电针调控TXNIP/NLRP3通路介导的焦亡途径对新生大鼠缺氧缺血性脑损伤的保护作用研究

doi:10.3969/j.issn.1006-6233.2021.08.01

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Abstract Objective: To explore the protective effect and mechanism of electroacupuncture on neonatal hypoxic ischemic brain damage (HIBD) rats. Methods: Neonatal SD rats were randomly divided into sham operation group, HIBD group, electroacupuncture group, electroacupuncture + TXNIP NC group and electroacupuncture + TXNIP OE group, HIBD model was established by modified RICE method in all but the sham groups. Rats in electroacupuncture group, electroacupuncture + TXNIP NC group and electroacupuncture + TXNIP OE group were treated with electroacupuncture. Rats in electroacupuncture + TXNIP NC group and electroacupuncture + TXNIP OE group were injected with TXNIP NC CRISPR plasmid and TXNIP OE CRISPR plasmid solution via cerebral ventricle respectively. Rats in electroacupuncture group were injected with sterile normal saline. At the end of the treatment cycle, Morris water maze was used to test the abilities of learning and memory; triphenyltetrazolium chloride (TTC) was used to measure the volume of cerebral infarction, Nissl and hematoxylin-eosin (HE) staining were used to observe the morphology of hippocampal neurons; immunofluorescence was used to detect the pyroptosis of hippocampal cells; western blot was used to detected the expressions of cleaved cysteinyl aspartate specific proteinase-1(cleaved caspase-1), pro-cysteinyl aspartate specific proteinase-1(pro-caspase-1), apotosis-associated speck-like protein (ASC), thioredoxin interacting protein (TXNIP) and Nod-like receptor protein 3 (NLRP3) in rat hippocampus; enzyme linked immunosorbent assay was used to detect the expression of interleukin (IL)-18 and IL-1β in rat hippocampus. Results: There was no cerebral infarction in the control group, and the arrangement of neurons in hippocampus was regular and dense. Compared with sham group, HIBD group had disordered and loose arrangement of nerve cells in hippocampus, cerebral infarction volume, escape latency, cleaved-caspase-1+TUNEL+ cells in hippocampus, cleaved-caspase-1/pro-caspase-1, ASC, TXNIP, NLRP3 protein, IL-18, IL-1 β levels were significantly increased, and times of crossing platform were significantly decreased (P<0.05). Compared with HIBD group, the injury of hippocampal cells in electroacupuncture group and electroacupuncture+TXNIP NC group was significantly improved, cerebral infarction volume, escape latency, cleaved-caspase-1+TUNEL+ cells in hippocampus, cleaved-caspase-1/pro-caspase-1, ASC, TXNIP, NLRP3 protein, IL-18, IL-1 β levels were decreased, and times of crossing platform were increased (P<0.05). Compared with electroacupuncture group and electroacupuncture+TXNIP NC group, electroacupuncture+TXNIP OE group had more cell damage in hippocampus, cerebral infarction volume, escape latency, cleaved-caspase-1+TUNEL+ cells in hippocampus, cleaved-caspase-1/pro-caspase-1, ASC, TXNIP, NLRP3 protein, IL-18, IL-1 β levels were increased, and times of crossing platform were decreased (P<0.05). Conclusion: In the HIBD model of rats, electroacupuncture may reduce the damage of nerve cells and improve the learning and memory abilities by inhibiting the pyroptosis mediated by TXNIP/NLRP3 pathway.

Key words： Neonatal hypoxic ischemic brain damage Electroacupuncture Thioredoxin interacting protein/Nod-like receptor protein 3 pathway Pyroptosis

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2021.08.01 OR http://www.hbyxzzs.cn/EN/Y2021/V27/I8/1233

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