基于PI3K/Akt/NF-κB通路探讨增味承气合剂治疗大鼠肠梗阻的药效及作用机制*

作者:龚 颖1,董 越1,刘雨晨1,张金辉1,宣自华1,李 青3,张春彬3,谢冬梅1,2

单位:1.安徽中医药大学药学院,安徽 合肥 230012; 2.安徽省中医药科学院中药资源开发与利用研究所,安徽 合肥 230012; 3.滁州市中西医结合医院,安徽 滁州 239000

引用:引用:龚颖,董越,刘雨晨,张金辉,宣自华,李青,张春彬,谢冬梅.基于PI3K/Akt/NF-κB通路探讨增味承气合剂对治疗大鼠肠梗阻的药效及作用机制[J].中医药导报,2025,31(10):34-40.

DOI:10.13862/j.cn43-1446/r.2025.10.006

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摘要:

目的:探讨增味承气合剂对粘连性肠梗阻大鼠的药效作用并探究作用机制。方法:50SD大鼠随机分为空白对照组7只、假手术组11只及造模组32只。造模组大鼠采用半结扎法建立大鼠肠梗阻模型,除损耗外造模成功的大鼠随机分为模型组9只、大承气汤组8只和增味承气合剂组8只。大承气汤组和增味承气合剂组灌胃并在1 h后灌肠给予相应药物(1 mL/100 g),空白对照组、假手术组和模型组灌胃并在1 h后灌肠给予0.9%氯化钠注射液(1 mL/100 g),2/d,共治疗11次,观察各组大鼠进食量;酶联免疫吸附测定(ELISA)检测各组大鼠血清中白细胞介素-1β(IL-1β)、白细胞介素-6IL-6)、肿瘤坏死因子-α(TNF-α)水平;苏木素-伊红(HE)染色观察回肠组织病理变化;实时荧光定量多聚核苷酸链式反应(QRT-PCR)检测回肠组织磷脂酰肌醇3-激酶(PI3KmRNA、蛋白激酶BAktmRNA、核因子κBNF-κBmRNA表达水平;蛋白质印迹法(WB)检测PI3KAktp-AktNF-κB蛋白表达水平。结果:模型组与假手术组比较,大鼠进食量降低,回肠组织发生炎性病变,血清炎症因子水平、回肠组织PI3KAktp-AktNF-κB蛋白表达水平及PI3K mRNAAkt mRNANF-κB mRNA表达水平显著升高(P0.05);在治疗治疗5 d后,大承气汤组和增味承气合剂组与模型组比较进食量、回肠组织病理变化均得到改善,血清炎症因子水平、回肠组织PI3Kp-AktNF-κB蛋白表达水平及Akt mRNANF-κB mRNA表达水平显著降低(P0.05),Akt蛋白和PI3K mRNA表达水平呈下降趋势,增味承气合剂组与大承气汤组各指标比较多无显著性差异,部分指标显著低于大承气汤组(P0.05)。结论:增味承气合剂能显著改善手术肠梗阻的表现,具有治疗肠梗阻的作用,可能通过调节PI3K/Akt/NF-κB信号通路改善大鼠体内炎性环境达到治疗作用。

关键词:粘连性肠梗阻;增味承气合剂;药效学评价;作用机制;PI3K/Akt/NF-κB信号通路;大鼠

Abstract:

Objective: To explore the pharmacological effect of Zengwei Chengqi mixture on adhesive intestinal obstruction rats and investigate its mechanism of action. Methods: Totally 50 Sprague-Dawley (SD) rats were randomly divided into blank control group (n=7), sham surgery group (n=11) and modeling group (n=32). The rats in modeling group were used to establish an intestinal obstruction model via the semi-ligation method. Excluding those dead during the modeling process, the successfully modeled rats were randomly assigned to model group (n=9), Dachengqi decoction (大承气汤) group (n=8), and Zengwei Chengqi mixture group (n=8). Rats in the Dachengqi decoction group and Zengwei Chengqi mixture group received intragastric administration of the corresponding drugs, followed by enema administration of the same drugs at a dose of 1 mL/100 g 1 hour later. Rats in the blank control group, sham surgery group and model group were given 0.9% sodium chloride injection instead, with the same administration route (intragastric first, then enema 1 hour later) and dose (1 mL/100 g). The treatment was administered twice a day for a total of 11 times, and the food intake of rats in each group was observed throughout the period. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum of rats in each group. Hematoxylin eosin (HE) staining was used to observe the pathological changes in ileal tissue. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression levels of PI3K mRNA, Akt mRNA and NF-κB mRNA in ileal tissue. Western blotting (WB) was used to detect the expression levels of PI3K, Akt, p-Akt and NF-κB proteins. Results: Compared with the sham surgery group, the model group showed a decrease in food intake and inflammatory lesions in the ileum tissue. The levels of serum inflammatory factors, protein expression of PI3K, Akt, p-Akt and NF-κB, and expression of PI3K mRNA, Akt mRNA and NF-κB mRNA in the ileum tissue were significantly increased in model group (P0.05). After 5 days of intervention treatment, the food intake and pathological changes in the ileum tissue of Dachengqi decoction group and Zengwei Chengqi mixture group were improved compared with the model group. The levels of serum inflammatory factors, protein expression of PI3K, p-Akt and NF-κB, and expression of Akt mRNA and NF-κB mRNA expression in the ileum tissue were significantly reduced in Dachengqi decoction group and Zengwei Chengqi mixture group (P0.05). The expression levels of Akt protein and PI3K mRNA showed a downward trend. There were no significant differences in various indicators between the Zengwei Chengqi mixture group and Dachengqi decoction group, while some indicators were significantly lower than those in the Dachengqi decoction group (P0.05). Conclusion: Zengwei Chengqi mixture group can significantly improve the symptoms of surgical intestinal obstruction and has a therapeutic effect on intestinal obstruction. It may improve the inflammatory environment in rats by regulating the PI3K/Akt/NF-κB signaling pathway.

Key words:adhesive intestinal obstruction; Zengwei Chengqi mixture; pharmacodynamic evaluation; mechanism; PI3K/Akt/NF-κB signaling pathway; rat

发布时间:2026-01-08

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