Immunomodulatory effects of a multi-component pharmacological intervention on diabetic peripheral neuropathy in type 2 diabetic rats: An exploratory study.

Abstract

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) and is closely linked to immune and inflammatory dysregulation. Multi-component pharmacological interventions have been explored as complementary approaches for metabolic and immune modulation; however, their effects on DPN and related mechanisms remain incompletely understood. A rat model of T2DM-associated peripheral neuropathy was established, and a multi-component pharmacological intervention (MPCI) was administered for 8 weeks. Peripheral nerve dysfunction was evaluated by motor and sensory nerve conduction velocities (MNCV and SNCV), behavioral outcomes, and histological/ultrastructural assessments. In parallel, spleen tissues were collected for transcriptomic profiling. RNA sequencing was performed to identify differentially expressed genes and immune-related pathways, and representative molecules involved in inflammatory regulation were further validated using western blotting and quantitative real-time PCR in sciatic nerve tissue. MPCI administration significantly ameliorated peripheral nerve dysfunction in T2DM rats, as evidenced by improved nerve conduction velocities and pathological features. Transcriptomic analysis of spleen tissue revealed that MPCI was associated with broad remodeling of diabetes-related immune and inflammatory gene programs. In parallel, sciatic nerve analyses showed attenuation of NF-κB/c-Jun-associated inflammatory signaling and modulation of inhibitory regulators at both the protein and mRNA levels. These findings indicate that MPCI improves T2DM-associated DPN and is associated with splenic immune remodeling and attenuation of peripheral nerve inflammatory signaling, providing exploratory evidence for associations between splenic immune transcriptomic remodeling and peripheral nerve inflammatory signaling.