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基于血清代谢组学的黄雪益肾方改善慢性肾衰的机制研究

Clinical study on acupoint thread embedding combined with Wenshen Bugu Formula for treatment of aromatase inhibitor associated musculoskeletal symptoms in patients of postmenopausal breast cancer
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摘要 目的:评价黄雪益肾方治疗大鼠慢性肾衰的药效,并通过代谢组学初步揭示其代谢调控机制。方法:SD大鼠分为空白对照组、模型组、阳性药(缬沙坦)组和黄雪益肾方低、高剂量组。用阿霉素和腺嘌呤联合诱导慢性肾衰大鼠模型,空白组和模型组每日给予0.9%NaCl溶液,给药组分别给予缬沙坦8.33 mg/kg/d,黄雪益肾方12.5、25 g/kg/d灌胃,连续6周。实验期间监测大鼠一般情况、检测24 h尿蛋白及肾功能指标,苏木精-伊红(H-E)染色观察肾脏病理变化。通过超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用(UPLC-LTQ-Orbitrap-MS/MS)分析血清代谢变化,探索黄雪益肾方改善大鼠慢性肾衰的代谢调控机制。结果:与空白组比较,模型组大鼠出现体质量减少、精神萎靡、羸弱无力等衰竭症状,24 h尿蛋白显著升高,血肌酐(Scr)、尿素氮(BUN)显著升高(P<0.01),血清白蛋白(Alb)显著降低(P<0.01),药物干预后各指标均有不同程度改善(P<0.05,P<0.01)。病理结果显示,黄雪益肾方能有效改善模型组大鼠出现的肾小管损伤,间质纤维化及肾小球萎缩硬化等现象。代谢组学研究共鉴定出差异代谢物44个,主要富集于精氨酸生物合成、甘油磷脂代谢、花生四烯酸代谢、鞘脂代谢等代谢通路。结论:黄雪益肾方可明显减轻慢性肾衰大鼠尿蛋白现象,缓解肾功能损伤,主要效应机制涉及其对脂质代谢和炎症损伤的调节作用。 Objective:To observe the clinical efficacy of acupoint thread embedding(ATE)combined with Wenshen Bugu Formula for the treatment of aromatase inhibitor associated musculoskeletal symptoms(AIMSS)in postmenopausal women with breast cancer.Methods:A randomized controlled trial design was conducted.A total of 128 postmenopausal breast cancer patients with AIMSS were randomly divided into ATE combined with Chinese medicine group and Chinese medicine group,64 cases in each group.The patients in both groups were treated with Wenshen Bugu Formula decoction orally,and the patients in the ATE combined with Chinese medicine group were treated with ATE based on above.The treatment course of two groups was 12 weeks,and the patients were followed up for 12 weeks after the treatment course.Before treatment and at the 6th,12th,18th,and 24th weeks of treatment,the scores of Brief Pain InventoryShort Form(BPI-SF)and Functional Assessment of Cancer Therapy-Breast(FACT-B)in both groups were assessed.Before treatment and at the 12th and 24th weeks of treatment,the Morisky Medication Adherence Scale(MMAS-8)scores of the two groups were evaluated.Results:During the research,three cases were eliminated and 4 cases were shed off in the ATE combined with Chinese medicine group,and 1 case was eliminated and 6 cases were shed off in the Chinese medicine group.Finally,61 cases in the ATE combined with Chinese medicine group and 63 cases in the Chinese medicine group were included in the modified intention-to-treat(mITT)analysis.(1)After treatment,the scores of the Brief Pain Inventory-Worst Pain(BPI-WP),average pain,pain severity,and pain interference in both groups were significantly decreased compared with those before treatment(P<0.01).Compared with the Chinese medicine group,at the 12th,18th,and 24th weeks of treatment,the BPI-WP scores of the ATE combined with Chinese medicine group were significantly decreased(P<0.05),at the 12th and 18th weeks of treatment,the average pain scores and pain severity scores of the ATE combined with Chinese medicine group were significantly decreased(P<0.05),and at the 12th week of treatment,the pain interference scores of the ATE combined with Chinese medicine group were significantly decreased(P<0.05).(2)At the 6th,12th,18th,and 24th weeks of treatment,the FACT-B scores of both groups were significantly increased compared with those before treatment(P<0.01),and the score of the ATE combined with Chinese medicine group was higher than that of the Chinese medicine group(P<0.05).(3)At the 12th and 24th weeks of treatment,the MMAS-8 scores in both groups were significantly increased compared with those before treatment(P<0.01).However,no statistically significant difference on the score was observed between the two groups(P>0.05).Conclusion:Compared with Chinese medicine treatment alone,the traditional Chinese medicine comprehensive therapy of ATE combined with Wenshen Bugu Formula can more effectively alleviate joint pain for postmenopausal breast cancer patients with AIMSS,and enhance the quality of life,with persistent efficacy,which is worthy of clinical promotion.
作者 钱晓婧 陈颖 孙传玉 刘王振祖 李雪惠 林钐 胡诚 QIAN Xiaojing;CHEN Ying;SUN Chuanyu;LIU Wangzhenzu;LI Xuehui;LIN Shan;HU Cheng(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Traditional Chinese Medicine Integrated Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China;Nanxiang Hospital,Shanghai 201802,China;Huashan Hospital,Fudan University,Shanghai 200040,China)
出处 《上海中医药大学学报》 CAS 2024年第6期57-64,74,共9页 Academic Journal of Shanghai University of Traditional Chinese Medicine
基金 上海市名中医陈以平学术经验传承研究工作室(2022GYQY014) 虹口区卫生健康委员会临床重点专科建设(HKLCZD2024A02) 上海中医药大学科技发展项目(23KFL090)。
关键词 慢性肾衰 黄雪益肾方 血清代谢组学 代谢通路分析 chronic renal failure Huangxue Yishen Formula serum metabolomics metabolic pathway analysis
作者简介 钱晓婧,女,在读硕士生,主要从事特色中药复方物质基础与作用机制研究;通信作者:古胡诚,实验师,E-mail:hucheng10200@163.com。通信作者:林钐,主任医师,E-mail:chrislinshan@126.com。
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