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火经汤通过TrkA/MKK3/6/p38通路抑制膝骨关节炎大鼠背根神经节中降钙素基因相关肽和瞬时受体电位香草酸亚型1的表达

Suppression of CGRP and TRPV1 Expression in Dorsal Root Ganglia of Knee Osteoarthritis Rats by Huojing Decoction via TrkA/MKK3/6/p38 Pathway.

作者信息

Jiang Xinchao, Guo Yinyin, Fang Mei, Wang Xin, Zhang Biao, Song Yi, Qian Jianxue

机构信息

Department of Pain Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People's Republic of China.

Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People's Republic of China.

出版信息

J Inflamm Res. 2024 Aug 13;17:5311-5326. doi: 10.2147/JIR.S472341. eCollection 2024.

DOI:10.2147/JIR.S472341
PMID:39157588
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11330260/
Abstract

OBJECTIVE

Knee osteoarthritis (KOA) is a chronic condition characterized by persistent pain that can lead to severe disability. In this study, we primarily investigated the analgesic effect of Huojing decoction on MIA-induced knee arthritis.

METHODS

The network pharmacology method was employed to acquire target information of Huojing decoction and KOA. MIA was intratibially injected to induce KOA pain in rats. Huojing decoction was then administered once daily via intragastric administration for 14 days. Pain level was assessed by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The levels of inflammatory cytokines were determined by ELISA and PCR. TRPV1 and CGRP were detected through immunohistochemistry. The protein expression of TrkA, MKK3/6 and p38 was assessed by Western blot.

RESULTS

Mechanical allodynia and thermal hyperalgesia were observed in KOA rats. The expression levels of inflammatory cytokines were significantly decreased after Huojing decoction infusion of KOA rats. TRPV1 and CGRP were reduced with treatment. Furthermore, the protein expressions of TrkA, MKK3/6 and p38 in the DRG of rats were significantly decreased.

CONCLUSION

Our data suggested that Huojing decoction can alleviate inflammation in KOA pain rats. Additionally, it can inhibit the expression of TrKA, MKK3/6 and p38 signaling pathways, indicating its analgesic effect on KOA pain rats.

摘要

目的

膝骨关节炎（KOA）是一种以持续性疼痛为特征的慢性疾病，可导致严重残疾。在本研究中，我们主要研究了火经汤对单碘乙酸钠（MIA）诱导的膝关节炎的镇痛作用。

方法

采用网络药理学方法获取火经汤和KOA的靶点信息。通过胫骨内注射MIA诱导大鼠KOA疼痛。然后通过灌胃方式每日给予火经汤一次，持续14天。通过爪部撤离阈值（PWT）和爪部撤离潜伏期（PWL）评估疼痛程度。通过酶联免疫吸附测定（ELISA）和聚合酶链反应（PCR）测定炎症细胞因子水平。通过免疫组织化学检测瞬时受体电位香草酸亚型1（TRPV1）和降钙素基因相关肽（CGRP）。通过蛋白质免疫印迹法评估酪氨酸激酶A（TrkA）、丝裂原活化蛋白激酶激酶3/6（MKK3/6）和p38的蛋白表达。

结果

在KOA大鼠中观察到机械性异常性疼痛和热痛觉过敏。火经汤灌胃KOA大鼠后，炎症细胞因子的表达水平显著降低。治疗后TRPV1和CGRP减少。此外，大鼠背根神经节中TrkA、MKK3/6和p38的蛋白表达显著降低。

结论

我们的数据表明，火经汤可减轻KOA疼痛大鼠的炎症。此外，它可抑制TrKA、MKK3/6和p38信号通路的表达，表明其对KOA疼痛大鼠具有镇痛作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/148a/11330260/2e1f8de057d3/JIR-17-5311-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/148a/11330260/24334398c4b4/JIR-17-5311-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/148a/11330260/f7c6a9b984a4/JIR-17-5311-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/148a/11330260/e5959ed1537a/JIR-17-5311-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/148a/11330260/2e1f8de057d3/JIR-17-5311-g0008.jpg

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