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用于治疗小鼠弱精子症的不同加工产品的比较。

Comparison of different processed products of for the treatment of mice asthenozoospermia.

作者信息

Wu Wenhui, Guo Xiaohong, Li Jie, Yang Min, Xiong Yongai

机构信息

Institute of Chinese Pharmaceutical Preparations, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.

Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, China.

出版信息

Transl Androl Urol. 2024 Oct 31;13(10):2209-2228. doi: 10.21037/tau-24-274. Epub 2024 Oct 28.

DOI:10.21037/tau-24-274
PMID:39507862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11535743/
Abstract

BACKGROUND

improves sexual function and is used in the treatment of impotence and spermatorrhea. However, its chemical composition and mechanism of action remain unclear. This study investigates the chemical composition and mechanism of action of co-processed with salt and wine (GZP) in modulating testicular mitochondrial autophagy for the treatment of asthenozoospermia in mice.

METHODS

Adenine gavage + cyclophosphamide intraperitoneal injection was used to establish the model of asthenozoospermia, and six processed products were compared in the pharmacological efficacy for the treatment of asthenozoospermia in mice. The liquid chromatograph mass spectrometer (LC-MS) assay was performed to analyse the compositional changes in the GZP. The mechanism of GZP in the treatment of asthenozoospermia in mice was further investigated. The mitophagy was detected by transmission electron microscope (TEM) and immunofluorescence, respectively. Reactive oxygen species (ROS) were detected by probe. Protein expression was determined by Western blotting.

RESULTS

GZP exhibited optimal therapeutic effects on asthenozoospermia in mice. It showed the best therapeutic effect in improving the total number of spermatozoa, sperm survival rate, improving sperm viability and reducing sperm deformity rate, alleviating the abnormal pathological morphology of mice testis, and increasing the serum testosterone (T), follicle-stimulating hormone (FSH) and prolactin (PRL) levels in mice. The LC-MS detection found that Allicin showed the most significant increase in GZP. Besides, GZP reduced ROS level and inhibited mitophagy in mice testicular tissues. Meanwhile, it restrained the expression of PINK1, Parkin, Light chain 3II (LC3-II)/Light chain 3I (LC3-I) and Caspase-3 proteins.

CONCLUSIONS

GZP improves asthenozoospermia via inhibiting excessive mitophagy and protects the integrity of mitochondria by blocking the PINK1/Parkin signaling pathway. During which, the Allicin may play an important role.

摘要

背景

可改善性功能,用于治疗阳痿和遗精。然而,其化学成分和作用机制尚不清楚。本研究探讨盐酒共制(GZP)调节睾丸线粒体自噬治疗小鼠弱精子症的化学成分及作用机制。

方法

采用腺嘌呤灌胃+环磷酰胺腹腔注射建立弱精子症模型,比较6种炮制品对小鼠弱精子症的药理疗效。采用液相色谱-质谱联用(LC-MS)法分析GZP的成分变化。进一步研究GZP治疗小鼠弱精子症的机制。分别通过透射电子显微镜(TEM)和免疫荧光检测线粒体自噬。用探针检测活性氧(ROS)。通过蛋白质免疫印迹法测定蛋白质表达。

结果

GZP对小鼠弱精子症具有最佳治疗效果。在提高精子总数、精子存活率、改善精子活力和降低精子畸形率、减轻小鼠睾丸异常病理形态以及提高小鼠血清睾酮(T)、促卵泡生成素(FSH)和催乳素(PRL)水平方面显示出最佳治疗效果。LC-MS检测发现,GZP中大蒜素增加最为显著。此外,GZP降低了小鼠睾丸组织中的ROS水平并抑制了线粒体自噬。同时,它抑制了PINK1、Parkin、轻链3II(LC3-II)/轻链3I(LC3-I)和半胱天冬酶-3蛋白的表达。

结论

GZP通过抑制过度的线粒体自噬改善弱精子症,并通过阻断PINK1/Parkin信号通路保护线粒体的完整性。在此过程中,大蒜素可能起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/279ee85b07a3/tau-13-10-2209-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/0e47ee2794a7/tau-13-10-2209-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/0310ec93f765/tau-13-10-2209-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/822720e71f2a/tau-13-10-2209-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/e189ee3b8184/tau-13-10-2209-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/b20f2f36fec8/tau-13-10-2209-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/e10bb0057f2c/tau-13-10-2209-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/baf811937131/tau-13-10-2209-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/85888d28460b/tau-13-10-2209-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/279ee85b07a3/tau-13-10-2209-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/0e47ee2794a7/tau-13-10-2209-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/0310ec93f765/tau-13-10-2209-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/822720e71f2a/tau-13-10-2209-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/e189ee3b8184/tau-13-10-2209-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/b20f2f36fec8/tau-13-10-2209-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/e10bb0057f2c/tau-13-10-2209-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/baf811937131/tau-13-10-2209-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/85888d28460b/tau-13-10-2209-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7e/11535743/279ee85b07a3/tau-13-10-2209-f9.jpg

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本文引用的文献

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Mitochondria-associated programmed cell death as a therapeutic target for age-related disease.线粒体相关的程序性细胞死亡作为与年龄相关疾病的治疗靶点。
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The mitophagy pathway and its implications in human diseases.
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Parkin and mitochondrial signalling.帕金蛋白与线粒体信号传导
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Qiangjing tablets ameliorate asthenozoospermia via mitochondrial ubiquitination and mitophagy mediated by LKB1/AMPK/ULK1 signaling.强精片通过 LKB1/AMPK/ULK1 信号通路介导的线粒体泛素化和自噬改善弱精子症。
Pharm Biol. 2023 Dec;61(1):271-280. doi: 10.1080/13880209.2023.2168021.
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Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation.细胞线粒体自噬:机制、在疾病中的作用和小分子药物调节。
Theranostics. 2023 Jan 1;13(2):736-766. doi: 10.7150/thno.79876. eCollection 2023.
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