HISTAMINE H4 RECEPTOR ANTAGONIST PROTECTS AGAINST NEURONAL DAMAGE BY INHIBITING THE PROLIFERATION AND RELEASE OF M1 MICROGLIA

Objective: To explore the mechanism of histamine H4 receptor antagonists on neuronal injury protection and inhibition of proliferation and release of M1 microglia. Methods: Forty SPF rats were selected to establish Parkinson's disease (PD) models by using rotenone to induce oxidative damage of dopaminergic neurons in the substantia nigra. Rats with successful modelling were randomly divided into the model group, histamine H4 receptor antagonist group, histamine H3 receptor antagonist group, and the M1 type microglia inhibitor group, with 10 rats in each group. They were administered with the corresponding drugs for three weeks. The expression of alpha-synuclein, tyrosine hydroxylase (TH), and calcium ion-binding molecule (IBA-1) in brain tissue of each group were detected by immunohistochemistry. HPLC-MS/MS was used to detect the dopamine content in the striatum. Apomorphine was used to induce the rotation behaviour of rats. Results: The level of substantia nigra TH in the injured part of the model group was significantly lower than that in the normal side (P<0.05). The number of TH positive cells in the H4 receptor antagonist group was significantly higher than that in the model group (P<0.05). The number of rotations at all the time points in the histamine H4 receptor antagonist group was significantly lower than that in the model group (P<0.05). The dopamine content in the striatum of the model group was significantly lower than that in the control group (P<0.05). The dopamine content in the histamine H4 antagonist group was significantly higher than that in the model group (P<0.05). The number of substantia nigra alpha-synuclein positive bodies in the injured side was significantly higher than that in the normal side in the model group (P<0.05). The number of alpha-synuclein positive bodies in the histamine H4 receptor antagonist group was significantly lower than that in the injured side of the model group (P<0.05). The number of IBA-1 positive cells in the injured substantia nigra of the model group was significantly higher than that of the normal side (P<0.05), and the number of IBA-1 positive cells in the histamine H4 receptor antagonist group was significantly lower than that of the model group (P<0.05), and the number of IBA-1 positive cells in the M1 type microglia inhibitor group was significantly lower than that in the model group (P<0.05). Conclusion: The histamine H4 receptor antagonist can protect the rotenone-induced neuronal injury, and its protective effect may be related to the inhibition of the proliferation and release of M1 microglia.