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茵陈蒿汤治疗胆汁淤积的临床前证据:动物研究的系统评价和荟萃分析。

Preclinical evidence of Yinchenhao decoction on cholestasis: A systematic review and meta-analysis of animal studies.

机构信息

Hospital of Chengdu University of Traditional Chinese Medicine, School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

School of Pharmacy, Provincial and State Key Laboratory Breeding Base of System Research, Development and Utilization of Chinese Herbal Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Phytother Res. 2021 Jan;35(1):138-154. doi: 10.1002/ptr.6806. Epub 2020 Sep 25.

Abstract

Cholestasis is an important cause of liver fibrosis and cirrhosis. Yinchenhao decoction has been used as a well-known traditional Chinese medicine used in the treatment of cholestasis for over 2,000 years. The purpose of this systematic review is to evaluate the preclinical evidence of Yinchenhao decoction on cholestasis models. The following databases were searched from inception to February 2020. Chinese National Knowledge Infrastructure, VIP medicine information system, Wanfang Database, PubMed, Web of Science, Embase and the Cochrane Library were searched. The content concerned Yinchenhao decoction on different animal model experiments for the treatment of cholestasis. The methodological quality of the included studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Animal Experiment Bias Risk Assessment Tool. A meta-analysis was conducted with RevMan 5.3 software according to the Cochrane tool. Nineteen studies on a total of 404 animals were included with five kinds of experimental animal models. The results showed that serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin and total bile acid in the group treated with Yinchenhao decoction were significantly lower than those in the model group (P < 0.00001). The alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase levels in the Yinchenhao decoction group were also significantly reduced (P < 0.00001). The subgroup analysis of the different models showed that Yinchenhao decoction had a significant effect on the bile duct ligation model, and there was a significant reduction in TBIL, DBIL and ALT levels (P < 0.00001) in ANIT-induced cholestasis. After 24 hours of Yinchenhao decoction treatment, there was no significant difference in TBIL levels (P = 0.34), but after 48 and 72 hours of treatment, the TBIL levels were significantly reduced compared with the model group (P < 0.00001). There was no significant difference in DBIL after 48 hours of administration (P = 0.26), but compared with the model group, Yinchenhao decoction could significantly reduce the DBIL levels after 48 hours of treatment (P < 0.0003). Yinchenhao decoction could significantly reduce the ALT levels after 24, 48 and 72 hours (P < 0.006). Yinchenhao decoction was able to significantly reduce the levels of TBIL, DBIL and ALT on different rat species: Wistar and Sprague Dawley (P = 0.0001; P = 0.0002). The preclinical evidence indicated that Yinchenhao decoction might be a potent and promising agent for cholestasis. Moreover, this conclusion should be further confirmed with more well-designed researches.

摘要

胆汁淤积是肝纤维化和肝硬化的一个重要原因。茵陈蒿汤作为一种著名的中药,用于治疗胆汁淤积已有 2000 多年的历史。本系统评价的目的是评估茵陈蒿汤治疗胆汁淤积模型的临床前证据。从建库到 2020 年 2 月,检索了以下数据库。中文科技期刊数据库、维普医药信息系统、万方数据库、PubMed、Web of Science、Embase 和 Cochrane 图书馆都进行了检索。内容涉及茵陈蒿汤在不同动物模型实验中治疗胆汁淤积的情况。根据 SYstematic Review Center for Laboratory animal Experimentation Animal Experiment Bias Risk Assessment Tool,对纳入研究的方法学质量进行了评估。采用 RevMan 5.3 软件对符合纳入标准的研究进行荟萃分析。共纳入 19 项研究,总计 404 只动物,涉及 5 种实验动物模型。结果表明,茵陈蒿汤治疗组血清总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素和总胆汁酸明显低于模型组(P < 0.00001)。茵陈蒿汤组丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶和碱性磷酸酶水平也明显降低(P < 0.00001)。不同模型的亚组分析表明,茵陈蒿汤对胆管结扎模型有显著影响,TBIL、DBIL 和 ALT 水平显著降低(P < 0.00001)。在 ANIT 诱导的胆汁淤积中,茵陈蒿汤治疗 24 小时后 TBIL 水平无显著差异(P = 0.34),但治疗 48 和 72 小时后 TBIL 水平明显低于模型组(P < 0.00001)。DBIL 水平在给药 48 小时后无显著差异(P = 0.26),但与模型组相比,茵陈蒿汤在治疗 48 小时后能明显降低 DBIL 水平(P < 0.0003)。茵陈蒿汤治疗 24、48 和 72 小时后可显著降低 ALT 水平(P < 0.006)。茵陈蒿汤可显著降低不同大鼠种属的 TBIL、DBIL 和 ALT 水平:Wistar 和 Sprague Dawley(P = 0.0001;P = 0.0002)。临床前证据表明,茵陈蒿汤可能是一种有效的、有前途的胆汁淤积治疗药物。然而,这一结论还需要更多设计良好的研究进一步证实。

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