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基于 1H NMR 的代谢组学揭示了龟龄集对老年大鼠睾丸功能障碍的保护作用。

H NMR-based metabolomics revealed the protective effects of Guilingji on the testicular dysfunction of aging rats.

机构信息

Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, 030006, PR China; Shanxi Institute for Food and Drug Control, Taiyuan, 030001, PR China.

Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, 030006, PR China.

出版信息

J Ethnopharmacol. 2019 Jun 28;238:111839. doi: 10.1016/j.jep.2019.111839. Epub 2019 Mar 27.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Guilingji (GLJ), a famous and classical traditional Chinese medicine (TCM) prescription, has been used to extend the lifespan and improve the life qualities of the elderly for hundreds of years in China.

AIM OF THE STUDY

We aimed to explore the protective effects of GLJ on the testicular dysfunction of aging rats, as well as the regulating effects of GLJ on the metabolic disturbance and metabolite changes in natural aging rats.

MATERIALS AND METHODS

Forty 23-month-old rats were divided randomly into four groups, including the old control group and three groups of GLJ treatment at 37.5, 75, and 150 mg/kg doses, respectively. Additionally, 10 four-month rats were included as the youth control group. Testicular dysfunction was first evaluated by measuring the changes in the wet weights of the testicles, concentration of serum testosterone (T), and morphologic changes of the testis. Subsequently, an H NMR-based metabolomics approach coupled with multivariate analysis, including partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to monitor the metabolite changes.

RESULTS

Compared with the old control group, the wet weights of the testicles and T concentration were significantly increased, while the morphologic abnormality of testicular tissues was improved by a 4-week treatment course with GLJ. Furthermore, compared with the old control group, the urinary levels of alanine, pantothenate, phenylalanine, β-hydroxybutyrate and pyruvate were significantly decreased after a 4-week treatment course with GLJ. Additionally, we found that amino acid metabolism and pyruvate metabolism were significantly involved in the regulatory effect of GLJ.

CONCLUSIONS

The current findings provided, for the first time, sound evidence of the protective effects of GLJ on testicular dysfunction from both biochemical and metabolomics perspectives. The mechanisms of GLJ could be related to regulating amino acid metabolism and pyruvate metabolism. The current study lays an important foundation for further research and for the broad clinical application of GLJ.

摘要

民族药理学相关性

龟龄集(GLJ)是一种著名的经典中药(TCM)方剂,在中国已有数百年的历史,用于延长老年人的寿命和提高生活质量。

研究目的

本研究旨在探讨 GLJ 对衰老大鼠睾丸功能障碍的保护作用,以及 GLJ 对自然衰老大鼠代谢紊乱和代谢物变化的调节作用。

材料和方法

将 40 只 23 月龄大鼠随机分为四组,包括老年对照组和 GLJ 处理组(37.5、75 和 150mg/kg 剂量),每组 10 只,以及 10 只 4 月龄大鼠作为青年对照组。首先通过测量睾丸湿重、血清睾酮(T)浓度和睾丸形态变化来评估睾丸功能障碍。随后,采用基于 H NMR 的代谢组学方法结合多元分析,包括偏最小二乘判别分析(PLS-DA)和正交偏最小二乘判别分析(OPLS-DA),监测代谢物变化。

结果

与老年对照组相比,GLJ 治疗 4 周后,睾丸湿重和 T 浓度显著增加,睾丸组织形态异常得到改善。此外,与老年对照组相比,GLJ 治疗 4 周后,大鼠尿液中丙氨酸、泛酸、苯丙氨酸、β-羟丁酸和丙酮酸水平显著降低。此外,我们发现氨基酸代谢和丙酮酸代谢与 GLJ 的调节作用显著相关。

结论

本研究首次从生化和代谢组学角度为 GLJ 对睾丸功能障碍的保护作用提供了有力证据。GLJ 的作用机制可能与调节氨基酸代谢和丙酮酸代谢有关。本研究为进一步研究和广泛临床应用 GLJ 奠定了重要基础。

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