Adiponectin alleviates LPS-induced inflammatory response of microglia through A20/NLRP3/caspase-1 pathway / 西安交通大学学报(医学版)

【Objective】 To explore the mechanism of adiponectin (APN) on lipopolysaccharide (LPS)-induced microglial inflammatory response. 【Methods】 After APN intervention or/and LPS stimulation, microglia were harvested and divided into control group, APN group, LPS group, and LPS+APN group. The expressions and secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in microglia were detected by q-PCR and ELISA assay, respectively. The expressions of tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and caspase-1 were detected by Western blot. After silencing A20 expression in the microglia, the cells were treated with APN, and the expressions of A20, NLRP3 and caspase-1 were detected by Western blot again. 【Results】 The mRNA transcription levels (P=0.018, P=0.009) and secretion (P=0.000 1, P=0.000 1) of TNF-α and IL-1β in LPS-induced microglia were significantly decreased after APN intervention. Moreover, the expression of A20 was increased while the expressions of NLRP3 and caspase-1 declined in microglia of LPS+ APN group when compared with LPS group (P=0.001, P=0.003, P=0.006). However, the down-regulated expressions of NLRP3 and caspase-1 by APN were reversed by A20 silencing in microglia (P=0.012, P=0.024). 【Conclusion】 APN can inhibit NLRP3 and caspase-1 expressions in microglia by the up-regulated expression of A20 protein.

Effect of curcumin on learning-memory ability and expression of HMGB1 and JNK in rat model of Alzheimer disease / 中国病理生理杂志

AIM:To evaluate the effect of curcumin on impaired learning-memory ability and the expression of high mobility group box protein 1 ( HMGB1 ) and c-Jun N-terminal kinase ( JNK ) in a rat model of Alzheimer disease (AD).METHODS:Male Sprague-Dawley rats, weighing 250~270 g, were randomly divided into 4 groups (n=9):blank control group (group A), model group (group B), curcumin treatment group (group C, curcumin injected intraper-itoneally at 100 mg· kg-1· d-1 for 6 consecutive days) and solvent control group (group D).The rats of AD model were induced by injection of ibotenic acid into the nucleus basalis of Meynert ( NBM) bilaterally.All rats were trained in Morris maze to assess the ability of learning and memory .The expression of HMGB1 and JNK in the hippocampus was detected by the methods of immunohistochemistry and Western blotting .RESULTS:Compared with group A , the average escape laten-cy (AEL) in groups B and D were obviously longer (P0.05).No significant difference in the expression of HMGB1 in the hippocampus among the 4 groups was found (P>0.05).However, compared with groups B and D , the expression of JNK in group C was decreased obvi-ously (P<0.05).CONCLUSION: Curcumin significantly improves the learning and memory ability of AD rats .The probable mechanisms may be related to inhibiting the release of HMGB 1 from the nucleus of hippocampal neurons and de-creasing the expression of JNK in the hippocampus .