高剂量阿托伐他汀作为附加治疗对重度抑郁症患者症状、血清AMPK/NLRP3炎性小体及IL-6/STAT3信号轴的影响：随机对照临床研究
Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.
作者信息
Aldossary Khlood Mohammad, Ali Lashin Saad, Abdallah Mahmoud S, Bahaa Mostafa M, Elmasry Thanaa A, Elberri Eman I, Kotkata Fedaa A, El Sabaa Ramy M, Elmorsi Yasmine M, Kamel Mostafa M, Negm Walaa A, Elberri Aya Ibrahim, Hamouda Amir O, AlRasheed Hayam Ali, Salahuddin Muhammed M, Yasser Mohamed, Hamouda Manal A
机构信息
Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman, Jordan.
出版信息
Front Pharmacol. 2024 May 24;15:1381523. doi: 10.3389/fphar.2024.1381523. eCollection 2024.
BACKGROUND
Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression.
AIM
To investigate the mechanistic pathways of high dose atorvastatin in MDD.
PATIENTS AND METHODS
This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured.
RESULTS
The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine ( = 0.03, and = 0.005), respectively.
CONCLUSION
These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3.
CLINICAL TRIAL REGISTRATION
clinicaltrials.gov, identifier NCT05792540.
背景
神经炎症通路与重度抑郁症（MDD）的发生发展有关。他汀类药物的抗炎特性已被证明在抑郁症的病理生理学中具有重要意义。
目的
研究高剂量阿托伐他汀治疗MDD的作用机制途径。
患者与方法
本试验纳入了60例符合入选标准的MDD患者。从精神科挑选患者招募两组患者（每组n = 30）。第1组患者每天服用一次20毫克氟西汀加安慰剂。第2组患者每天服用一次氟西汀和阿托伐他汀（80毫克）。所有患者均由精神科医生使用汉密尔顿抑郁量表（HDRS）进行评估。HDRS评分≤7表示缓解或部分缓解[HDRS<17且>7]。缓解定义为HDRS评分下降≥50%。测量核苷酸结合寡聚化结构域样受体蛋白3（NLRP-3）、白细胞介素-6（IL-6）、腺苷单磷酸活化蛋白激酶（AMPK）以及信号转导和转录激活因子3（STAT-3）的血清浓度。
结果
与氟西汀组相比，阿托伐他汀组所有测量指标的水平均显著降低，同时AMPK水平有统计学意义的升高。与基线水平和氟西汀组相比，阿托伐他汀组的HDRS显著降低。阿托伐他汀组的缓解率和部分缓解率分别高于氟西汀组（P = 0.03和P = 0.005）。
结论
这些结果表明，高剂量阿托伐他汀可能通过改变AMPK/NLRP3和IL-6/STAT-3信号通路，成为MDD患者一种有前景的辅助治疗方法。
临床试验注册
clinicaltrials.gov，标识符NCT05792540。
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