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Glutamine alleviates muscle paralysis induced by Bungarus multicinctus envenomation via the Agrin-MuSK signaling
Manqi Xiao1, Shaocong Hu2, Ningjing Jiang2
1Institute of Life Sciences of Guangxi Medical University, Nanning, 530021, PR China; AIDS Clinical Treatment Center of Guangxi (Nanning) and The Fourth People' Hospital of Nanning, 530021, PR China.
Abstract:
This study investigated the effect of glutamine (Gln) on paralytic symptoms in rats poisoned by Bungarus multicinctus and explored the underlying mechanism, focusing on the Agrin-MuSK signaling pathway in neuromuscular transmission recovery.An ex vivo diaphragm tension assay assessed Gln's reversal of venom-induced neuromuscular blockade. A rat poisoning model was established with Bungarus multicinctus venom (0.15 mg/kg). Rats were divided into normal, venom, and venom + Gln groups. We evaluated survival, paralysis, blood gases (PaO2, PaCO2, PaSO2), diaphragm histopathology and ultrastructure, and oxidative stress markers (SOD, MDA). RT-qPCR and Western Blot analyzed key Agrin-MuSK pathway components (mRNA: Agrin, Chrne, Chrna, LRP4, MuSK, Rapsyn; protein: Agrin, p-MuSK/MuSK, α1- subunit of nAChR, ε- subunit of nAChR). Gln significantly reversed venom-induced diaphragm tension decline ex vivo (P < 0.05). In vivo, high-dose Gln (750 mg/kg) significantly improved survival (P < 0.05), alleviated paralysis and hypoxia (increased PaSO2, PaO2; decreased PaCO2, P < 0.05), reduced diaphragm ultrastructural damage, and enhanced antioxidant capacity (increased SOD, decreased MDA, P < 0.05). Venom significantly suppressed key Agrin-MuSK pathway elements (Agrin, p-MuSK/MuSK; P < 0.01). Gln intervention significantly upregulated the expression of pathway molecules (Agrin, Chrne, LRP4, MuSK, Rapsyn mRNA and Agrin, p-MuSK/MuSK protein; P < 0.05 or P < 0.01).Gln effectively alleviates paralysis and improves survival in Bungarus multicinctus-poisoned rats. This protection is associated with improved neuromuscular junction ultrastructure, reduced oxidative stress, and activation of the Agrin-MuSK signaling pathway, promoting neuromuscular transmission recovery. The study provides experimental evidence and potential therapeutic targets for Gln in treating Bungarus multicinctuspoisoning, especially respiratory paralysis.
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