the HJF low， moderate and high dose groups were 6， 2 and 8. Alpha diversity analysis showed that the model group had decreased Faith_Pd index compared to the normal group （

＜0.05）， while the HJF low and moderate dose groups had increased Faith_Pd index than the model group （

＜0.01）. Beta diversity analysis showed that there were significant differences between any two of the six groups in the intestinal flora structure except that between HJF low and moderate dose groups， and that between HJF moderate and high dose groups （

＜0.05 or

＜0.01）.

Conclusion

HJF can regulate the intestinal flora structure of the NOD mice， promote the growth of the beneficial bacteria， and accelerate the recovery of the flora， which may explain the mechanism of HJF in the treatment of Sjogren's syndrome.

关键词

Keywords

references

MARSHALL LL ， STEVENS GA . Management of primary Sjögren's syndrome ［J］. Consult Pharm ， 2018 ， 33 （ 12 ）： 691 - 701 .

王瑞婷，陈雁飞，汪钰涵，等 . T细胞亚群在原发性干燥综合征发病机制中的研究进展［J］. 兰州大学学报（医学版）， 2020 ， 46 （ 6 ）： 45 - 50 .

VIVINO FB ， BUNYA VY ， MASSARO-GIORDANO G ， et al . Sjogren's syndrome： An update on disease pathogenesis， clinical manifestations and treatment ［J］. Clin Immunol ， 2019 ， 203 ： 81 - 121 . doi： 10.1016/j.clim. 2019. 04.009 http://dx.doi.org/10.1016/j.clim.2019.04.009 .

MOON J ， CHOI SH ， YOON CH ， et al . Gut dysbiosis is prevailing in Sjögren's syndrome and is related to dry eye severity ［J］. PLoS One ， 2020 ， 15 （ 2 ）： e0229029 . doi： 10.1371/journal.pone.0229029 http://dx.doi.org/10.1371/journal.pone.0229029

WU GL ， LU HF ， CHEN YL ， et al . Changes of intestinal microecology in patients with primary Sjogren's syndrome after therapy of yangyin yiqi huoxue recipe ［J］. Chin J Integr Med ， 2019 ， 25 （ 9 ）： 654 - 662 .

KIM J ， CHOI SH ， KIM YJ ， et al . Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye ［J］. Nutrients ， 2017 ， 9 （ 11 ）： 1166 .

杜欣颖，白云静，申洪波 . 胡荫奇从毒、瘀、虚论治原发性干燥综合征经验［J］. 中医杂志， 2020 ， 61 （ 18 ）： 1594 - 1597 .

徐江喜 . 活血解毒方治疗原发性干燥综合征瘀毒证的疗效评价［D］. 北京：北京中医药大学， 2019 .

徐叔云 . 药理实验方法学［M］. 北京：人民卫生出版社， 1982 ： 129 - 131 .

CUTLER LS ， GREINER DL ， ROZENSKI D . Experimental autoallergic sialadenitis in the LEW rat.Ⅱ．Target antigens are associated with cell surface and intracellular particulate fractions derived from the submandibular gland ［J］． Cell Immunol ， 1991 ， 135 （ 2 ）： 346 - 353 ．

OKUMURA R ， TAKEDA K . Roles of intestinal epithelial cells in the maintenance of gut homeostasis ［J］. Exp Mol Med ， 2017 ， 49 （ 5 ）： e338 . doi： 10.1038/emm. 2017.20 http://dx.doi.org/10.1038/emm.2017.20

SINGH M ， TELES F ， UZEL NG ， et al . Characterizing microbiota from Sjögren's syndrome patients ［J］. JDR Clin Trans Res， 2021 ， 6 （ 3 ）： 324 - 332 .

ANTONIO CO ， AURORA LI ， ISAAC PA ， et al . Connection between the gut microbiome， systemic inflammation， gut permeability and FOXP3 expression in patients with primary Sjögren's syndrome ［J］. Int J Mol Sci ， 2020 ， 21 （ 22 ）： 8733 .

王其凯，袁祥，周滢波，等 . 共刺激分子B7-H4对干燥综合征模型NOD鼠T细胞亚群的作用［J］. 中华疾病控制杂志， 2018 ， 22 （ 7 ）： 731 - 735 .

毛晓娟 . 干燥综合征患者外周血中Treg和Th17细胞绝对数量与肠道微生物菌落特征的相关性研究［D］. 太原：山西医科大学， 2020 .

