金丝桃苷调节TXNIP/NLRP3信号通路对细菌性脑膜炎大鼠神经炎症的影响

doi:10.3969/j.issn.1006-6233.2024.08.06

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Abstract Objective: To analyze the effects of Hypericin (Hyp) on neuroinflammation in bacterial meningitis (BM) rats by regulating the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway.Methods: Fifteen healthy rats were randomly selected as the control group (tail vein injection of saline). BM model rats were randomly divided into BM group (tail vein injection of saline), L-Hyp group (tail vein injection of 10mg/kg Hyp), H-Hyp group (tail vein injection of 50mg/kg Hyp), TXNIP-AAV group (tail vein injection of TXNIP-AAV), AAV group (tail vein injection of AAV-NC), and Resveratrol (Res) group (tail vein injection of 30mg/kg Res). Neurological function after treatment was evaluated using the Loeffler score; white blood cell (WBC) count was determined using a blood cell analyzer; reactive oxygen species (ROS), interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in cerebrospinal fluid (CSF) were analyzed by ELISA; brain tissue water content was measured; pathological changes in brain tissue were observed using HE staining; cell apoptosis in brain tissue was observed using TUNEL staining; and protein expressions of TXNIP, NLRP3, caspase-1, apoptosis-associated speck-like protein (ASC), ionized calcium-binding adaptor molecule 1 (Iba1), and IL-1β in brain tissue were analyzed using Western blotting.Results: Compared with the control group, the BM group showed increased levels of ROS, WBC, IL-1β, IL-6, and TNF-α in CSF, increased brain tissue water content and cell apoptosis rate, and decreased Loeffler scores (P<0.05). Compared with the BM group, the L-Hyp and H-Hyp groups showed increased Loeffler scores, and decreased levels of ROS, WBC, IL-1β, IL-6, and TNF-α in CSF, brain tissue water content, and cell apoptosis rate (P<0.05). Compared with the H-Hyp group, the TXNIP-AAV and AAV groups showed increased levels of ROS, WBC, IL-1β, IL-6, and TNF-α in CSF, brain tissue water content, and cell apoptosis rate, and decreased Loeffler scores (P<0.05), whereas the Res group showed increased Loeffler scores and decreased levels of ROS, WBC, IL-1β, IL-6, and TNF-α in CSF, brain tissue water content, and cell apoptosis rate (P<0.05). The brain tissues of rats in the control group showed normal morphology; in the BM, TXNIP-AAV, and AAV groups, brain tissues showed morphological changes, disordered cell arrangement, and nuclear shrinkage; in the L-Hyp, H-Hyp, and Res groups, brain tissues showed improved morphology, with reduced cell necrosis and shrinkage. Compared with the control group, the BM group showed increased expressions of TXNIP, NLRP3, caspase-1, ASC, Iba1, and IL-1β in brain tissues (P<0.05). Compared with the BM group, the L-Hyp and H-Hyp groups showed decreased expressions of TXNIP, NLRP3, caspase-1, ASC, Iba1, and IL-1β in brain tissues (P<0.05). Compared with the H-Hyp group, the TXNIP-AAV and AAV groups showed increased expressions of TXNIP, NLRP3, caspase-1, ASC, Iba1, and IL-1β in brain tissues, while the Res group showed decreased expressions of these proteins (P<0.05).Conclusion: Hypericin may inhibit neuroinflammation in BM rats, possibly through inhibition of the TXNIP/NLRP3 pathway.

Key words： Hypericin Thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor protein 3 pathway Bacterial meningitis Neuroinflammation

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.08.06 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I8/1261

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