Protective effect and mechanism of lncRNA Sox2OT overexpression on PC12 cells injury induced by Aβ1-42 / 中华行为医学与脑科学杂志

Objective:To investigate the mechanism of lncRNA Sox2OT in patients with Alzheimer's disease (AD) induced by A type of β peptide (Aβ1-42).Methods:Rat pheochromocytoma cells (PC12 cells) were selected and treated by Aβ1-42 to establish PC12 cell model.PC12 cells were set as blank group before induction to verify the successful construction of the cell model.The induced PC12 cells were divided into control group, Sox2OT overexpression (p-Sox2OT) group, p-Sox2OT empty vector (p-NC) group, inhibited Sox2OT expression (si-Sox2OT) group and si-Sox2OT empty vector (si-NC) group.The proliferation activity of thiazole blue (MTT) was detected.Flow cytometry was used to detect the cell cycle and apoptosis rate after transfection.Results:MTT results showed that compared with the blank group (99.67±10.50), the cell proliferation rate of the control group (29.33±5.51) was significantly reduced ( t=10.27, P<0.05). RT-qPCR results showed that compared with the control group (0.52±0.06), the Sox2OT mRNA expression level in the p-Sox2OT group (2.19±0.16) was significantly increased ( t=16.93, P<0.05). The mRNA expression level of Sox2OT in the si-Sox2OT group (0.22±0.02) decreased significantly ( t=15.28, P<0.05). Compared with the p-NC group (0.53±0.12), The mRNA expression level of Sox2OT in the p-Sox2OT group (2.19±0.16) was significantly increased ( t=16.25, P<0.05). Compared with the si-NC group (0.51±0.09), the mRNA expression level of Sox2OT in the si-Sox2OT group (0.22±0.02) was significantly decreased ( t=16.93, P<0.05). The difference between the control group, the p-NC group and the si-NC group was not statistically significant ( P>0.05). In addition, the cell proliferation ability of the p-Sox2OT group (145.00±5.12) was significantly higher than that of the si-Sox2OT group (23.33±4.93), control group (55.00±5.00), si-NC group (57.33±8.51) and p-NC group (56.00±5.57) ( t=29.65, 21.78, 27.55, 21.35, all P<0.05). The difference in cell proliferation rate between Control group, p-NC group and si-NC group was not statistically significant ( P>0.05). Cell cycle detection experiments showed that the number of cells in the G1 phase of the p-Sox2OT group was significantly lower than that of the control group and p-NC ( t=9.80, 8.57; both P<0.05), while the number of cells in the G2 phase of the p-Sox2OT group was significantly higher than that of the control group and the p-NC group ( t=11.02, 10.25; both P<0.05). The number of cells in the G1 phase of the si-Sox2OT group was significantly higher than that of the control group and the si-NC group ( t=8.22, 3.11, both P<0.05), while the number of cells in the G2 phase of the si-Sox2OT group decreased significantly, compared with the control group and the si-NC group ( t=6.32, 5.33; all P<0.05). There was no statistically significant difference in cell cycle between the control group, the p-NC group and the si-NC group (both P>0.05). In the S phase, the difference between the p-Sox2OT group and the control group was statistically significant ( t=1.84, P<0.05). The number of cells in the G2 phase of the p-Sox2OT group (19.00±1.00) was significantly higher than that of the si-Sox2OT group (3.33±1.53), the control group (10.00±1.00), si-NC group (8.55±0.73) and p-NC group (7.67±1.53) ( t=14.85, 11.02, 10.23, 10.74, all P<0.05). The apoptosis rate of p-Sox2OT group ((3.66±0.26)%) was lower than that of si-Sox2OT group ((14.25±0.80)%), control group ((8.46±0.44)%), si-NC group ((8.78±0.44)%) and p-NC group ((8.40± 0.21)%) ( t=21.81, 16.27, 20.32, 21.35, all P<0.05). For the apoptosis rate, there was no statistically significant difference between control group, p-NC group and si-NC group( P>0.05). In addition, the expression levels of p-PI3K and p-Akt in the p-Sox2OT group were significantly higher than those in the p-NC group ( P<0.05). Compared with the si-NC group, the expression of p-PI3K and p-Akt in PC12 cells in the si-Sox2OT group was significantly decreased ( P<0.05). Conclusion:lncRNA Sox2OT can promote the proliferation of PC12 cells induced by Aβ1-42 and inhibit apoptosis by regulating the PI3K/Akt pathway.

