Regulation of Yukouling on Inflammatory Cytokines in Rats with RAU Based on Toll Receptor and PI3K/AKT/mTOR Signal Pathway

doi:10.13701/j.cnki.kqyxyj.2023.01.013

Abstract

Abstract: Objective: To investigate the healing-promoting effect of yukouning on mucosal wounds and its effect on TLR4/PI3K/Akt/mTOR and related pathways in rats with RAU. Methods: Forty SPF-grade SD rats were divided into four groups randomly: blank control group, model control group, levamisole group, and yukouning group, with 10 rats in each group. Excluding the blank control group, the remaining three groups of rats were established by chemical cautery method for RAU modeling and the drugs were administered continuously for 7 days. The size and healing of oral ulcer surface of the rats were compared at day 0, 1, 3, and 7 after modeling administration. The rats were executed after 7 days of administration. The histopathological changes of oral mucosa of rats were observed by hematoxylin-eosin (HE) staining. Western blot was used to detect the expression of TOLL-like receptor4 (TLR4), phosphatidylinositol-3-kinase (PI3K), phosphorylated phosphatidylinositol-3-kinase (p-PI3K), protein kinase B (Akt), nuclear factor-κB (NF-κB), and mammalian target of rapamycin (mTOR) protein in the ulcerated tissues. The levels of tumor necrosis factor (TNF-α) and serum interleukin-6 (IL-6) inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Results: Except the blank control group, the other three groups all developed oral ulcers. After treatment, the ulcer surface of yukouning group and levamisole group healed well, while the ulcer scar was seen in the model group. In serum of model group, IL-6 and TNF-α were significant increased in concentration. Among them, TLR4, Akt, NF-κB, and mTOR were upregulated, and p-PI3K/PI3K was remarkable down-regulated (P<0.01). The contents of IL-6 and TNF-α in the yukouning and levamisole groups were significantly decreased compared with that of model control group (P<0.01), in which the expressions of TLR4, Akt, NF-κB, and mTOR were significantly downregulated (P<0.01) and p-PI3K/PI3K were significantly upregulated (P<0.01). Conclusion: Yukouning can help heal of oral ulcers in rats and reduce the level of inflammatory factors and improve oral mucosal damage and inflammation by inhibiting the activity of TLR4/PI3K/Akt/mTOR pathway.

Key words: yukouning, recurrent aphthous ulcer, TOLL receptor, PI3K/Akt pathway, inflammatory factors

LIU Jiawen, WANG Hanming, YANG Xianghui, FAN Zhilong, HE Xiaoming, GAN Yujuan, LIU Hejing. Regulation of Yukouling on Inflammatory Cytokines in Rats with RAU Based on Toll Receptor and PI3K/AKT/mTOR Signal Pathway[J]. Journal of Oral Science Research, 2023, 39(1): 68-73.

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