The Ameliorative Effect of Mahuang Fuzi and Shenzhuo Decoction on Membranous Nephropathy of Rodent Model is Associated With Autophagy and Wnt/β-Catenin Pathway.
The Ameliorative Effect of Mahuang Fuzi and Shenzhuo Decoction on Membranous Nephropathy of Rodent Model is Associated With Autophagy and Wnt/β-Catenin Pathway.
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DOI：
10.3389/fphar.2022.820130
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发表时间：
2022
影响因子：
5.6
通讯作者：
Liu, Baoli
中科院分区：
文献类型：
--
作者：
Gao, Yu;Dai, Haoran;Zhang, Na;Jiang, Hanxue;Zhang, Zihan;Feng, Zhendong;Dong, Zhaocheng;Liu, Wenbin;Liu, Fei;Dong, Xuan;Zhao, Qihan;Zhou, Xiaoshan;Du, Jieli;Zhang, Naiqian;Rui, Hongliang;Liu, Baoli
关键词：
膜性肾病（MN）发病率的增加使其成为我国成人原发性肾病综合征中最常见的病理类型。根据中医理论，麻黄附子和神浊汤可用于治疗此类疾病。我们用MFSD治疗MN患者，观察到与糖皮质激素和/或免疫抑制剂相当的疗效。本研究观察了MFSD对被动型Heymann肾炎（PHN）大鼠模型的治疗作用。我们的研究结果表明，MFSD治疗显著降低PHN大鼠的尿蛋白水平和足细胞损伤，并相应地改善肾脏病理，与环孢素A（CsA）单独的改善MN的效果。为探讨MFSD的潜在治疗机制，采用高效液相色谱-质谱联用技术（HPLC-MS）对MFSD的主要化学成分进行了分析。MFSD的活性成分约有30种。其次，基于网络药理学方法，筛选出MSFD作用于MN的相关靶点，为MFSD活性化合物的研究提供了初步的认识。聚类分析显示其活性位点可能位于自噬相关蛋白和Wnt/β-catenin通路中，与足细胞损伤有关。最后，我们在PHN大鼠模型中观察到MSFD治疗后肾脏自噬的改善和Wnt/β-连环蛋白途径的下调。本研究提示，自噬和Wnt/β-catenin通路可能是MFSD治疗MN的潜在靶点。
The increased incidence of membranous nephropathy (MN) has made it the most common pathological type of primary nephrotic syndrome in adults in China. According to the theory of Traditional Chinese Medicine (TCM), Mahuang Fuzi (Chinese ephedra and Radix Aconiti Lateralis Preparata) and Shenzhuo Decoction (MFSD) could be used to treat such diseases. We treated patients of MN with MFSD, and observed comparable efficacy to glucocorticoid and/or immunosuppressants. In this study, we observed the therapeutic effect of MFSD on the rat model of passive Heymann nephritis (PHN), a classical MN model. Our results showed that MFSD treatment significantly reduced urinary protein level and podocyte injury in PHN rats, and correspondingly improved renal pathology, with the improvement effect on MN comparable to that of Cyclosporine A (CsA) alone. To explore the potential therapeutical mechanism of MFSD, the main chemical components of MFSD were determined by High-performance liquid chromatography-mass spectrometry (HPLC-MS). There were about 30 active components of MFSD. Next, based on network pharmacology methods, we screened related targets of MSFD on MN, which provided a preliminary understanding of the MFSD bioactive compounds. The clustering analysis showed that its active site might be in the autophagy-related protein and Wnt/β-catenin pathway, which was related to podocyte injury. Finally, we observed an improvement in renal autophagy and a down-regulation of the Wnt/β-catenin pathway after MSFD treatment in a PHN rat model. According to this study, autophagy and Wnt/β-catenin pathway may be potential targets for MFSD in the treatment of MN.
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DOI：
10.1038/nrneph.2016.54
发表时间：
2016-07
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Edeling M;Ragi G;Huang S;Pavenstädt H;Susztak K
通讯作者：
Susztak K
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
影响因子：
21.3
作者：
Gatica D;Lahiri V;Klionsky DJ
通讯作者：
Klionsky DJ
溶酶体依赖性自噬途径的阻断导致特发性膜性肾病中补体膜攻击复合物诱导的足细胞损伤
影响因子：
4.6
作者：
Liu WJ;Li ZH;Chen XC;Zhao XL;Zhong Z;Yang C;Wu HL;An N;Li WY;Liu HF
通讯作者：
Liu HF