| 3 | Micronuclei in Nasal Mucosa, Oral Mucosa and Lymphocytes in Students Exposed to Formaldehyde Vapor in Anatomy Class显示文摘The frequency of micronuclei (MN) in cells of the nasal mucosa, oral mucosa and in lym-phocytes was evaluated for 25 students in anatomy classes exposed to formaldehyde (FA) overan 8-week period. Each student served as his or her own control. The time-weighted averageconcentration (TWA) of fOrmaldehyde in anatomical laboratories and in students’ dormitorieswas 0. 508 ± 0. 299 mg/m3 and 0. 012 ± 0. 0025mg/m3, respectively. A higher frequency ofmicronuclei was observed in nasal and oral exfoliative cells after formaldehyde exposure (3. 85± 1. 48 vs 1 .20± 0. 676 and 0. 857 ± 0. 558 vs 0. 568 ± 0. 317, paired-t test: P< 0. 001and P < 0. 01, respectively). No significant increase in the frequency of lymphocyte micronu-clei was found after formaldehyde exposure (P >0. 05 ). The present study shows that nasalmucosa cel1s exposed through respiration are the chief target of FA-induced genotoxic | YING CHEN -JlANG YAN WEN-SHENG ZHAO MEI-YING YE XIAO-LEI XIE HONG YIN SHU-YI ZHU XIAN-SHU(Department of Environmental Health, n Dgurtment of Anatomy,Tongji the ical University, Wuhan, China)(Department of Public Health, Wengzhou theical Chllege, Ch | 1997 | Biomedical and Environmental Sciences1997，10，4： | 7 |
| 5 | Neuroprotective effects of INT-777 against Aβ1-42-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice显示文摘OBJECTIVE To investigate the neuroprotective effects of TGR5 agonist INT-777 in the Aβ_(1-42)-treated mouse model of acute neurotoxicity.METHODS Cognitive impairment was induced by single intracerebroventricular injection of aggregated Aβ_(1-42)(410 pmol per mouse;5 μL)into the mouse brain in normal ICR mice.After3 d,INT-777(0.75,1.5 or 3.0 μg per mouse) was infused into the same site.Another 3 d later,the cognition function was evaluated by Morris water maze(MWM),novel objective recognition(NOR),and Y maze tests.Furthermore,the levels of TGR5,TNF-α,IL-1β,IL-6,NF-κB p65,Iba1,caspase 3,Bcl-2,Bax,PSD95,and synaptophysin in the hippocampus and frontal cortex were detected using Western blotting.Microglia activation in the hippocampal CA1,CA3 and DG regions and frontal cortex were detected by immunohistochemistry.TUNEL staining was used to detect the apoptotic cells.The number of spines in the hippocampal CA1,CA3 and DG regions and frontal cortex was detected by GolgiCox staining.RESULTS INT-777(1.5 or 3.0 μg per mouse) significantly ameliorated memory impairment in the Aβ_(1-42)-treated mice,evidenced by increased the time spent in the target quadrant(P<0.05),and the number of target crossings(P<0.05) in the MWM test,increased the discrimination index in the NOR test(P<0.05),and increased the number of correct choices(P<0.05,P<0.01) and decreased the latency(P<0.05) to enter the shock-free compartment in the Y-maze test.Importantly,this treatment reversed Aβ_(1-42)-induced TGR5 down-regulation(P<0.05,P<0.01),suppressed the increase of nuclear NF-κB p65(P<0.05,P<0.01) and mitigated neuroinflammation,evidenced by lower proinflammatory cytokines such as TNF-α(P<0.05),IL-1β(P<0.05),IL-6(P<0.05,P<0.01),and less Iba1-positive cells in the hippocampal CA1,CA3 and DG regions and frontal cortex(P<0.05,P<0.01) as well as the protein level of Iba1.INT-777(1.5 or3.0 μg per mouse) also pronouncedly suppressed apoptosis through the reduction of TUNEL-positive cells(P<0.05,P<0.01),decreased activation of caspase 3(P<0.05),increased ratio of Bcl-2/Bax(P<0.05,P<0.01),and ameliorated synaptic dysfunction via promoting dendritic spines generation(P<0.05,P<0.01) with the upregulation of PSD95(P<0.05) and synaptophysin proteins(P<0.05).CONCLUSION INT-777 has potent neuroprotective effects against Aβ_(1-42)-induced neurotoxicity,which suggests that the activation of TGR5 could be a novel and promising strategy for the treatment of AD. | WU Xian LYU Yang-ge DU Yi-feng CHEN Fang Miranda N REED HU Mei Vishnu SUPPIRAMANIAM TANG Su-su HONG Hao | 2018 | 中国药理学与毒理学杂志2018，32，9： | 6 |
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