Objective:To investigate the effects of different doses of sodium arsenic (NaAsO 2) on mRNA transcription levels of nucleotide excision repair (NER) related genes in normal hepatocytes (L-02 cells) and the modification levels of histone H3 ninth lysine dimethylization (H3K9me2) in the promoter region. Methods:L-02 cells were treated with 0 (the control group) , 5, 10 and 20 μmol/L NaAsO 2 for 24 h ( n = 3). Single cell gel electrophoresis (SCGE) was used to detect DNA damage [Olive tail distance (OTM) and Tail DNA percentage (Tail DNA%)] in L-02 cells. The mRNA expression levels of Xeroderma pigmentosum (XP) gene A (XPA), XP gene D (XPD) and XP gene F (XPF) were detected by real-time fluorescence quantitative PCR. The modification levels of H3K9me2 in XPA, XPD and XPF gene promoter regions (CHIP1 and CHIP2) were detected by quantitative chromatin immunoprecipitation. Results:OTM and Tail DNA% were positively correlated with arsenic doses (in the control and 5, 10 and 20 μmol/L arsenic exposure groups, the values were 0.35 ± 0.09, 0.56 ± 0.18, 3.18 ± 0.31, 4.52 ± 0.55, 0.72 ± 0.05, 1.34 ± 0.26, 3.93 ± 0.43, 5.47 ± 0.65, respectively, r = 0.927, 0.948, P < 0.05). Compared with the control group, the mRNA expression levels of XPA, XPD and XPF in L-02 cells of 10 and 20 μmol/L arsenic exposure groups were significantly lower ( P < 0.05). Compared with the control group, the enrichment levels of H3K9me2 in XPA, XPD and XPF gene promoter regions (CHIP1 and CHIP2) in L-02 cells of 20 μmol/L arsenic exposure group were significantly higher ( P < 0.05). Conclusion:Arsenic may inhibit the transcription of NER related genes by increasing the enrichment level of H3K9me2 in the promoter regions (CHIP1 and CHIP2) of NER related genes, thereby reduce the DNA damage repair ability of L-02 cells, resulting in the aggravation of DNA damage.

Objective:To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats.Methods:From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl 2·4H 2O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl 2·4H 2O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results:The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased ( P<0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased ( P<0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day ( P<0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased ( P<0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened ( P<0.05) , and the average number of crossing the original platform was increased ( P<0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups ( P<0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased ( P<0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese ( P<0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group ( P<0.05) . Conclusion:Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.

Objective:To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats.Methods:From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl 2·4H 2O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl 2·4H 2O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results:The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased ( P<0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased ( P<0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day ( P<0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased ( P<0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened ( P<0.05) , and the average number of crossing the original platform was increased ( P<0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups ( P<0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased ( P<0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese ( P<0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group ( P<0.05) . Conclusion:Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.