天津医药 ›› 2023, Vol. 51 ›› Issue (3): 259-262.doi: 10.11958/20221146
PAN Ting(), LI Zuoxiao(
), WAN Li
摘要: Objective To investigate the effect of taxol (PTX) on pyroptosis of experimental autoimmune encephalomyelitis (EAE) mice by inhibiting NOD-like receptor thermoprotein domain-associated protein 3 (NLRP3)/caspase-1 pathway. Methods Fifty female C57BL/6 mice were randomly divided into the normal control group, the EAE model group, the PTX low-dose, medium-dose and high-dose groups according to the random number table method, with 10 mice in each group. EAE model was established in other groups except the normal control group. PTX low-dose, medium-dose and high-dose groups were intraperitoneally injected with 1, 2 and 4 mg/kg PTX everyday, respectively, and normal control group and EAE model group were intraperitoneally injected with the same amount of normal saline for 14 consecutive days. From the day of immunization, changes of body weight, mental state, activity state and neurological dysfunction score of mice were observed and recorded regularly every day. Nissl staining and LFB staining were used to observe pathological changes. The mRNA expression levels of NLRP3 and caspase-1 in crushed tissues were detected by quantitative fluorescence PCR (qPCR). Levels of interleukin (IL) -18 and IL-1β in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Results There were no obvious symptoms in mice of the normal control group. Mice in the EAE model group and the PTX low-, medium-, and high-dose groups showed decreased body weight, decreased activity and sluggish response. Compared with the EAE model group, the latency and peak period were delayed in the PTX dose groups, the neurological dysfunction score at peak period was decreased (P<0.05). The number of Nyssome in spinal cord tissue was increased and relatively regular, demyelination and vacuolar changes were alleviated, and the mRNA expression levels of NLRP3 and caspase-1 were decreased. The higher the PTX dose, the more obvious the latency and peak delay. The number of Nyssome in spinal cord increased, the arrangement and morphology were more regular, the demyelination and vacuolation changes were lighter, the mRNA expression level of caspase-1 and the contents of IL-1β and IL-18 in peripheral blood were lower (P<0.05). Conclusion PTX may reduce the damage of pyroptosis in EAE mice by inhibiting NLRP3/caspase-1 pathway related inflammatory factors.
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