关键词:  , 苯并［a］芘, 胰岛素降解酶, 脑啡肽酶, 神经胶质

Abstract: Objective： To investigate effects of benzo(a)pyrene (BaP) on expressions of insulin-degrading enzyme (IDE) and neprilysin (NEP) which have the ability to degrade β-amyloid (Aβ) in neu-roglia cells. Methods: Primary mix-neuroglia cells were cultured from newborn SD rats. After exposure to BaP, Aβ1-42 oligomer or Aβ1-42 fiber individually or jointly for 24 h, the cell survival rate was mea-sured by cell counting kit-8 (CCK-8). Afterwards, the primary mix-neuroglia cells were divided randomly into six groups: Control group, BaP group (2.00 μmol/L), Aβ1-42 oligomer group (20.00 mg/L), BaP plus Aβ1-42 oligomer group, Aβ1-42 fiber group (20.00 mg/L) and BaP plus Aβ1-42 fiber group, of which BaP was pretreated for 12 h followed by cotreatment with different aggregated Aβ1-42. The expressions of IDE and NEP were measured by quantitative real-time polymerase chain reaction (qRT-PCR) for mRNA level and Western blotting for protein level. Results： The cell survival rate showed no significant differences after treatment with BaP (≤20.00 μmol/L), Aβ1-42 oligomer (20.00, 40.00 mg/L), Aβ1-42 fiber (20.00, 40.00 mg/L) or cotreatment with BaP and Aβ1-42 oligomer or BaP and Aβ1-42 fiber. Compared with the control group, expressions of IDE and NEP in BaPtreated alone group had no obvious change; however, exposure to Aβ1-42 oligomer alone significantly increased the mRNA and protein level of IDE (P<0.05), and the BaP pretreatment could significantly inhibit the up-regulated expressions of IDE by Aβ1-42 oligomer (P<0.05); on the other hand, exposure either to Aβ1-42 fiber alone or under the BaP pretreatment did not change the mRNA and protein level of IDE and NEP obviously. Conclusion: On the premise of no significant change of cell survival rate, BaP pretreatment inhibited the up-regulated expressions of IDE in primary mixed neuroglia cells under cotreatment with Aβ oligomer, indicating that BaP may disturb degradation of Aβ oligomer and cause deposition of β-amyloid and further induce cognitive decline and acceleration of Alzheimer.

Key words: Benzo(a)pyrene, Insulin-degrading enzyme, Neprilysin, Neuroglia