Role of TNF-αin propofol-induced neuronal apoptosis and long-term cognitive impairment in neonatal rats
10.3969/j.issn.1001-1978.2016.07.012
- VernacularTitle:TNF-α在丙泊酚诱发的神经元凋亡及认知功能障碍中的作用
- Author:
Xiaoyuan DENG
;
Bo CHEN
;
Hongliang LIU
;
Tijun DAI
- Publication Type:Journal Article
- Keywords:
propofol;
Tumor necrosis factor-α;
neu-roinflammation;
neuronal apoptosis;
cognitive func-tion;
developing brain
- From:
Chinese Pharmacological Bulletin
2016;32(7):945-949
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the role of TNF-αin propofol-induced neuronal apoptosis and long-term cog-nitive impairment in neonatal rats .Methods Seven-day-old SD rats were randomly divided into 3 groups:Control group ( n =12 ) , P ( single ) group ( n =6 ):propofol 50 mg · kg -1 was injected intraperitoneally (ip.)once;P(repeated) group(n=6):propofol 50 mg · kg -1 was injected ip.once daily, and for seven times. Hippocampal TNF-αlevel was measured 2 hours after propofol anesthesia , there were two time points(n=6) in Control group as control levels (post-natal day 7 for P ( single ) group and postnatal day 13 for P ( repeated ) group ) .In another experiment , 7-day-old rats were randomly divided into 5 groups:Con-trol group; P ( single ) group; P ( repeated ) group; P ( single ) +ETN group: ETN ( etanercept ) 0.4 mg · kg -1 was injected intracerebroventricularly 30 min be-fore propofol administration; P ( repeated ) +ETN group:ETN 0.4 mg· kg -1 was injected intracerebrov-entricularly 30 min before the 1st and 4th administration of propofol , which was injected ip .for seven times , once daily .Hippocampal neuronal apoptosis was detec-ted at postnatal day 7 [ P ( repeated ) and P ( repeated )+ETN groups not involved at this time point ] , 13, 21 and 35 , cognitive function was measured at postnatal day 36 to 41 using Morris water maze test .Results Propofol with different exposure times could increase hippocampal TNF-αlevels(P<0.05,P<0.01);in P ( single ) group, active caspase-3 positive neurons in hippocampal pyramidal cell layer were much greater than control level only at postnatal day 7 ( P<0.05 ) , there were no changes of escape latency or platform crossing times compared with control ( P>0.05 );in P ( repeated ) group, active caspase-3 positive neurons were more significantly increased at postnatal day 13, 21 and 35 than those in control group ( P<0.01 ) , es-cape latency was increased or platform crossing times were decreased more significantly than control in Morris water maze test ( P <0.01 ); after etanercept was ad-ministered intracerebroventricularly , there were no sig-nificant changes of active caspase-3 positive neurons , escape latency and platform crossing times after propo-fol anesthesia compared with control ( P>0.05 ) .Con-clusion TNF-αmediates hippocampal neuronal apop-tosis and long-term cognitive impairment induced by propofol in neonatal rats , and long-term cognitive im-pairment may be related with persistent neuronal apop-tosis.
