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基于“肠-肾轴”理论探讨益肾化湿颗粒改善糖尿病肾病的临床疗效及作用机制

艾珊珊 崔涛 周乐 申振 李伟 韩聪

艾珊珊, 崔涛, 周乐, 申振, 李伟, 韩聪. 基于“肠-肾轴”理论探讨益肾化湿颗粒改善糖尿病肾病的临床疗效及作用机制[J]. 南京中医药大学学报, 2022, 38(12): 1103-1109. doi: 10.14148/j.issn.1672-0482.2022.1103
引用本文: 艾珊珊, 崔涛, 周乐, 申振, 李伟, 韩聪. 基于“肠-肾轴”理论探讨益肾化湿颗粒改善糖尿病肾病的临床疗效及作用机制[J]. 南京中医药大学学报, 2022, 38(12): 1103-1109. doi: 10.14148/j.issn.1672-0482.2022.1103
AI Shan-shan, CUI Tao, ZHOU Le, SHEN Zhen, LI Wei, HAN Cong. Clinical Efficacy and Mechanism of Yishen Huashi Granules in Treating Diabetic Kidney Disease Based on the 'Gut-Kidney Axis' Theory[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(12): 1103-1109. doi: 10.14148/j.issn.1672-0482.2022.1103
Citation: AI Shan-shan, CUI Tao, ZHOU Le, SHEN Zhen, LI Wei, HAN Cong. Clinical Efficacy and Mechanism of Yishen Huashi Granules in Treating Diabetic Kidney Disease Based on the "Gut-Kidney Axis" Theory[J]. Journal of Nanjing University of traditional Chinese Medicine, 2022, 38(12): 1103-1109. doi: 10.14148/j.issn.1672-0482.2022.1103

基于“肠-肾轴”理论探讨益肾化湿颗粒改善糖尿病肾病的临床疗效及作用机制

doi: 10.14148/j.issn.1672-0482.2022.1103
基金项目: 

国家自然科学基金青年科学基金项目 82204886

中国博士后科学基金面上项目 2021M702039

山东省中医药科技项目 2020Q012

“益肾化湿颗粒”临床应用研究和基础研究开放课题 2020367

详细信息
    作者简介:

    艾珊珊, 女, 助理实验师, E-mail: Aishan97s@163.com

    通讯作者:

    李伟, 女, 主任医师, 从事中西医结合治疗肾系疾病的研究, E-mail: lweidw@163.com

    韩聪, 男, 主治医师, 从事中西医结合治疗肾系疾病的研究, E-mail: 1585285585@qq.com

  • 中图分类号: R587.2

Clinical Efficacy and Mechanism of Yishen Huashi Granules in Treating Diabetic Kidney Disease Based on the "Gut-Kidney Axis" Theory

  • 摘要:   目的  观察益肾化湿颗粒治疗糖尿病肾病(DKD)的临床疗效, 探讨其通过“肠-肾轴”改善DKD的作用机制。  方法  100例DKD脾虚湿盛证患者随机分为试验组和对照组, 每组50例。对照组予西医基础治疗, 试验组在对照组治疗基础上加服益肾化湿颗粒。8周后观察2组患者中医证候积分、尿蛋白肌酐比值(UACR)、空腹血糖(FBG)、糖化血红蛋白(HbA1C)、血肌酐(Scr)、尿素氮(BUN)、肾小球滤过率(eGFR)、白蛋白(ALB)、超氧化物歧化酶(SOD)、白介素-6(IL-6)及尿N-乙酰-β氨基葡萄糖苷酶(NAG)含量的变化。并随机收集其中60例患者(试验组和对照组各30例)治疗后的粪便样本行16S rDNA V3+V4区测序筛选益肾化湿颗粒的作用靶菌。  结果  治疗后, 试验组的总有效率明显优于对照组(P<0.05);2组中医证候积分明显改善,试验组优于对照组(P<0.05,P<0.01);2组UACR、BUN、HbA1C、IL-6水平较治疗前明显降低(P<0.05,P<0.01), 试验组优于对照组(P<0.05,P<0.01);试验组SOD活性、ALB水平明显升高(P<0.05,P<0.01),优于对照组(P<0.05,P<0.01);与对照组比较, 试验组菌群多样性及丰度升高, 菌群的聚合度增加, F/B值下降; LEfSe分析发现试验组的优势属种是副拟杆菌属、长双歧杆菌、黏膜乳杆菌。  结论  益肾化湿颗粒可有效改善DKD脾虚湿盛证患者的中医临床证候, 降低血糖, 减少蛋白尿, 整体调节氧化应激及炎症水平并稳定肾功能, 影响肠道菌群的分布, 为进一步研究益肾化湿颗粒通过肠道菌群评估DKD的发生、发展和治疗提供了依据。

