基于p38MAPK信号通路探讨化浊解毒方治疗溃疡性结肠炎的作用机制

doi:10.3969/j.issn.1006-6233.2025.01.001

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Abstract Objective: To investigate the mechanism of Huazhuo jiedu decoction in the treatment of ulcerative colitis (UC). Methods: Sixty SPF C57BL/6 mice were randomly assigned to six groups: a blank group (N), a model group (M), a mesalazine group (MS), and three groups receiving different doses of Huazhuo Jiedu formula (HZJD-H, HZJD-M, and HZJD-L). Except for the N group, the UC mouse model was induced using a 2.5% DSS solution. After 7 days, the mice exhibited mucus, pus, and bloody stools. Two mice from the M group were randomly selected and sacrificed, and their colon specimens were examined under a microscope to assess pathological changes such as congestion, edema, and ulceration. Two mice died during the modeling process, one each from the MS group and the HZJD-L group. The N group was fed normally, the MS group received a mesalazine suspension at 0.52g·kg^-1·d^-1 by gavage, and the HZJD-L, HZJD-M, and HZJD-H groups received Huazhuo jiedu decoction suspensions at 12.5, 25, and 50g·kg^-1·d^-1, respectively, by gavage. The M group received 0.9% saline by gavage, administered once daily for 14 consecutive days. After the mice were sacrificed, histopathological examination of intestinal mucosal tissue was performed, and histopathological scores (HS) were assigned. The ultrastructure of colon mucosal tissue was observed using transmission electron microscopy. The protein expressions of MKK6, p38MAPK, and p-p38MAPK in colon tissue from each group were detected using Western blot, p38MAPK expression in colon tissue was assessed by immunohistochemistry, and the levels of IL-12 and IL-2 in serum from each group were measured by enzyme-linked immunosorbent assay (ELISA). Results: Hematoxylin-eosin (HE) staining showed that the pathological changes in the colon mucosa of UC mice in each treatment group were ameliorated. Transmission electron microscopy revealed that the ultrastructure of the colon mucosa in each treatment group was repaired to varying degrees. Statistical analysis indicated that, compared with the N group, the HS score, MKK6, p38, and p-p38/p38 protein expressions in colon tissue, and serum IL-12 levels were increased, while serum IL-2 levels were decreased in the M group (P<0.05). Compared with the M group, the HS score, MKK6, p38, and p-p38/p38 protein expressions in colon tissue, and serum IL-12 levels were decreased, while serum IL-2 levels were increased in each treatment group (P<0.05). Conclusion: Huazhuo jiedu decoction can improve the general condition, histopathological state, and cellular ultrastructure of UC mice, potentially by inhibiting the activation of the p38MAPK signaling pathway.

Key words： Ulcerative colitis p38MAPK Huazhuo jiedu decoction

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.01.001 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I1/1

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