关键词: 精神分裂症, 淫羊藿苷, NRG1/ErbB4信号通路, 氧化应激, 炎症反应, 认知, 大鼠

Abstract: BACKGROUND: Icariin is one of the effective active components of Epimedium, which is important for reinforcing kidney and strengthening yang. It can not only promote the function of the reproductive system, but also significantly improve schizophrenia. However, its specific mechanisms of action are still in study and exploration phase.
OBJECTIVE: To explore the effects and mechanisms of icariin on cognitive function of schizophrenia rats. 
METHODS: A total of 48 Sprague-Dawley rats were randomly divided into control group, model group, low-dose and high-dose icariin groups with 12 rats in each group. Except for the control group, schizophrenia models were established in the other groups by intraperitoneal injection of N-methyl-D-aspartate receptor antagonist, MK-801, once a day for continuous 14 days. After modelging, the rats in the low- and high-dose icariin groups were intragastrically given icariin, 25 and 50 mg/kg per day for 28 days, respectively, while those in the control and model groups were given the same amount of normal saline. After administration, behavioral detection, Nissl staining and FJB staining of the hippocampus were performed. Oxidative stress level, inflammatory factor level, and NRG1/ErbB4 signaling pathway protein expression were detected.
RESULTS AND CONCLUSION: Compared with the model group, stereotyped behavior score, total distance of spontaneous activities and escape latency were significantly decreased, while times of crossing the platform were significantly increased in the two administration groups (P < 0.05). The stereotyped behavior score and escape latency (days 3-5) in the high-dose icariin group were significantly lower than those in the low-dose icariin group (P < 0.05). Compared with the model group, mitochondrial membrane potential and superoxide dismutase activity in the hippocampus were significantly increased, while the levels of malondialdehyde, interleukin-6, interleukin-1β, and tumor necrosis factor-α were significantly decreased in the two administration groups (P < 0.05). Compared with the low-dose icariin group, superoxide dismutase activity was significantly increased and the levels of malondialdehyde, interleukin-6, interleukin-1β, and tumor necrosis factor-α were significantly decreased in the high-dose icariin group (P < 0.05). Compared with the model group, expressions of NRG1 and ErbB4 proteins in the hippocampus were significantly decreased in the two administration groups (P < 0.05). Compared with the low-dose icariin group, the expression of ErbB4 protein was significantly decreased in the high-dose icariin group (P < 0.05). Nissl staining and FJB staining of the hippocampus showed that the number of Nissl bodies in the hippocampus was significantly reduced in the model group, while the number of FJB-positive cells in the CA1 and CA3 regions was significantly increased; compared with the model group, the number of Nissl bodies in the hippocampal was significantly increased in the low-dose and high-dose icariin groups, while the number of FJB positive cells in CA1 and CA3 regions was significantly decreased. To conclude, icariin can improve cognitive function in rats with schizophrenia. And its mechanisms may be related to regulating expressions of NRG1/ErbB4 signaling pathway proteins and reducing oxidative stress and inflammatory responses.

Key words: schizophrenia, icariin, NRG1/ErbB4 signaling pathway, oxidative stress, inflammatory response, cognition, rat