The effects of silica dust on the expression of MyD88 and TRAF6 mRNA of lung macrophages in rats / 中华劳动卫生职业病杂志

Objective@#To investigate the effects of silica dust on the expression of Myeloid differentiation factor 88 (MyD88) mRNA and tumor necrosis factor receptor-associated factor (TRAF6) mRNA of lung macrophages in rats.@*Methods@#Selecting 40 SPF-class Wistar rats with average weight (200±20) g randomly divided into control group and 30 d, 60 d, 120 d experimental groups with 10 rats in each group according to body weight. The experimental groups rats were injected with 1 ml of SiO2 (100 mg/ml) suspension through the trachea into lung only once, then they were respectively killed after 30, 60, 120 days. The control group rats were injected with 1 ml of saline into lung, and killed after 120 days. The lungs of the rats were taken for pathological observation. Lung macrophages were extracted and counted, and their activity was detected by MTT. RT-qPCR was used to assess the relative contents of MyD88 mRNA and TRAF6 mRNA.@*Results@#Silica dust inhalation led to infiltration of lung tissue cells, thickening the alveolar wall and destruction of alveolar structure. The longer the exposure to dust, the more obvious the results were. The number of macrophages in all experimental groups and activity in the 30 d, 60 d groups were significantly higher than that in the control group (P<0.05) . Among them, 30 d group had the largest number and the highest activity. Compared with the control group, the expression of MyD88 mRNA and TRAF6 mRNA of lung macrophages in rats increased in the experimental groups (P<0.05) , especially in the 60 d group.@*Conclusion@#Silica dust inhalation can increase the expression of MyD88 and TRAF6 in macrophages, suggesting that silica dust can induce silicosis fibrosis by activating TLR/NF-κB signal pathway.

Effects of n-hexane on learning and memory and the expressions of nerve growth factor mRNA and nerve growth factor receptor mRNA of brain tissue in mice exposed to N-hexane / 中华劳动卫生职业病杂志

Objective@#To Effects of n-hexane on learning and memory and the expressions of nerve growth factor (NGF) mRNA and nerve growth factor receptor (NGFR) mRNA of brain tissue in mice exposed to N-hexane.@*Methods@#40 Kunming mice were randomly divided into low-dose group, meddle-dose group, high-dose dose group and control group, with 10 mice in each group. All the groups were orally exposed to n-hexane in different doses: low-dose group with 43.5 mg/kg, middle-dose group with 86.5 mg/kg and high-dose group with 173.0 mg/kg, 1 time per day for 20 d. After the poisoning, the Y-arm test and the expressions of NGF mRNA and NGFR mRNA and the concentrations of NGF and NGFR in the brain tissues of each group were measured.@*Results@#In the first Y-arm test, there existed a significant difference in correct reaction rate generally in all groups (P<0.05), and correct reaction rate in the middle-dose group and the high-dose group were low significantly compared with that in the control group(P<0.05). In the second Y-arm test, there existed a significant differences in total electric shock time and correct reaction rate generally in all groups (P<0.01), and the total electric shock time prolonged significantly and the correct response rate decreased significantly in 3 dose groups compared with those of the control group(P<0.05). The expression levels of NGF mRNA in brain tissues of low, meddle and high dose-groups were 0.81±0.66, 0.67±0.37 and 0.69±0.26, and the expression levels of NGFR mRNA were 1.22±0.42, 1.98±0.84 and 2.01±2.01, respectively. Compared with the control group, the expressions of NGF mRNA in the 3 dose groups decreased significantly (P<0.05), and the expression of NGFR mRNA in middle-and high-dose groups increased significantly (P<0.05). The concentrations of NGF in brain tissues of low,meddle and high dose-groups were 39.97±7.24 ng/L, 39.26±7.88 ng/L,31.70±8.21 ng/L,and the concentrations of NGFR were 17.37±6.82 ng/L,21.37±7.16 ng/L, 22.46±7.70 ng/L, respectively. Compared with the control group, the concentrations of NGF in high-dose groups decreased significantly(P<0.05), and the concentrations of NGFR in middle-and high-dose groups increased significantly (P<0.05).@*Conclusion@#N-hexane exposure can result in decrease of learning and memory in mice, which may be related to abnormal expression of NGF mRNA and NGFR mRNA in brain tissue.

