【摘要】 【目的】评价气滞胃痛颗粒对小鼠抑郁合并肠易激综合征的治疗作用。【方法】将48只SPF级雄性C57BL/6J小鼠随机分为正常组，模型组，氟西汀组和气滞胃痛颗粒低、中、高剂量组，每组8只。适应性喂养后，除正常组，其他各组小鼠建立慢性社交挫败应激（CSDS）模型。造模成功后，分组治疗。治疗后，通过行为学观察小鼠抑郁样行为，采用腹壁撤退反射实验、胃肠推进实验评价肠动力及肠道敏感性的变化，采用Western Blot和实时荧光定量聚合酶链式反应（RT-qPCR）法检测结肠紧密连接蛋白5(Claudin-5)及相关基因（Cldn1、Ocln、Tjp1）与核心靶点的表达，采用苏木精-伊红（HE）染色法观察结肠病理变化，利用网络药理学筛选气滞胃痛颗粒活性成分及作用靶点，并通过分子对接验证结合活性。【结果】气滞胃痛颗粒组小鼠抑郁样行为得到了显著改善，并且缓解了抑郁诱发的肠道不适。抑郁样行为小鼠结肠段肠道屏障蛋白Claudin-5及基因（Cldn1、Ocln、Tjp1）表达显著降低（P<0.01），给药后有所回调（P<0.05）。网络药理学筛选出气滞胃痛颗粒85个活性成分，其与肠易激综合征和抑郁症的疾病靶点有50个共同靶点，核心靶点包括IL-6、AKT1、TNF、PTGS2等，富集通路涉及TNF、IL-17等炎症信号通路；分子对接结果提示，胀果香豆素甲与AKT1结合能最低（-11.4 kcal/mol）。Western Blot实验结果表明抑郁样行为小鼠结肠段p-AKT与IL-6的蛋白表达水平均显著升高，给药后显著回调（P<0.01）。【结论】气滞胃痛颗粒以“多成分-多靶点-多通路”的调控模式，可能通过其核心成分作用于AKT1等关键靶点，抑制其磷酸化及下游IL-6等炎症因子的释放，从而改善抑郁样行为并修复肠道屏障功能。该结果为气滞胃痛颗粒的“老药新用”提供了新参考。更多还原

【Abstract】 Objective To evaluate the therapeutic effects of Qizhi Weitong Granules on mice with depression complicated by irritable bowel syndrome. Methods Forty-eight SPF-grade male C57 BL/6J mice were randomly divided into a normal group,a model group,a fluoxetine group,and low-,medium-,and high-dose Qizhi Weitong Granules groups, with 8 mice in each group. After adaptive feeding, a chronic social defeat stress(CSDS) model was established in all groups except the normal group. Following successful modeling,the groups received respective treatments. After treatment, depressive-like behaviors in mice were observed through behavioral tests,and changes in intestinal motility and sensitivity were evaluated using the abdominal withdrawal reflex and gastrointestinal propulsion tests. Western Blot and real-time quantitative polymerase chain reaction(RTqPCR) were used to detect the expression of colonic tight junction protein 5(Claudin-5) and relative genes,Cldn1, Ocln, Tjp1) and core targets. Hematoxylin-eosin(HE) staining was employed to observe colonic pathological changes. Network pharmacology was utilized to screen the active components and action targets of Qizhi Weitong Granules,and molecular docking was performed to validate binding activities. Results Depressive-like behaviors in mice from the Qizhi Weitong Granules groups were significantly improved, and the depressioninduced intestinal discomfort was alleviated. In mice exhibiting depressive-like behaviors,the expression of the colonic intestinal barrier protein Claudin-5 and the genes(Cldn1,Ocln,Tjp1) was significantly decreased(P<0.01),and these levels were restored to varying degrees after drug administration(P<0.05). Network pharmacology screening identified 85 active components and 50 common targets. Core targets included IL-6, AKT1, TNF,PTGS2, etc., with enriched pathways involving inflammatory signaling pathways such as TNF and IL-17. Molecular docking suggested that Inermin exhibited the lowest binding energy with AKT1(-11.4 kcal/mol). Western Blot results demonstrated that the protein expression levels of p-AKT and IL-6 in the colonic segment of mice with depressive-like behaviors were significantly elevated, which were notably restored after drug administration(P<0.01). Conclusion Qizhi Weitong Granules in a “multi-component, multi-target, multipathway” regulatory pattern through core components may act on key targets such as AKT1, inhibiting its phosphorylation and the subsequent release of inflammatory factors like IL-6, thereby ameliorating depressivelike behaviors and repairing intestinal barrier function. This study provides a new reference for the “new use of an established drug” for Qizhi Weitong Granules.更多还原