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The Mechanism of Yiyaobi Ⅱ Mediating KLF2 Regulation of PI3K/Akt/mTOR Pathway on the Expression and Biological Behavior of Rheumatoid Arthritis Mouse Model |
ZHOU Shucheng, GU Lingli, PU Wenjing, et al |
Yuxi Hospital of Traditional Chinese Medicine, Yunnan Yuxi 653100, China |
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Abstract Objective: To investigate the effect of Yiyaobi Ⅱ on the expression and biological behavior of mouse model of rheumatoid arthritis by mediating KLF2 regulation of PI3K/Akt/mTOR pathway. Methods: A total of 80 Kunming mice were divided into control group, model group, Yiyaobi Ⅱ group, low dose group and high dose group. Except the control group, RA model was established by intradermal injection of Freund's complete adjuvant in the left posterior toe of the other groups. Yiyaobi Ⅱ group, low, and high dose groups were given corresponding doses of drugs by intragastric administration on the first day of successful modeling for 3 months, and control group and model group were given equal volume of normal saline. After the experiment, PEL, joint inflammation score and toe volume were measured. The levels of KLF2, PI3K, Akt and mTOR were determined by RT-PCR, Western blot and immunohistochemistry. Results: The PEL of the model group was lower than that of the control group, while the arthritis inflammation score and paw volume were higher than those of the control group (P<0.05). In the low- and high-dose Yiyaobi Ⅱ groups, the PEL was higher, and the arthritis inflammation score and paw volume were lower compared to the model group (P<0.05). With increasing doses of Yiyaobi Ⅱ, PEL increased, while the arthritis inflammation score and paw volume decreased (P<0.05). The expression of KLF2, PI3K, Akt, and mTOR mRNA and proteins in the ankle cartilage of the model group was higher than in the control group (P<0.05). In the low- and high-dose Yiyaobi Ⅱ groups, the expression of these markers was lower than in the model group (P<0.05), with expression levels decreasing as the dose increased (P<0.05).Conclusion:Yiyaobi Ⅱ has a significant therapeutic effect on rheumatoid arthritis in mice, notably inhibiting synovitis and inflammation in the ankle cartilage. The mechanism is associated with suppressing the activation of the KLF2-PI3K-Akt-mTOR pathway in rheumatoid arthritis.
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