1.Mechanism of Ziyu ointment in regulating the Ras/Raf/ERK signaling pathway to influence the postoperative wound healing in rats with perianal abscess
Yue CHEN ; Sanhua FENG ; Shanhu CHEN
China Pharmacy 2025;36(21):2668-2673
OBJECTIVE To explore the effects of Ziyu ointment on postoperative wound healing in rats with perianal abscess based on Ras/Raf protein kinase (Raf)/extracellular signal-regulated kinase (ERK) signaling pathway. METHODS The rats were randomly divided into control group, model group, vaseline treatment group (positive control group, 25 mg/cm2), Ziyu ointment group (25 mg/cm2), Ziyu ointment+PD98059 (ERK inhibitor) group (25 mg/cm2 Ziyu ointment+300 μg/L PD98059 solution 10 μL), with 12 rats in each group. A circular incision was made on the backs of rats in each group. Except for the control group, fecal supernatant was applied dropwise to induce the perianal abscess model. After successful modeling, corresponding drugs were applied topically to rats in administration group, once a day, for 14 consecutive days. The wound areas of the rats were measured on days 0, 7 and 14 of drug administration, and the wound healing rates were calculated. The levels of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] and growth factors [basic fibroblast growth factor (bFGF), epidermal growth factor (EGF)] in the serum of the rats were detected. The histopathological morphology of the wound tissues in the rats was also observed. Immunohistochemistry was used to detect the expressions of cluster of differentiation 34 (CD34) and vascular endothelial growth factor (VEGF) in the wound tissues of rats. Western blot was used to detect the expressions of the proteins related to the Ras/Raf/ERK signaling pathway in the wound tissues of rats. RESULTS Compared with control group, the wound healing rates on days 0, 7 and 14 of drug administration, serum levels of bFGF and EGF, the number of newly formed capillaries in the wound tissues, and the expression levels of CD34, VEGF, Ras, Raf1, ERK1 and ERK2 in the wound tissues of rats in the model group were all significantly decreased (P<0.05); however, serum levels of TNF-α and IL-6 were all significantly increased (P<0.05). The histopathological damage to the wound tissue was severe, with a thinned epidermal layer and only a small amount of granulation tissue formation. Compared with model group, the levels of the aforementioned quantitative indicators in rats from the Ziyu ointment group and vaseline group were significantly improved (P<0.05). The histopathological damage to the wound tissue was notably ameliorated, with increased epidermal thickness and the formation of a substantial number of newly formed capillaries and granulation tissue. Compared with Ziyu ointment group, the levels of most of the aforementioned quantitative indicators in rats from the Ziyu ointment+PD98059 group were significantly reversed (P<0.05), the histopathological damage to the wound tissue was markedly aggravated. CONCLUSIONS Ziyu ointment may alleviate the postoperative inflammatory response in the wound of rats with perianal abscess, promote angiogenesis and wound healing. Its mechanism of action may be related to the activation of the Ras/Raf/ERK signaling pathway.
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