Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease.

Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease.
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清热消症益气方缓解糖尿病肾病肾损伤并激活线粒体自噬

DOI:
10.3389/fphar.2022.992597
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发表时间:
2022
影响因子:
5.6
通讯作者:
Sun, Weiwei
Sun, Weiwei
中科院分区:
医学2区
文献类型:
--
作者:
Wu, Qiaoru;Yan, Runze;Yang, Hanwen;Wang, Yixuan;Zhang, Chao;Zhang, Jiale;Cui, Zhaoli;Wang, Yaoxian;Sun, Weiwei

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简介:清热消症益气方是治疗糖尿病肾病的有效方剂,我们通过临床试验证实了清热消症方治疗糖尿病肾病的疗效。本研究探讨清热消症益气方治疗糖尿病肾病的作用机制。方法:采用Vanquish UHPLCTM对清热消症益气方冻干粉进行化学成分分析。采用单侧肾切除加大剂量链脲佐菌素注射建立糖尿病肾病大鼠模型。检测糖尿病肾病大鼠的血尿素氮、血肌酐、血糖、总胆固醇、甘油三酯、血清总蛋白、白蛋白、丙氨酸氨基转移酶、天冬氨酸氨基转移酶和24 h尿总蛋白。采用HE、Masson染色、PAS染色及透射电镜观察肾脏病理变化。Western blot法检测细胞内纤维化相关蛋白和线粒体自噬相关蛋白的表达。本研究还采用免疫荧光共定位技术,进一步研究清热消症益气方对足细胞线粒体自噬的影响。结果:从清热消症益气方中初步鉴定出27种成分。我们发现PINK 1/Parkin介导的线粒体自噬在糖尿病肾病中受到抑制。清热消症益气方治疗可提高糖尿病肾病大鼠体重,降低肾指数,减少蛋白尿,改善糖脂代谢紊乱,减轻肾纤维化,降低Col Ⅳ和TGF-β1的表达。清热消症益气方治疗还可增加糖尿病肾病大鼠足细胞和高糖培养足细胞nephrin的表达,激活线粒体自噬,保护足细胞。结论:PINK 1/Parkin介导的线粒体自噬在糖尿病肾病中受到抑制,清热消症益气方治疗不仅可以改善糖尿病肾病的病理损伤,而且可以促进线粒体自噬,保护糖尿病肾病足细胞。
Introduction: Qing-Re-Xiao-Zheng-Yi-Qi Formula is an effective prescription in diabetic kidney disease treatment, we have confirmed the efficacy of Qing-Re-Xiao-Zheng therapy in diabetic kidney disease through clinical trials. In this study, we investigated the mechanisms of Qing-Re-Xiao-Zheng-Yi-Qi Formula in the treatment of diabetic kidney disease. Methods: We used Vanquish UHPLCTM to analyze the chemical profiling of Qing-Re-Xiao-Zheng-Yi-Qi Formula freeze-dried powder. We constructed diabetic kidney disease rat models induced by unilateral nephrectomy and high-dose streptozocin injection. We examined blood urea nitrogen, serum creatinine, serum glucose, total cholesterol, triglyceride, serum total protein, albumin, alanine aminotransferase, aspartate aminotransferase and 24 h urinary total protein in diabetic kidney disease rats. The renal pathological changes were observed by HE, Masson, PAS stanning and transmission electron microscopy. The levels of fibrosis-related proteins and mitophagy-related proteins were detected by western blot analysis. We also conducted an immunofluorescence co-localization analysis on podocytes to further investigate the effect of Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment on mitophagy. Results: A total of 27 constituents in Qing-Re-Xiao-Zheng-Yi-Qi Formula were tentatively identified. We found PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could raise body weight and reduce renal index, reduce proteinuria, improve glycolipid metabolic disorders, ameliorate renal fibrosis, and reduce the expression of Col Ⅳ and TGF-β1 in diabetic kidney disease rats. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could also increase the expression of nephrin, activate mitophagy and protect podocytes in diabetic kidney disease rats and high glucose cultured podocytes. Conclusion: PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease, and Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could not only ameliorate pathological damage, but also promote mitophagy to protect podocytes in diabetic kidney disease.
DOI: 10.1111/jcmm.15658
发表时间: 2020-09
影响因子: 5.3
作者:
Chen L;Feng P;Peng A;Qiu X;Lai W;Zhang L;Li W
通讯作者: Li W
DOI: 10.3892/ijmm.2021.4955
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DOI: 10.1002/ptr.6818
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影响因子: --
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DOI: 10.3390/biomedicines9050457
发表时间: 2021-04-22
期刊: Biomedicines
影响因子: 4.7
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DOI: 10.1681/asn.2014040405
发表时间: 2015-10-01
影响因子: 13.6
作者:
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通讯作者: He, John Cijiang