王信，王健，郭文静，等 . 原发性干燥综合征患者肠道菌群特点分析［J］. 南方医科大学学报， 2020 ， 40 （ 7 ）： 949 - 957 .

蔡红蝶，宿树兰，郭建明，等 . 丹参对糖尿病肾损伤大鼠肠道菌群多样性的影响［J］. 中国中药杂志， 2021 ， 46 （ 2 ）： 426 - 435 .

戚宇琪 . 玄参-苍术对2型糖尿病大鼠的降糖增效作用及对肠道菌群结构的影响［D］. 太原：山西省中医药研究院， 2020 .

周祎青，郑裕华，陈颂，等 . 连翘对岭南湿热模型小鼠的作用及其肠道菌群变化的研究［J］. 中药新药与临床药理， 2019 ， 30 （ 6 ）： 678 - 685 .

彭金娥，韩雅馨，卢旭然，等 . 白芍总苷长期给药对胶原诱导型关节炎大鼠和正常大鼠肠道菌群影响的纵向研究［J］. 中药新药与临床药理， 2021 ， 32 （ 1 ）： 1 - 16 .

陆带果，王璐瑶，王贵红，等 . 白芍总苷胶囊联合硫酸羟氯喹治疗干燥综合征的临床效果［J］. 中国医药导报， 2019 ， 16 （ 36 ）： 115 - 118 .

LUO XM ， EDWARDS MR ， MU Q ， et al . Gut microbiota in human systemic lupus erythematosus and a mouse model of lupus ［J］. Appl Environ Microbiol ， 2018 ， 84 （ 4 ）： e02288-17 . doi： 10.1128/AEM.02288-17 http://dx.doi.org/10.1128/AEM.02288-17 .

HE Z ， KONG X ， SHAO T ， et al . Alterations of the gut microbiota associated with promoting efficacy of prednisone by bromofuranone in MRL/lpr mice ［J］. Front Microbiol ， 2019 ， 10 ： 978 . doi： 10.3389/fmicb. 2019. 00978 http://dx.doi.org/10.3389/fmicb.2019.00978 .

李媛 . GTF2I、GTF2IRD1和IL12A基因多态性与中国汉族人群系统性红斑狼疮的相关性研究［D］. 青岛：青岛大学， 2015 .

vAN DER MEULEN TA ， HARMSEN HJM ， VILA AV ， et al . Shared gut， but distinct oral microbiota composition in primary Sjögren's syndrome and systemic lupus erythematosus ［J］. J Autoimmun ， 2019 ， 97 ： 77 - 87 . doi： 10.1016/j.jaut.2018.10.009 http://dx.doi.org/10.1016/j.jaut.2018.10.009 .

谢杭谕 . 肠道菌群及其代谢产物短链脂肪酸和肠黏膜损伤标记物在HIV感染组和健康组的对比研究［D］. 泸州：西南医科大学， 2017 .

蒙丹丽，梁列新，宋怀宇 . 短链脂肪酸在肠道中的生理作用［J］. 中国临床新医学， 2018 ， 11 （ 2 ）： 198 - 202 .

KARAASLAN A ， SOYSAL A ， KEPENEKLI KE ， et al . Lactococcus lactis spp lactis infection in infants with chronic diarrhea： two cases report and literature review in children ［J］. J Infect Dev Ctries ， 2016 ， 10 （ 3 ）： 304 - 307 .

LEE JY ， SEO MY ， YANG J ， et al . Polymicrobial peritonitis with lactococcus lactis in a peritoneal dialysis patient ［J］. Chonnam Med J ， 2014 ， 50 （ 2 ）： 67 - 69 .

MIGNACCA SA ， DORE S ， SPURIA L ， et al . Intramammary infusion of a live culture of Lactococcus lactis in ewes to treat staphylococcal mastitis ［J］. J Med Microbiol ， 2017 ， 66 （ 12 ）： 1798 - 1810 .

MIAO M ， HAO Z ， GUO Y ， et al . Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjögren's syndrome ［J］. Ann Rheum Dis ， 2018 ， 77 （ 12 ）： 1838 - 1840 .

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Effect of Huoxue Jiedu Formula （活血解毒方） on Intestinal Flora in NOD Mice

DOI：10.13288/j.11-2166/r.2022.01.011

摘要

Abstract

关键词

Keywords

references