     

  • 图  1  测序质量及物种注释分析

    注: A.样品稀释曲线; B.物种累积箱型图; N.对照组; Y.试验组

    Figure  1.  Analysis of sequencing quality and species annotation

    图  2  菌群多样性分析

    注: A.Shannon指数组间差异条形图; B.Simpson指数组间差异条形图; C.组间PCoA比较图; D.2组前10菌门条形图; E.F/B值组间差异条形图; N.对照组; Y.试验组; 与对照组比较, *P<0.05。

    Figure  2.  Analysis of bacterial flora diversity

    图  3  组间差异比较

    注: A.属水平物种相对丰度柱状图; B.种水平物种相对丰度柱状图; C.LEfSe差异物种; N.对照组; Y.试验组

    Figure  3.  Comparison of differences between 2 groups

    表  1  2组患者治疗前后中医证候积分比较(x±s, n=50)

    Table  1.   Comparison of TCM syndrome scores between 2 groups before and after treatment(x±s, n=50)

    组别 时间 浮肿 疲倦乏力 食少纳呆 便溏 畏寒肢冷 腰脊酸痛 总积分
    试验组 治疗前 4.24±1.64 4.32±1.36 4.60±1.86 4.40±1.66 2.28±0.80 2.20±0.62 22.04±4.44
    治疗后 0.68±0.25**# 2.28±1.06**# 1.60±0.39**# 1.48±0.55**# 1.28±0.33**# 1.02±0.72** 8.60±3.12**##
    对照组 治疗前 3.56±1.04 4.40±1.34 4.84±1.34 4.28±1.40 2.00±0.85 1.90±0.71 20.98±5.31
    治疗后 1.24±0.50** 2.88±1.21** 2.36±1.09** 2.26±1.08** 1.76±0.87** 1.06±0.63** 11.58±4.64**
    注: 组内比较, * *P<0.01;组间比较, #P<0.05, # # P<0.01。
    下载: 导出CSV

    表  2  2组患者治疗前后生化指标情况比较[M(P25, P75), n=50]

    Table  2.   Comparison of biochemical indexes between 2 groups before and after treatment[M(P25, P75), n=50]

    组别 时间 UACR/(mg·g-1) Scr/(μmol·L-1) BUN/(mmol·L-1) FBG/(mmol·L-1) HbA1C/%
    试验组 治疗前 540(90, 1 120) 84.00(55.00, 113.50) 6.84(5.53, 9.79) 7.09(5.86, 8.04) 7.10(6.50, 8.23)
    治疗后 180(40, 580)**# 71.00(55.75, 109.00) 6.52(5.27, 7.76)** 6.72(5.43, 9.29) 6.75(6.20, 7.73)**#
    对照组 治疗前 350(80, 2 330) 72.50(53.75, 91.00) 6.74(5.92, 8.92) 7.54(6.67, 9.10) 7.70(7.00, 9.23)
    治疗后 340(100, 1 470)** 68.50(53.75, 89.00) 6.55(4.77, 8.31)* 7.44(5.97, 8.95) 7.35(6.69, 8.53)**
    注: 组内比较, *P<0.05, * *P<0.01;组间比较, #P<0.05。
    下载: 导出CSV

    表  3  2组患者治疗前后生化指标比较(x±s, n=50)

    Table  3.   Comparison of biochemical indexes between 2 groups before and after treatment(x±s, n=50)

    组别 时间 eGFR/(mL·min-1·1.73 m-2) NAG/(U·L-1) SOD/(U·mL-1) IL-6/(ng·L-1) ALB/(g·L-1)
    试验组 治疗前 82.09±25.96 22.63±6.65 151.48±25.22 23.55±2.05 39.40±4.34
    治疗后 83.32±24.32 21.53±6.99 161.36±22.65**# 21.35±1.98**# 41.02±3.49*##
    对照组 治疗前 87.68±23.63 22.30±6.80 147.72±20.09 23.53±1.73 37.54±5.49
    治疗后 87.55±23.31 21.06±5.70 152.14±23.39 22.21±2.15** 38.36±6.14
    注: 组内比较, *P<0.05, * *P<0.01;组间比较, #P<0.05, ##P<0.01。
    下载: 导出CSV

    表  4  2组患者临床疗效比较(n=50)

    Table  4.   Comparison of clinical efficacy between 2 groups (n=50)

    组别 显效 有效 无效 总有效率/%
    试验组 16 26 8 84#
    对照组 17 15 18 64
    注: 2组比较,χ2=5.198, #P<0.05。
    下载: 导出CSV
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  • 收稿日期:  2022-04-20
  • 网络出版日期:  2022-12-15
  • 发布日期:  2022-12-10

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