| Abstract:Objective To investigate the effect of Triptolide on cerebral ischemia- reperfusion injury (CIRI) and explore its molecular mechanism. Methods One hundred and forty-four Wistar rats were randomly divided into sham operation group, model group, low, medium and high dose of triptolide group and butylphthalide group, with 24 rats in each group. The CIRI rat model was established by blocking the middle cerebral artery for 2 hours. 3 days before modeling, the rats in each group were ip administration once a day. 24 hours after reperfusion, the neurological deficit score was detected, the rate of cerebral infarction were measured by TTC staining, the blood brain barrier (BBB) permeability was detected by EB penetration test. The pathological changes neurons in the ischemic penumbra cortex were observed by HE staining and TUNEL staining. The content of inflammatory factors in ischemic cerebral cortex were detected by ELISA method. The expression of TLR4/NF-κB pathway related proteins were detected by Western blot. Results Compared with the model group, the neurological deficit score, cerebral infarction rate and EB content in the Triptolide middle, high dose groups and the Butylphthalide group were significantly decreased (P<0.05). The pathological changes of cortical neurons in the ischemic penumbra were significantly improved, and the apoptosis rate of neurons was significantly decreased (P<0.05). The content of TNF-α, IL-1β and the expression of TLR4, p-NF-κB, cleaved Caspase-3, Bax were significantly decreased, the expression of Bcl-2 was significantly increased, the ratio of p-NF-κB/NF-κB and Bax/Bcl-2 were significantly decreased (P<0.05). The regulatory effect of the high-dose triptolide group on various detection indexes were better than that of the Butylphthalide group (P<0.05). Conclusion Triptolide can protect the permeability of BBB, improve the neurological deficit and neuropathy in CIRI rats, and reduce the rate of cerebral infarction, its mechanism may be related to the inhibition of TLR4/NF-κB pathway and which mediated inflammatory response and neuronal apoptosis. |
