Shengmaisan combined with Liuwei Dihuang Decoction alleviated CIH-induced glutamate excitotoxicity by IGF1/IGFR signaling pathway

Background: Chronic intermittent hypoxia (CIH) is the primary pathological feature of obstructive sleep apnea (OSA), and plays a key role in glutamate excitotoxicity-induced cognitive impairment.

Aims: This study aimed to investigate the effects of SMS-LD and explore the potential underlying mechanisms of cognitive dysfunction in CIH-induced glutamate excitotoxicity.

Methods: Mice were exposed to CIH (21 %-5 % O₂, 20 times/h, 8 h/d) for 35 days and SMS-LD was administered intragastrically (10, 20, or 30 g/kg) during CIH exposure. Cognitive levels, neuronal damage, mitochondrial damage, and glutamate excitotoxicity were measured. In addition, intracerebral ventricular injections of IGF1 siRNA (4 μL) and AG1024 (10 mM, 4 μL) were adopted to confirm the role of the IGF1/IGFR signalling pathway in SMS-LD therapy for CIH-induced glutamate excitotoxicity.

Results: In mice exposed to CIH, SMS-LD therapy ameliorated CIH-induced glutamate excitotoxic damage and mitochondrial dysfunction, increased the expression of IGF1 and IGFR (0.75-1.17 fold and 0.82-1.24 fold, respectively), activated the renin-angiotensin system (Ras)/rapidly accelerated fibrosarcoma (Raf) and phosphatidyqinositol-3 kinase (PI3K)/ protein kinase B (Akt) signalling pathways, and ameliorated cognitive impairment.

Conclusions: These results showed that SMS-LD ameliorated CIH-induced glutamate excitotoxicity by activating the IGF1/IGFR pathway.

Chronic intermittent hypoxia; Glutamate excitotoxicity; IGF1/IGFR signalling pathway; Mitochondrial dysfunction; Shengmaisan combined with Liuwei Dihuang decoction.