Effect of Triptolide on the M1/M2 Polarization of Microglia in Rats with Cerebral Ischemia-reperfusion
Objective:To investigate the effect of triptolide(TPL)on the M1/M2 polarization of microglia in rats with cerebral is-chemia-reperfusion(CIR).Methods:A total of 192 SD rats were divided into sham operation group,model group,butylphthalide(6 mg/kg)group and TPL low,medium,and high dose(0.2,0.4,0.8 mg/kg)groups,with 32 rats in each group.Except for the rats in sham operation group,the rats in other groups underwent CIR modeling by occluding the middle cerebral artery with a suture for 2 hours.Drug administration was initiated in all groups 3 days before modeling,once a day.After 24 hours of reperfusion,the neurological function,cerebral infarction rate,brain water content,pathological changes in the ischemic penumbra cortex were as-sessed.The levels of inflammatory factors in ischemic cerebral cortex were detected by enzyme-linked immunosorbent assay(ELISA).Immunofluorescence labeling was employed to detect the expression of M1-type marker CD86/(Ionized Calcium-binding Adapter Molecule,Iba-1),M2-type marker CD206/Iba-1 in microglia,and Western blot was conducted to assess the protein expres-sion of toll-like receptor 4(TLR4),nuclear factor-KB(NF-κB),and p-NF-κB.Results:Compared with the model group,the TPL medium and high-dose groups,as well as the butylphthalide group,showed significantly reduced neurological deficit scores,cerebral infarction rates,and brain water contents(P＜0.05);the pathological changes of cortical neurons in the ischemic penumbra were significantly improved.The levels of TNF-α,IL-1β,ICAM-1 were significantly decreased and the level of IL-10 was significantly in-creased.The positive rate of CD86/Iba-1 cells significantly decreased,and the positive rate of CD206/Iba-1 cells significantly in-creased(P＜0.05).The expressions of TLR4 and p-NF-KB in the ischemic cortex tissue were significantly down-regulated,and the p-NF-κB/NF-κB ratio significantly decreased(P＜0.05).Except for neurological deficit score,brain water content and IL-1β lev-el,the effects of high dose TPL on other indicators were better than those of Butylphthalide group(P＜0.05).Conclusion:TPL can inhibit CIR injury in rats,which may be related to promoting the polarization of microglia from M1 type to M2 type,inhibiting the activation of TLR4/NF-κB pathway and suppressing inflammatory responses.
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