Effects of hypothermia on learning and memory ability and expression of fusion gene and fission gene mRNA of mitochondria in hippocampus of rats / 中华行为医学与脑科学杂志

Objective To study the effects of hypothermia on learning and memory ability and mRNA expression of fusion gene and fission gene of mitochondria in hippocampus of rats.Methods 32 Wistar rats were randomly divided into 4 groups according to low-temperature exposure time in the test:high-exposure group(low-temperature exposure for 24 h/d),middle-exposure group(low-temperature exposure for 12 h/d),low-exposure group(low-temperature exposure for 6 h/d) and control group.The temperature of low-temperature exposure was 0-5 ℃.The total test time was 45 d.Morris water maze test was performed on each group from the fifth day before the end of the low-temperature test to the first day after the low-temperature test.After the water maze test,the mRNA expressions of mitochondrial fusion genes (Mfn1,Mfn2) and fission genes(Fis1,Drp1) in hippocampus were detected by RT-qPCR.Results Compared with the control group,the escaping latency of the high-exposure group and the middle-exposure group at the first day and the fifth day of water maze test were significantly longer than those in the control group,and the difference was statistically significant(P＜0.05,P＜0.01).The escaping latency of the sixth day and the number of platform crossings at the beginning of the water maze test were significantly different from those in the control group(P ＜0.05,P＜0.01).Compared with the control group,the escaping latency of the high-exposure group and the middle-exposure group was significantly prolonged on the sixth day,and the number of the platform crossings decreased significantly.The difference was statistically significant (P＜ 0.05,P＜ 0.01).The high,middle and low-exposure group of mitochondrial fusion and fission genes mRNA expressions were as follows respectively:Mfn1:4.05 ±0.21,1.51±0.23,1.17 ±0.83;Mfn2:5.38 ±0.74,0.84 ±0.53,0.47 ±0.33;Fis1:1.65 ±0.58,0.49 ± 0.42,0.40±0.32;Drp1:4.11 ±0.37,0.99 ±0.82,0.55 ±0.29.Compared with the control group,the mRNA expression of the fusion and the fission genes in the high-exposure group increased significantly(P＜0.01).Conclusion The abnormalities of mitochondrial fusion and fission gen mRNA expression in the hippocampus may be one of the mechanisms of the decline of learning and memory functions caused by low temperature exposure.

Effect of silica dust on protein oxidative injury in lung tissue of mice / 中华劳动卫生职业病杂志

Objective@#To investigate the effect of silica dust on protein oxidative injury in the lung tissue of mice.@*Methods@#A total of 60 mice were randomly divided into control group (not exposed to dust) , 2-hour group (inhalation of dust for 2 hours per day) , 4-hour group (inhalation of dust for 4 hours per day) , and 8-hour group (inhalation of dust for 8 hours per day) , with 15 mice in each group. During dust exposure, the mice were placed in a dust exposure cabinet; the dust was blown with an air blower and the concentration was maintained at 125 mg/m3. All mice were exposed to silica dust for 3 weeks. The changes of the lung were observed after dust exposure ended, and spectrophotometry was performed to measure the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) and protein carbonyl in the lung tissue.@*Results@#The 2-, 4-, and 8-hour groups had marked edema, sporadic punctate hemorrhage, and nodular shadow in the lungs. Compared with the control group, the 2-, 4-, and 8-hour groups had a significant increase in lung coefficient (7.03±0.78 mg/g, 8.48±0.93 mg/g, and 8.99±0.85 mg/g vs 5.52±0.81 mg/g, P<0.05) . Compared with the control group, the 2-, 4-, and 8-hour groups had significant increases in the content of MDA (2.83±0.52, 3.94±0.65, and 4.56±0.77 nmol/mg prot vs 1.26±0.36 nmol/mg prot, P<0.05) and protein carbonyl (1.61±0.44, 1.96±0.47, and 2.20±0.58 nmol/mg prot vs 1.13±0.21 nmol/mg prot, P<0.05) in lung tissue. The 4- and 8-hour groups had a significantly lower activity of SOD than the control group (153.69±20.58 and 140.35±18.97 U/mg prot vs 186.00±25.46 U/mg prot, P<0.05) .@*Conclusions@#Silica dust may lead to protein oxidative injury in the lung tissue of mice, which might play an important role in lung injury.

