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| Celastrol Alleviates Pain in Rats with Gouty Arthritis by Promoting Autophagy via the AMPK/mTOR Signaling Pathway |
| WU Yuheng, LI Huan, GUO Bo, et al |
| Sichuan Fourth People's Hospital, Sichuan Chengdu 610011, China |
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Abstract Objective: To explore the effects of Celastrol on the pain in rats with acute Gouty arthritis (GA), and its mechanism of promoting autophagy through AMPK)/ mTOR signaling pathway. Methods: GA rat model was established by injecting Monosodium urate (MSU) into articular cavity. Totally 60 models were randomly divided into model group, Celastrol low-dose group (1g/kg Celastrol solution by gavage), Celastrol high-dose group (2g/kg Celastrol solution by gavage) and Compound C group (AMPK pathway inhibitor, 2mg/kg Celastrol solution by gavage+15mg/kg Compound C solution by intraperitoneal injection), with 15 rats in each group. Fifteen more SD rats were randomly selected as the control group (equal volume of normal saline was injected into the right posterior ankle joint). After the treatment, the swelling degree of ankle joint of rats in each group was detected by vernier caliper, and the gait and inflammatory index were scored. Von Frey Hair fiber was used to detect the mechanical pain threshold of rats in each group. The levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in rat serum were detected by enzyme-linked immunosorbent assay. HE staining was used to observe the histopathological changes of synovial tissue of ankle joint and score the degree of inflammatory infiltration. Western Blot was used to detect the expression levels of autophagy-related proteins Beclin-1, LC3Ⅱ/LC3Ⅰ and AMPK/mTOR signaling pathway-related proteins in ankle joints. Results: In the model group, the ankle joint structure was severely damaged, synovium proliferated, joint histopathological score, joint swelling, gait score, inflammatory index score, SP, CGRP and p-mTOR increased significantly (P<0.05), while mechanical pain threshold, Beclin-1, LC3Ⅱ/LC3Ⅰ, p-AMPK and p-ULK-1 decreased significantly (P Compared with the model group, the pathological injury of ankle joint of rats in low and high doses of Celastrol and Compound C group was obviously improved, and the joint histopathological score, joint swelling, gait score, inflammatory index score, SP, CGRP and p-mTOR were significantly reduced (P<0.05), and the mechanical pain threshold, Beclin-1, LC3Ⅱ/LC3Ⅰ, p-AMPK and P-MTOR were significantly reduced. Compared with the low-dose Celastrol group, the pathological score of joint tissue, joint swelling, gait score, inflammatory index score, SP, CGRP and p-mTOR in the high-dose Celastrol group and Compound C group decreased significantly (P<0.05), while the mechanical pain threshold, Beclin-1, LC3II/LC3I, p-AMPK and p-ULK-1 increased significantly. Compared with the high-dose Celastrol group, Compound C group reversed this result. Conclusion: Celastrol can inhibit the secretion of pain mediators and improve the pain symptoms of acute GA rats, and its mechanism is related to activating AMPK/mTOR pathway to promote autophagy.
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2025, Vol. 31 
