Effects of Shenling Baizhu Granule combined with pivilium bromide on immune function, intestinal flora and brain intestinal peptide in irritable bowel syndrome with predominant diarrhea
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摘要: 目的 探讨参苓白术颗粒联合匹维溴铵对腹泻型肠易激综合征(irritable bowel syndrome with predominant diarrhea，IBS-D)患者免疫功能、肠道菌群及脑肠肽的影响。方法 选取2018年2月—2021年9月收治的168例IBS-D患者为研究对象，随机分为观察组和对照组，每组84例。对照组服用匹维溴铵治疗，观察组在对照组基础上采用参苓白术颗粒治疗。比较两组患者的疗效、免疫功能、肠道菌群、脑肠肽及不良反应。结果 观察组有效率(90.48%)高于对照组(73.81%)，差异有统计学意义(χ2=8.207，P=0.042)。治疗后，观察组的免疫球蛋白A(immunoglobulin A，IgA)、免疫球蛋白M(immunoglobulin M，IgM)、CD3+、CD4+和CD4+/CD8+水平均显著高于对照组(t=7.955、8.371、9.712、7.684、4.817，P < 0.001)。治疗后，观察组的双歧杆菌、乳酸杆菌、拟杆菌的菌落数水平明显高于对照组(t=4.256、5.328、4.007，P < 0.001)，肠杆菌和肠球菌的菌落数水平明显低于对照组(t=-4.764、-8.083，P < 0.001)。观察组治疗后的神经生长因子(nerve growth factor，NGF)、脑源性神经营养因子(brain-derived neurotrophic factor，BDNF)、5-羟色胺(5-hydroxytryptamine，5-HT)和P物质(substance P，SP)水平明显低于对照组(t=-9.639、-13.529、-17.321、-16.902，P < 0.001)。分层线性回归表明，参苓白术颗粒使男性患者的双歧杆菌、乳酸杆菌、拟杆菌的暴露风险上升了21%、32%和36%，使肠杆菌和肠球菌的暴露风险下降了33%和25%；参苓白术颗粒使女性患者的双歧杆菌、乳酸杆菌、拟杆菌的暴露风险上升了23%、29%和32%，使肠杆菌和肠球菌的暴露风险下降了37%和22%。不同性别和组别之间无明显交互效应(P=0.376、0.283、0.197、0.356、0.241)。结论 参苓白术颗粒能够提高IBS-D患者的疗效，增强免疫功能，调节肠道菌群，降低血清NGF、BDNF水平，有很好的临床应用价值。Abstract: Objective To investigate the effects of Shenling Baizhu Granule combined with pivectium bromide on intestinal flora and serum nerve growth factor(NGF) and brain-derived neurotrophic factor(BDNF) in patients of irritable bowel syndrome with predominant diarrhea(IBS-D).Methods A total of 168 IBS-D patients admitted to our hospital from February 2018 to September 2021 were randomly divided into observation group and control group, with 84 cases in each group. The control group was treated with pivemonium bromide, and the observation group was treated with Shenling Baizhu Granule on the basis of the control group. The efficacy, immune function, intestinal flora, brain intestinal peptide and adverse reactions were compared between the two groups.Results The effective rate of observation group(90.48%) was higher than that of control group(73.81%), the difference was statistically significant(P=0.042). After treatment, the levels of immunoglobulin A(IgA), immunoglobulin M(IgM), CD3+, CD4+and CD4+/CD8+in the observation group were significantly higher than those in the control group(t=7.955, 8.371, 9.712, 7.684 and 4.817, P < 0.001). After treatment, the colony number levels of bifidobacterial, lactobacillus and bacteroidetes in the observation group were significantly higher than those in the control group(t=4.256, 5.328 and 4.007, P < 0.001), while the colony number levels of enterobacteria and enterococcus were significantly lower than those in the control group(t=-4.764 and-8.083, P < 0.001). The levels of NGF, BDNF, 5-hydroxytryptamine(5-HT) and substance P(SP) in the observation group were significantly lower than those in the control group after treatment(t=-9.639, -13.529, -17.321 and -16.902, P < 0.001). Hierarchical linear regression showed that Shenmai injection increased the exposure risk of bifidobacteria, Lactobacillus and Bacteroidetes by 21%, 32% and 36% in male patients, and decreased the exposure risk of enterobacteria and enterococcus by 33% and 25%. Shenmai injection increased the exposure risk of bifidobacterial, Lactobacillus and Bacteroidetes by 23%, 29% and 32%, and decreased the exposure risk of enterobacteria and enterococcus by 37% and 22%. There was no significant interaction effect between different genders and groups(P=0.376, 0.283, 0.197, 0.356 and 0.241).Conclusion Shenling Baizhu Granule can improve the curative effect of IBS-D patients, enhance immune function, regulate intestinal flora, and reduce serum levels of NGF and BDNF, which has good clinical application value.
