Department of Anesthesiology and Reanimation, Gaziantep City Training and Research Hospital, Gaziantep 27470, Turkey.
Department of Anesthesiology and Reanimation, Ankara Atatürk Sanatorium Training and Research Hospital, University of Health Sciences, Ankara 06000, Turkey.
Medicina (Kaunas). 2024 Nov 1;60(11):1791. doi: 10.3390/medicina60111791.
It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the treatment of cytokine storm and critical illness neuromyopathy (CINM) in a rat sepsis model. Rats were assigned into three groups, and a feces intraperitoneal-injection group (FIP) procedure was carried out on 30 rats to induce a model of sepsis for critical illness polyneuromyopathy (CINM). The study groups were as follows: Group 1: control (nonoperative and orally fed control, = 10), Group 2: FIP with 0.9% NaCl saline was given as 1 mL/kg/day by oral gavage ( = 10), and Group 3: FIP with 10 mg/kg/day of hydroxychloroquine (Plaquenil 200 mg) administered by oral gavage ( = 10). Electrophysiological recordings (EMG) were conducted six days after surgery. EMG was carried out three times on the right sciatic nerve, which was stimulated with supramaximal intensity utilizing a bipolar needle electrode at the sciatic notch. Tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), lactic acid levels, and interleukin-6 (IL-6) were evaluated. In terms of TNF-α, MDA, lactic acid levels, and IL-6, there was a statistically significant decrease in the CINM + 10 mg/kg HCQ group compared to the CINM and saline group ( < 0.0001, < 0.05, < 0.05, and < 0.05, respectively). Compound muscle action potentials (CMAPs) latency and duration were decreased in the CINM + 10 mg/kg HCQ group compared to other groups ( < 0.01 and < 0.001). However, CMAP amplitude was significantly higher in the CINM + 10 mg/kg HCQ group unlike the CINM and saline group ( < 0.001). This is the first study to demonstrate the effects of HCQ on CINM in a rat model of sepsis. The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress.
已知,在重症监护病房(ICU)住院超过一周的患者开始出现危重病和相关神经肌肉问题。本研究的目的是研究羟氯喹(HCQ)在治疗大鼠脓毒症细胞因子风暴和危重病神经肌肉病(CINM)中的作用。
将大鼠分为三组,并对 30 只大鼠进行粪便腹腔内注射(FIP)程序,以诱导危重病多发性神经病(CINM)的脓毒症模型。研究组如下:第 1 组:对照组(非手术和口服对照,n = 10),第 2 组:FIP 给予 1 毫升/千克/天的 0.9%生理盐水口服灌胃(n = 10),第 3 组:FIP 给予 10 毫克/千克/天的羟氯喹(Plaquenil 200 毫克)口服灌胃(n = 10)。手术后 6 天进行电生理学记录(EMG)。在坐骨神经上用双极针电极以最大刺激强度对右侧坐骨神经进行三次 EMG 记录。评估肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)、乳酸水平和白细胞介素-6(IL-6)。
就 TNF-α、MDA、乳酸水平和 IL-6 而言,CINM+10mg/kgHCQ 组与 CINM 和盐水组相比,均有统计学意义的降低(<0.0001、<0.05、<0.05 和<0.05)。与其他组相比,CINM+10mg/kgHCQ 组的复合肌肉动作电位(CMAPs)潜伏期和持续时间缩短(<0.01 和<0.001)。然而,CINM+10mg/kgHCQ 组的 CMAP 幅度明显高于 CINM 和盐水组(<0.001)。
这是第一项研究证明羟氯喹对脓毒症大鼠模型中 CINM 的作用。我们的研究结果表明,羟氯喹可能作为治疗脓毒症的潜在治疗药物。羟氯喹通过减少细胞因子的产生和氧化应激,可能在脓毒症相关 CINM 的发病机制中发挥重要作用。