[Effects of total saponins from Trillium tschonoskii Maxim on vascular cognitive impairment and its mechanisms].

Abstract

Objective: To investigate neuroprotective effects of total saponins from Trillium tschonoskii Maxim (TST) on vascular cognitive impairment (VCI) rats through inflammatory body of the NOD-like body protein 3 (NLRP3) regulated by endoplasmic reticulum stress (ERS). Methods: SD rats were divided into sham-operated group (SHAM), model group (VCI, bilateral neck arterial ligation (BCCAO) method), TST intervention group (TST, 100 mg/kg), and positive group (donepezil hydrochloride, 0.45 mg/kg ), continuous administration for 4 weeks. The ability of learning and memory was evaluated by the morris water labor. The tissue pathological changes were observed by HE and NISSL staining. Western blot was used to detectendoplasmic reticulum-related proteins GRP78, IRE1, XBP1. Inflammasome-related proteins NLRP3, ASC, Caspase-1, IL-18, IL-1β. Results: Compared with the SHAM group, the escape latency of VCI group rats was prolonged significantly, and the number of times of crossing the platform and the percentage of target quadrant residence time were shortened (P＜0.01); The cells in the hippocampus of VCI rats were damaged, with obvious pyknosis, decreased number of neurons and damage of cell body structure; The endoplasmic reticulum and inflammatory corpuscle-associated proteins were increased in VCI group (P＜0.05 or P＜0.01). Compared with the VCI group, the TST group and the positive group had less time to search for the platform, and the ratio of the times of crossing the platform to the time in the target quadrant was longer (P＜0.05 or P＜0.01). There was no significant difference in the times of crossing the platform between the positive group and VCI group (P＞0.05); The cell damage, nuclear pyknosis and the number of neurons in TST and positive groups were significantly reduced; The endoplasmic reticulum associated proteins and inflammatory body associated proteins in TST group and positive group were decreased to different degrees (P＜0.05 or P＜0.01). Conclusion: TST has neuroprotective effects on VCI rats, and its mechanism may be related to the involvement of ERS in the regulation of NLRP3 inflammatory small bodies.