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表 1 两组患者的临床资料比较
X±S，例 临床资料 观察组
(84例)对照组
(84例)t/χ2 P 年龄/岁 40.3±10.3 40.2±10.3 0.753 0.452 性别 0.226 0.824 男 41 40 女 43 44 BMI 25.9±3.1 24.8±3.1 0.902 0.368 受教育年限/年 9.7±1.2 9.7±1.2 0.553 0.582 病程/月 0.788 0.674 < 24 33 39 24~60 28 26 >60 23 19 
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表 2 两组临床疗效比较
例 组别 例数 治愈 显效 有效 无效 有效率/% χ2 P 观察组 84 21 26 29 8 90.48 8.207 0.042 对照组 84 17 19 26 22 73.81
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表 3 两组治疗前后免疫功能比较
X±S 时间 组别 例数 IgA/(g/L) IgM/(g/L) CD3+/% CD4+/% CD4+/CD8+ 治疗前 观察组 60 3.84±0.58 1.73±0.26 58.92±5.28 37.26±4.59 1.29±0.26 对照组 60 3.82±0.54 1.75±0.29 58.73±5.17 36.78±4.62 1.28±0.31 t 0.989 -0.831 0.057 0.593 0.973 P 0.317 0.412 0.948 0.567 0.328 治疗后 观察组 60 2.86±0.511) 1.41±0.341) 76.54±5.971) 49.56±5.671) 1.51±0.351) 对照组 60 2.12±0.461) 1.03±0.281) 68.97±5.751) 43.12±5.321) 1.24±0.321) t 7.955 8.371 9.712 7.684 4.817 P < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 与同组治疗前比较，1)P < 0.05。
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表 4 两组治疗前后肠道菌群比较
1gCFU/g，X±S 时间 组别 例数 双歧杆菌 乳酸杆菌 拟杆菌 肠杆菌 肠球菌 治疗前 观察组 84 8.23±1.28 7.30±1.11 8.36±1.49 8.72±1.78 7.27±1.05 对照组 84 8.07±1.18 7.19±1.16 8.73±1.58 8.99±1.60 7.24±1.15 t 0.833 0.609 -1.574 -1.027 0.226 P 0.406 0.544 0.117 0.306 0.821 治疗后 观察组 84 9.54±1.951) 8.77±1.731) 11.64±2.261) 7.47±1.031) 6.16±0.721) 对照组 84 8.38±1.581) 7.49±1.361) 10.27±2.181) 8.31±1.251) 7.07±0.731) t 4.256 5.328 4.007 -4.764 -8.083 P < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 与同组治疗前比较，1)P < 0.05。
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表 5 两组治疗前后脑肠肽水平比较
X±S 时间 组别 例数 NGF/(ng/L) BDNF/(pg/mL) 5-HT/(ng/mL) SP/(ng/mL) 治疗前 观察组 84 77.59±8.54 57.64±9.56 53.49±8.73 47.65±6.75 对照组 84 77.75±9.27 59.74±7.31 54.72±7.82 46.05±7.79 t -0.115 -1.603 -0.967 1.418 P 0.909 0.111 0.335 0.158 治疗后 观察组 84 55.47±9.191) 33.16±7.321) 30.51±5.711) 26.83±4.751) 对照组 84 69.28±8.281) 49.61±8.401) 47.85±7.181) 41.52±6.391) t -9.639 -13.529 -17.321 -16.902 P < 0.001 < 0.001 < 0.001 < 0.001 与同组治疗前比较，1)P < 0.05。
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表 6 两组不良反应情况比较
例 组别 例数 恶心呕吐 头晕 口干 总发生率/% χ2 P 观察组 84 0 2 3 5.95 0.097 0.755 对照组 84 1 3 2 7.14
