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.
程祎睿, 王艺灿, 刘墨熙萱, 张浩锋, 刘紫薇,郭榆西, 贾雪梅, 杜姚, 杨倩. 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[J]. 河北医学, 2025, 31(1): 1-8.
CHENG Yirui, WANG Yican, LIU Moxixuan, et al. Mechanism of Huazhuo Jiedu Decoction in the Treatment of Ulcerative Colitis Based on p38MAPK Signaling Pathway. HeBei Med, 2025, 31(1): 1-8.
[1] Yadav RK,Minz E,Mehan S.Understanding abnormal c-JNK/p38MAPK signaling in amyotrophic lateral sclerosis:potential drug targets and influences on neurological disorders[J].CNS Neurol Disord Drug Targets,2021,20(5):417-429. [2] Patra R,Dey AK,Mukherjee S.Identification of genes critical for inducing ulcerative colitis and exploring their tumorigenic potential in human colorectal carcinoma[J].PLoS One,2023,18(8):289064. [3] Du L,Ha C.Epidemiology and pathogenesis of ulcerative colitis[J].Gastroenterol Clin North Am,2020,49(4):643-654. [4] Wang CJ,Ko GR,Lee YY,et al.Polymeric DNase-I nanozymes targeting neutrophil extracellular traps for the treatment of bowel inflammation[J].Nano Converg,2024,11(1):6. [5] Riviere P,Li Wai Suen C,Chaparro M,et al.Acute severe ulcerative colitis management:unanswered questions and latest insights[J].Lancet Gastroenterol Hepatol,2024,9(3):251-262. [6] 安玉秋,王惠娟.溃疡性结肠炎中医证型分布及与肠镜象相关性研究进展[J].中国中西医结合消化杂志,2021,29(5):373-376. [7] 李佃贵.从浊毒理论的建立与应用谈中医学创新与发展[J].中医杂志,2020,61(22):1938-1940. [8] Zhang YY,Wang H,Wang SL,et al.Mechanism of traditional Chinese medicine in treating ulcerative colitis-related colorectal cancer by regulating NF-κB-related signaling pathways:a review[J].Zhongguo Zhong Yao Za Zhi,2024,49(6):1455-1466. [9] Huang J,Wu T,Zhong Y,et al.Effect of curcumin on regulatory B cells in chronic colitis mice involving TLR/MyD88 signaling pathway[J].Phytother Res,2023,37(2):731-742. [10] 王倬,陈强,孔斌等.葛根芩连裁减方结合益生菌对溃疡性结肠炎血清IL-6、IL-12、IL-10和TGF-β水平的影响[J].中华中医药学刊,2022,40(3):248-251. [11] Wang R,Li XQ,Wang MR,et al.Effect ofKangfuxiaomi suppository on pelvic inflammatory disease in rats[J] ReprodImmunol,2023,16(10):104-114. [12] 毛文浩,黄丽萍,马望等.构建表达IL-2的大肠埃希菌对小鼠肠炎的影响[J].中国微生态学杂志,2020,32(10):1123-1127,1133.