基于PI3K-AKT信号通路探讨疏肝运脾汤对结直肠癌伴抑郁障碍患者抑郁焦虑症状的调节作用

Regulatory effect of Shugan Yunpi Decoction on depressive and anxiety symptoms in colorectal cancer patients with depressive disorder based on the PI3K-AKT signaling pathway

中文关键词:  结直肠癌  抑郁障碍  疏肝运脾汤  PI3K-AKT信号通路

英文关键词:Colorectal cancer  Depressive disorder  Shugan Yunpi Decoction  PI3K-AKT signaling pathway

中文摘要:

      背景 结直肠癌患者常共病抑郁障碍，严重影响其生活质量和治疗依从性，并削弱肿瘤治疗效果与预后。现有治疗方法存在局限，尤其在肿瘤治疗与抑郁治疗的协同干预方面缺乏系统性和针对性。探索安全有效的综合干预新方案，并明确其深层作用机制，具有重要的临床意义。目的 基于PI3K-AKT信号通路，探索疏肝运脾汤改善结直肠癌伴抑郁障碍患者抑郁和焦虑症状的效果和安全性，以期为结直肠癌伴抑郁障碍的综合治疗提供参考。方法 本研究为随机对照试验。纳入2023年11月—2025年7月保定市第一中医院收治的、符合《中国结直肠癌诊疗规范（2023版）》结直肠癌诊断标准及《中国精神障碍分类与诊断标准（第3版）》（CCMD-3）抑郁障碍诊断标准的106例患者为研究对象。采用随机数字表法分为研究组和对照组各53例。对照组接受常规化疗联合中医五行音乐治疗，研究组接受常规化疗联合疏肝运脾汤治疗，两组均治疗8周。采用汉密尔顿抑郁量表17项版（HAMD-17）和汉密尔顿焦虑量表（HAMA）分别评定抑郁和焦虑症状。采用Western blot蛋白免疫印迹法检测PI3K、AKT、pAKT蛋白表达水平；采用实时荧光定量逆转录聚合酶链反应（qRT-PCR）检测PI3K mRNA、AKT mRNA表达水平。采用自制不良反应记录表记录不良反应发生情况。结果 重复测量方差分析结果显示，两组HAMD-17和HAMA评分的时间效应（F=139.336、234.747）、组别效应（F=43.900、101.266）以及时间与组别的交互效应（F=13.409、43.216）均有统计学意义（P均<0.01）。治疗4周和8周后，两组HAMD-17和HAMA评分均低于治疗前，差异均有统计学意义（P均<0.05）；治疗4周和8周后，研究组HAMD-17和HAMA评分均低于对照组（P均<0.01）。两组PI3K、AKT、pAKT蛋白表达水平的时间效应（F=571.356、309.266、414.492）、组别效应（F=6.901、26.361、39.362）以及时间与组别的交互效应（F=18.592、19.266、33.484）均有统计学意义（P均<0.01）。治疗8周后，研究组PI3K、pAKT蛋白表达水平均低于对照组，AKT蛋白表达水平高于对照组（P均<0.01）。两组PI3K mRNA、AKT mRNA表达水平的时间效应（F=338.555、225.059）、组别效应（F=5.429、9.726）以及时间与组别的交互效应（F=12.953、21.214）均有统计学意义（P均<0.01）。治疗8周后，研究组PI3K mRNA、AKT mRNA表达水平均低于对照组（P均<0.05）。研究组不良反应发生率低于对照组（χ²=4.810，P<0.05）。结论 疏肝运脾汤可能通过调控PI3K-AKT信号通路，改善结直肠癌伴抑郁障碍患者的抑郁和焦虑症状，降低PI3K、pAKT、PI3K mRNA、AKT mRNA表达水平，且安全性较好。

英文摘要:

      Background Patients with colorectal cancer are frequently comorbid with depression， which severely affects the quality of life and treatment compliance， while compromising the efficacy of anticancer treament and prognosis. Current therapeutic strategies still have notable limitations， particularly the lack of systematic and targeted synergistic regimens that integrate oncological management and anti-depressive intervention. It is of great clinical significance to explore a safe and effective new comprehensive intervention protocol and clarify its underlying mechanism of action.Objective To explore the effectiveness and safety of Shugan Yunpi Decoction in alleviating depressive and anxiety symptoms in colorectal cancer patients with depressive disorder through the PI3K-AKT signaling pathway， in order to provide references for the comprehensive treatment of colorectal cancer and depressive disorder.Methods This study was a randomized controlled trial. A total of 106 patients admitted to the Baoding No.1 Hospital of traditional Chinese medicine from November 2023 to July 2025 were enrolled， who met the diagnostic criteria for the Chinese protocol of diagnosis and treatment of colorectal cancer （2023 edition） and the diagnostic criteria for depressive disorder as specified in the Chinese Classification and Diagnostic Criteria of Mental Disease， third edition （CCMD-3）. Patients were divided into the study group and the control group using a random number table， with 53 cases in each group. The control group received conventional chemotherapy combined with traditional Chinese medicine five-element music therapy， while the study group received conventional chemotherapy combined with Shugan Yunpi Decoction therapy. Both groups were treated for 8 weeks. Depressive and anxiety symptoms were assessed using the Hamilton Depression Scale-17 item（HAMD-17） and Hamilton Anxiety Scale （HAMA）， respectively. Western blot protein immunoblotting was used to detect the expression levels of PI3K， AKT， and pAKT. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （qRT-PCR） was used to detect the expression levels of PI3K mRNA and AKT mRNA. Adverse reactions were recorded using a self-designed adverse reaction record form.Results Repeated measures analysis of variance showed that the time effects （F=139.336， 234.747）， group effects （F=43.900， 101.266）， and time-group interaction effects （F=13.409， 43.216） for HAMD-17 and HAMA scores in both groups were statistically significant （P<0.01）. After 4 and 8 weeks of treatment， the HAMD-17 and HAMA scores in both groups were lower than those before treatment， with statistically significant differences （P<0.05）. HAMD-17 and HAMA scores in the study group were lower than those in the control group （P<0.05）. The time effects （F=571.356， 309.266， 414.492）， group effects （F=6.901， 26.361， 39.362）， and time-group interaction effects （F=18.592， 19.266， 33.484） for the protein expression levels of PI3K， AKT， and pAKT in both groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the protein expression levels of PI3K and pAKT in the study group were lower than those in the control group， while the AKT protein expression level was higher than that in the control group（P<0.01）. The time effects （F=338.555， 225.059）， group effects （F=5.429， 9.726）， and time-group interaction effects （F=12.953， 21.214） for PI3K mRNA and AKT mRNA expression levels in two groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the expression levels of PI3K mRNA and AKT mRNA in the study group were lower than those in the control group （P<0.05）. The incidence of adverse reactions in the study group was lower than that in the control group （χ²=4.810， P<0.05）.Conclusion Shugan Yunpi Decoction may help to ameliorate depressive and anxiety symptoms in colorectal cancer patients with depressive disorder by regulating the PI3K-AKT signaling pathway， decreasing the levels of PI3K， pAKT， PI3K mRNA， and AKT mRNA， with a favorable safety profile. ［Funded by Baoding City Science and Technology Planning Project （number， 2341ZF291）］