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表 7 不同性别的分层线性回归
β值(95%CI) 性别 双歧杆菌 乳酸杆菌 拟杆菌 肠杆菌 肠球菌 男性 1.21(1.08~1.39)a) 1.32(1.04~1.59)a) 1.36(1.09~1.58)a) 0.67(0.34~0.89)a) 0.75(0.59~0.91)a) 女性 1.23(1.06~1.41)b) 1.29(1.02~1.63)b) 1.32(1.04~1.53)b) 0.63(0.31~0.84)b) 0.78(0.52~0.96)b) 交互效应P 0.376 0.283 0.197 0.356 0.241 注：a)以男性对照组为参照；b)以女性对照组为参照。
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[1] Wang ZY, Peng YL, Chen MS, et al. The prevalence of irritable bowel syndrome after severe acute respiratory syndrome coronavirus 2 infection and their association: a systematic review and meta-analysis of observational studies[J]. J Clin Med, 2023, 12(5): 1865. doi: 10.3390/jcm12051865
[2] Elwing JE, Atassi H, Rogers BD, et al. Emerging therapies in the management of irritable bowel syndrome(IBS)[J]. Expert Opin Emerg Drugs, 2022, 27(1): 55-73. doi: 10.1080/14728214.2022.2052043
[3] Rodrigues T, Rodrigues Fialho S, Araújo JR, et al. Procedures in fecal microbiota transplantation for treating irritable bowel syndrome: systematic review and meta-analysis[J]. J Clin Med, 2023, 12(5): 1725. doi: 10.3390/jcm12051725
[4] 尹德菲, 魏秀楠, 刘佳卉, 等. 理肠饮对腹泻型肠易激综合征患者肠道菌群及生活质量的影响[J]. 山东中医杂志, 2022, 41(9): 946-953. https://www.cnki.com.cn/Article/CJFDTOTAL-SDZY202209005.htm
[5] Li HY, Chen Y, Hu ZY, et al. Comparison of acupuncture and pinaverium bromide in the treatment of irritable bowel syndrome: a protocol for systematic review and meta-analysis[J]. Medicine (Baltimore), 2021, 100(16): e25604. doi: 10.1097/MD.0000000000025604
[6] 石洁. 参苓白术颗粒对肠道菌群的调节作用研究[J]. 北方药学, 2021, 18(1): 190-192. doi: 10.3969/j.issn.1672-8351.2021.01.089
[7] Drossman DA, Hasler WL. Rome Ⅳ-functional GI disorders: disorders of gut-brain interaction[J]. Gastroenterology, 2016, 150(6): 1257-1261. doi: 10.1053/j.gastro.2016.03.035
[8] 张声生, 魏玮, 杨俭勤. 肠易激综合征中医诊疗专家共识意见(2017)[J]. 中医杂志, 2017, 58(18): 1614-1620. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ201718024.htm
[9] 吴冬, 彭涛, 荣培晶, 等. 耳甲电针治疗腹泻型肠易激综合征的疗效[J]. 世界中医药, 2021, 16(11): 1721-1725. doi: 10.3969/j.issn.1673-7202.2021.11.015
[10] 张炜, 郑秀金, 陈长旦. 温肾健脾汤联合布拉氏酵母菌散对腹泻型肠易激综合征患者肠道微生态的影响[J]. 中国中西医结合消化杂志, 2022, 30(7): 514-517, 522. doi: 10.3969/j.issn.1671-038X.2022.07.10 https://zxyxh.whuhzzs.com/article/doi/10.3969/j.issn.1671-038X.2022.07.10