Influence of sodium nitrite exposure on sulfhemoglobin and hydroxyl radicals in mice / 中华劳动卫生职业病杂志

Objective@#To investigate the influence of sodium nitrite exposure on sulfhemoglobin and hydroxyl radicals in mice.@*Methods@#A total of 60 mice were randomly divided into low-, middle-, and high-dose groups (the concentrations of sodium nitrite were 0.055 mg/ml, 0.110 mg/ml, and 0.220 mg/ml, respectively) and control group (treated with distilled water) , with 15 mice in each group (male/female ratio=1: 1) . A free-drink model was applied and the duration of exposure was 2 weeks. The body weight of all mice was recorded before exposure and at weeks 1 and 2 of exposure. At the end of exposure, the mice were treated with intraperitoneally injected sodium salicylate to capture the hydroxyl radicals and produce 2, 5-dihydroxybenzoic acid and 2, 3-dihydroxybenzoic acid, and high-performance liquid chromatography was used to measure their content. Spectrophotometry was used to measure the relative content of sulfhemoglobin.@*Results@#At week 2 of exposure, the low-, middle-, and high-dose groups had significantly lower body weight than the control group (22.8±2.8 g/21.6±2.8 g/21.2±3.0 g vs 25.6±2.2 g, P<0.05) . The low-, middle-, and high-dose groups had a significantly higher total content of hydroxyl radicals than the control group[ (0.015 3±0.006 5) μg/ml, (0.016 4±0.017 2) μg/ml, and (0.062 7±0.091 0) μg/ml vs (0.009 ±0.007 3) μg/ml, P<0.05]. The relative content of sulfhemoglobin was 1.54%±0.73%, 2.22%±0.44%, and 2.80%±0.69%, respectively, in the low-, middle-, and high-dose groups, and the middle- and high-dose groups had a significant increase in the relative content of sulfhemoglobin compared with the control group (2.22%±0.44%/2.80%±0.69% vs 1.76%±0.60%, P<0.05) . The content of hydroxyl radicals was positively correlated with the relative content of sulfhemoglobin (r=0.837, P<0.05) .@*Conclusion@#Sodium nitrite exposure can increase the content of sulfhemoglobin and hydroxyl radicals in blood, and there is a positive correlation between them.

Influence of n-hexane on vascular endothelial active substances in brain tissue in mice / 中华劳动卫生职业病杂志

Objective@#To investigate the influence of n-hexane on vascular endothelial active substances in brain tissue in mice and its significance.@*Methods@#A total of 48 healthy Kunming mice were randomly divided into high-dose exposure group, middle-dose exposure group, low-dose exposure group, and control group, with 12 mice in each group. All groups except the control group were exposed to n-hexane via static inhalation (0.035 g/L, 0.018 g/L, and 0.009 g/L for the high-, middle-, and low-dose exposure groups, respectively) 4 hours a day for 21 days. the mice in the control groups were not exposed to n-hexane. After the exposure, the lev-els of endothelin-1 (ET-1) , nitric oxide (NO) , and angiotensin II (Ang II) in brain tissue were measured in all groups.@*Results@#There were significant differences in the levels of ET-1, NO, and Ang II between the three ex-posure groups and the control group (P<0.05). Compared with the control group, the high-and middle-dose expo-sure group had significant increases in the levels of ET-1 and Ang II and the high-dose exposure group had a sig-nificant reduction in the level of NO (P<0.05 or P<0.01).@*Conclusion@#n-Hexane can affect the vascular endothe-lial active substances in brain tissue in mice, and the changes and imbalance in vascular endothelial active sub-stances may be one of the reasons for central nervous system impairment caused by n-hexane.

Antihypertensive treatment in the prevention and treatment of ischemic stroke: the J-curve phenomenon / 国际脑血管病杂志

The J-curve phenomenon in the antihypertensive treatment of cardiovascular disease has had more theoretical and experimental evidence and has been recognized by most researchers.However,there are a few related studies and reports about whether antihypertensive treatment has the J-curve phenomenon in ischemic stroke.It has not yet reached a consensus.This article reviews this phenomenon and expecting it to contribute to the blood pressure mangement of ischemic stroke.