Abstract: The purpose of this study was to explore the protective effect of melatonin (MT) on hippocampal inflammatory injury induced by lipopolysaccharide (LPS) in rats. Forty 4-week-old healthy male SD rats were randomly divided into 4 groups:control group (CON group), model group (LPS group), MT intervention group (LPS+MT group) and MT group. Four hours after intraperitoneal injection of 10 mg·kg^-1 MT and/or 10 mg·kg^-1 LPS, the behavior of rats was tested by open field test. The hippocampus was weighed and coefficient of hippocampus was calculated. The pathological changes of the hippocampal region of brain were observed by hematoxylin-eosin (HE) staining. The mRNA expressions of microglial activation markers Iba-1 and CD11b in hippocampus were detected by RT-PCR. The protein expressions of inflammatory cytokines IL-1β, TNF-α, IL-6, IL-10 and TGF-β in hippocampus were detected by Weston blot. The results showed that compared with CON group, the autonomous exploration behavior and motor ability of rats in LPS group were decreased; the arrangement of nerve cells in hippocampus was loose, and the intercellular space of hippocampus was enlarged, cytoplasmic pyknosis was deeply stained, glial cells were infiltrated; the expression of microglia activation markers Iba-1 and CD11b mRNA were significantly increased (P<0.01); the protein expressions of pro-inflammatory factors IL-1β, TNF-α and IL-6 were significantly increased in LPS group (P<0.01); the protein expression of anti-inflammatory factors IL-10 and TGF-β decreased significantly (P<0.01). Compared with LPS group, the autonomous exploration behavior and motor ability of rats in LPS+MT group were increased; the arrangement of nerve cells in hippocampus was compact, and there was no obvious pathological change; the mRNA expressions of microglia activation markers Iba-1 and CD11b were significantly decreased (P<0.01); the protein expressions of pro-inflammatory factors IL-1β, TNF-α and IL-6 were significantly decreased in LPS+MT group (P<0.01); the protein expression of anti-inflammatory factors IL-10 and TGF-β increased significantly (P<0.1). In addition, there was no significant difference in all indexes between MT group and CON group (P>0.05). The above results suggest that MT can inhibit the activation of microglia and reduce the inflammatory response of hippocampus, thus improving the inflammatory injury of hippocampus induced by LPS in rats.

Key words: melatonin, LPS, hippocampal inflammation, microglia, sepsis, rat