[11] 尹德菲, 魏秀楠, 刘佳卉, 等. 理肠饮治疗腹泻型肠易激综合征肝郁脾虚证的临床疗效及机制研究[J]. 南京中医药大学学报, 2022, 38(8): 687-695. https://www.cnki.com.cn/Article/CJFDTOTAL-NJZY202208006.htm
[12] So D, Quigley EMM, Whelan K. Probiotics in irritable bowel syndrome and inflammatory bowel disease: review of mechanisms and effectiveness[J]. Curr Opin Gastroenterol, 2023, 39(2): 103-109. doi: 10.1097/MOG.0000000000000902
[13] 孙茂秋, 卢冬雪, 李堃, 等. 健肠止泻合剂联合穴位贴敷治疗腹泻型肠易激综合征的临床观察和机制探索[J]. 中国中西医结合消化杂志, 2023, 31(10): 802-805, 809. doi: 10.3969/j.issn.1671-038X.2023.10.14 https://zxyxh.whuhzzs.com/article/doi/10.3969/j.issn.1671-038X.2023.10.14
[14] 冯雅婧, 何兴. 肠易激综合征患者肠道菌群与炎症反应及病情严重程度的关系分析[J]. 航空航天医学杂志, 2022, 33(10): 1178-1180. https://www.cnki.com.cn/Article/CJFDTOTAL-HKHT202210009.htm
[15] Vedantam S, Graff E, Khakoo NS, et al. Food as medicine: how to influence the microbiome and improve symptoms in patients with irritable bowel syndrome[J]. Curr Gastroenterol Rep, 2023, 25(3): 52-60. doi: 10.1007/s11894-023-00861-0
[16] 张文文, 齐峰. 肠易激综合征的研究进展[J]. 中外医学研究, 2022, 20(23): 181-184. https://www.cnki.com.cn/Article/CJFDTOTAL-YJZY202223046.htm
[17] 李旗, 田福玲, 郭振宇, 等. 浮针疗法对轻中度腹泻型肠易激综合征患者内脏敏感性、胃肠动力、肠道菌群及肠黏膜屏障功能的影响研究[J]. 中国全科医学, 2021, 24(9): 1111-1115, 1130. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202109039.htm
[18] Chunduri A, Reddy SDM, Jahanavi M, et al. Gut-brain axis, neurodegeneration and mental health: a personalized medicine perspective[J]. Indian J Microbiol, 2022, 62(4): 505-515.
[19] Qiao L, Chen Y, Song XF, et al. Selenium nanoparticles-enriched Lactobacillus casei ATCC 393 prevents cognitive dysfunction in mice through modulating microbiota-gut-brain axis[J]. Int J Nanomedicine, 2022, 17: 4807-4827. doi: 10.2147/IJN.S374024
[20] 李菊芳, 陈小芳, 徐惠明, 等. 痛泻要方治疗肠易激综合征伴焦虑抑郁(肝郁脾虚证)临床观察[J]. 光明中医, 2022, 37(20): 3717-3720. https://www.cnki.com.cn/Article/CJFDTOTAL-GMZY202220014.htm
[21] 赵耀, 刘兴山, 郑薇薇. 肝郁脾虚型肠易激综合征(腹泻型)中医治疗进展[J]. 实用中医内科杂志, 2022, 36(10): 58-61. https://www.cnki.com.cn/Article/CJFDTOTAL-SYZY202210019.htm
[22] Hu QR, Pan Y, Wu HC, et al. The ways for ginsenoside Rh2 to fight against cancer: the molecular evidencesin vitroandin vivo[J]. J Ginseng Res, 2023, 47(2): 173-182.
