Matrine improves cognitive impairment and modulates the balance of Th17/Treg cytokines in a rat model of Aβ1-42-induced Alzheimer's disease

苦参碱可改善Aβ1-42诱导的阿尔茨海默病大鼠模型中的认知障碍并调节Th17/Treg细胞因子的平衡

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Abstract

Matrine (MAT) has been reported for its anti-inflammatory and neuroprotective effects. However, little is known about its effects on Th17/Treg cytokines and cognitive impairment in Alzheimer's disease (AD). In the present study, we injected Aβ 1-42 to the hippocampus of the rat to induce AD. Three groups of the AD rats were treated with MAT (25, 100 or 200 mg/kg/day, respectively) by intraperitoneal injection for 5 weeks. Levels of Th17 cell cytokines [interleukin (IL)-17A and IL-23] and regulatory T (Treg) cell cytokines [transforming growth factor β (TGF-β) and IL-35] in homogenates of the brain cortex and hippocampus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The mRNA expressions of Th17 cell specific transcription factor RORγt and Treg cell specific transcription factor Foxp3 in the brain cortex and hippocampus were quantified by real-time RT-PCR. Learning and memory ability of the rats were evaluated by Morris water maze test and novel object recognition test. ELISA detections showed the AD rats had increased levels of IL-17A and IL-23 as well as decreased levels of TGF-β and IL-35. Matrine (100 and 200 mg/kg/day) significantly reversed the alternations of Th17/Treg cytokines induced by Aβ 1-42 injection, decreased RORγt mRNA expression, increased Foxp3 mRNA expression and improved the learning and memory ability in the AD rats. The findings demonstrated that the AD rats had imbalance of Th17/Treg cytokines in the brain. MAT could dose-dependently restore the balance of Th17/Treg cytokines and attenuate the cognitive impairment in AD rats.

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