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OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats. METHODS Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF- α， IL-6 and IL-1β， the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus （P＜0.05）； the escape latency time was shortened significantly （P＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （P＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （P＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （P＜0.05）. CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway， thus reducing hippocampal neuronal damage.
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Objective:To explore the expressions of estrogen receptor α (ERα) and estrogen receptor β (ERβ) in Chinese female esophageal squamous cell carcinoma (ESCC) and their relationship with clinical pathological characteristics, marriage and childbearing factors and their prognostic impact.Methods:A total of 110 female patients with primary ESCC in Nanyang Center Hospital from January 2001 to December 2016 were selected. The expression levels of ERα and ERβ proteins were examined by immunohistochemistry (IHC). Logistic regression was used to analyze the correlations of ERα and ERβ expressions with marriage and childbearing factors (menstrual status, age of menarche, age of first birth and the number of pregnancy) and clinical pathological parameters (tumor location, tumor invasion depth, lymph node metastasis and tumor stage). Kaplan-Meier method was used for survival analysis and log-rank test was used. Cox proportional hazard model was used for survival multivariate analysis.Results:The expression rates of ERα and ERβ proteins were 37.3% (41/110) and 64.5% (71/110) in tissues of female ESCC patients, respectively. ERβ expression was closely correlated with tumor location ( χ2 = 0.999, P = 0.030), tumor stage ( χ2 = 11.097, P < 0.01) and the number of pregnancy ( χ2 = 6.304, P = 0.012). The number of pregnancy ( HR = 2.553, 95% CI 1.051-6.203, P = 0.039) and ERβ expression ( HR = 2.580, 95% CI 1.966-3.386, P < 0.01) were independent protective factors for the survival of patients. Furthermore, ERα expression ( HR = 0.530, 95% CI 0.384-0.739, P < 0.01) and lymph node metastasis ( HR = 0.663, 95% CI 0.512-0.858, P = 0.002) were independent risk factors for survival. Conclusion:ERα and ERβ expressions can predict the prognosis of female ESCC patients.