[23] Mohanan P, Yang TJ, Song YH. Genes and regulatory mechanisms for ginsenoside biosynthesis[J]. J Plant Biol, 2023, 66(1): 87-97.
[24] 祝丽娟, 文建英, 罗玉兰. 参苓白术颗粒联合布拉氏酵母菌治疗小儿功能性消化不良的临床疗效分析[J]. 现代消化及介入诊疗, 2021, 26(5): 624-627. https://www.cnki.com.cn/Article/CJFDTOTAL-XDXH202105019.htm
[25] 田由京, 陈兴超, 张浩, 等. 参苓白术颗粒联合美沙拉嗪对溃疡性结肠炎患者Th17/Treg细胞平衡的影响以及疗效分析[J]. 中国中西医结合消化杂志, 2019, 27(9): 703-706. https://zxyxh.whuhzzs.com/article/doi/10.3969/j.issn.1671-038X.2019.09.13
[26] 李娉娉. 参苓白术颗粒联合双歧杆菌三联活菌散治疗新生儿腹泻的效果[J]. 中国民康医学, 2023, 35(16): 125-127. https://www.cnki.com.cn/Article/CJFDTOTAL-ZMYX202316038.htm
[27] 钟伟恩, 叶红, 谭益秋, 等. 参苓白术颗粒联合西药治疗对抗生素相关性腹泻患儿免疫功能的影响[J]. 黑龙江医学, 2022, 46(4): 439-441. https://www.cnki.com.cn/Article/CJFDTOTAL-HLYX202204014.htm
[28] 郑厚胜, 郑斯文, 王英平, 等. 人参皂苷Rg3对环磷酰胺致免疫功能低下小鼠的免疫调节作用[J]. 中成药, 2021, 43(11): 3202-3206. https://www.cnki.com.cn/Article/CJFDTOTAL-ZCYA202111053.htm
[29] 李昶, 雷天荣, 王思明, 等. 人参蛋白对阿尔茨海默病小鼠肠道菌群及BDNF/TrkB信号通路的影响[J]. 中成药, 2023, 45(4): 1319-1323. https://www.cnki.com.cn/Article/CJFDTOTAL-ZCYA202304050.htm
[30] 庞博. 人参总蛋白对体内外PD模型的改善作用及对肠道微生物菌群的影响研究[D]. 长春: 长春中医药大学, 2022.
[31] 杨娟, 曹玉爽, 徐耀, 等. 丹酚酸B、人参皂苷Rg1及三七皂苷R1对氧糖剥夺/复氧复糖损伤星形胶质细胞的保护作用[J]. 中国药理学通报, 2022, 38(10): 1466-1472. https://www.cnki.com.cn/Article/CJFDTOTAL-YAOL202210006.htm
[32] 刘志杰, 毛会征, 林原, 等. 人参皂甙对急性肾衰大鼠中缝正中核和中缝背核5-HT含量的影响[J]. 神经解剖学杂志, 2018, 34(6): 732-736. https://www.cnki.com.cn/Article/CJFDTOTAL-SJJP201806014.htm
[33] 何频, 文静, 黄一. 人参皂苷Rb1对癫痫大鼠海马神经元损伤的影响[J]. 临床神经病学杂志, 2023, 36(4): 289-294. https://www.cnki.com.cn/Article/CJFDTOTAL-LCSJ202304010.htm
[34] 戚宇锋, 任来峰, 曹雪玲, 等. 山西省健康人群的肠道菌群组成特征及其与性别和年龄的关系[J]. 中国微生态学杂志, 2019, 31(10): 1117-1123. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWS201910001.htm
[35] 谢丹, 张沐诗, 陈春, 等. 基于性别二分类的青海天峻藏民肠道菌群差异分析[J]. 中国微生态学杂志, 2018, 30(12): 1379-1385, 1395. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWS201812004.htm
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