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通过AMPK途径调节骨关节炎大鼠肠道微生物群,Miya对骨骼肌变化的影响。

The effect of Miya on skeletal muscle changes by regulating gut microbiota in rats with osteoarthritis through AMPK pathway.

作者信息

Wang Sen, Duan Zhengwei, Li Zihua, Yang Dong, Lu Hengli, Zhang Yiwei, Fu Yuesong, Guan Yonghao, Li Guodong, Qian Feng, Xu Tianyang

机构信息

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Rd, Shanghai, 200072, People's Republic of China.

Department of Orthopedics, Bengbu First People's Hospital, Bengbu, Anhui, 233000, China.

出版信息

BMC Musculoskelet Disord. 2024 Dec 30;25(1):1081. doi: 10.1186/s12891-024-08203-5.

Abstract

BACKGROUND

The study aimed to explore whether Miya (MY), a kind of Clostridium butyricum, regulated osteoarthritis (OA) progression through adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway.

METHODS

The OA rats were orally given MY daily for 4 weeks and were intramuscularly injected with AMPK inhibitor once a week for 4 weeks. Hematoxylin eosin (HE) staining was used to observe the histological morphology of the knee joint. The levels of succinate dehydrogenase (SDH) and muscle glycogen (MG) in the tibia muscle of rats were detected by the corresponding kits, as well as the expression of related genes/proteins were assessed by real-time quantitative PCR (RT-qPCR) and western blot.

RESULTS

HE staining suggested that MY suppressed the symptoms of OA, which was abolished by AMPK inhibitor. Furthermore, the SDH and MG contents in the OA + MY + AMPK inhibitor group were lower than in the OA + MY group. At last, the levels of AMPK, PI3K, AKT1, Ldh, Myod, Chrna1, and Chrnd were notably decreased after AMPK inhibitor treatment, while the levels of Lcad and Mcad were up-regulated by AMPK inhibitor. Furthermore, their protein expression levels detected by western blot were consistent with those from RT-qPCR.

CONCLUSION

MY may partially regulate skeletal muscle changes and prevente OA development through the AMPK pathway.

摘要

背景

本研究旨在探讨丁酸梭菌的一种——米雅(MY)是否通过5'-单磷酸腺苷激活蛋白激酶(AMPK)途径调节骨关节炎(OA)的进展。

方法

给OA大鼠每日口服MY,持续4周,并每周一次肌肉注射AMPK抑制剂,持续4周。采用苏木精-伊红(HE)染色观察膝关节的组织形态学。用相应试剂盒检测大鼠胫骨肌肉中琥珀酸脱氢酶(SDH)和肌糖原(MG)的水平,并用实时定量PCR(RT-qPCR)和蛋白质印迹法评估相关基因/蛋白的表达。

结果

HE染色表明,MY可减轻OA症状,但AMPK抑制剂可消除这种作用。此外,OA + MY + AMPK抑制剂组的SDH和MG含量低于OA + MY组。最后,AMPK抑制剂处理后,AMPK、PI3K、AKT1、Ldh、Myod、Chrna1和Chrnd的水平显著降低,而Lcad和Mcad的水平则被AMPK抑制剂上调。此外,蛋白质印迹法检测的它们的蛋白表达水平与RT-qPCR结果一致。

结论

MY可能通过AMPK途径部分调节骨骼肌变化并预防OA发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e571/11684039/b909b34da642/12891_2024_8203_Fig1_HTML.jpg

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