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AIM:To observe the mechanism of Tianma Gouteng Decoction on the protein molecular level in the optic nerve crush model rats.METHODS:Totally 36 participants 36 male Wistar rats were divided randomly into six groups(6 in every group):normal control group,negative control group,Tianma Gouteng Decoction treatment groups (con-centrations were 0.6g/mL,1.2g/mL,2.4g/mL respictively) and ginkgo biloba tablets positive control group (concentrations was 1.2mg/mL).Nothing was done in the normal control group.The optic nerve of right eye in the other groups was done with the optic nerve crush model.Normal control group and negative control group was treated only with water.The average grey scale values of the N-methyl-D-aspartic acid receptor 2B (NMDA2B) receptor protein,beta-amyloid protein (Aβ) in the average grey scale values were detected.RESULTS:The average grey scale value of Tianma Gouteng Decoction in low,medium and high dose groups about NMDA2B receptor protein was significantly less than that of the negative control group (all P＜0.001),and there was no significant difference with the positive control group (P=0.092,0.411,0.676),the difference between normal control group and negative control group was significant (P＜0.001).The high dose group of betaamyloid's average grey scale value reduced significantly than the negative control group (P=0.030,0.001).The low dose group than the negative control group was not obviously (P=0.614).The high dose group was not significantly different from the positive control group (P=0.927),the difference between normal control group and negative control group was significant (P＜0.001).CONCLUSION:Tianma Gouteng Decoction can go through the decrease of the NMDA2B receptor protein expression and the control of beta-amyloid deposition to reduce the retinal ganglion cell injury and apoptosis.
ABSTRACT
Objective Spinal cord injury-induced neuropathic pain(NP)does not respond well to any existing therapies clinically.This study aimed to explore the molecular metabolisms neuropathic pain by observing the expressions of the N -methyl-D-as-partic acid receptor 2B(NR2B),tumor necrosis factor-alpha(TNF-α)and brain-derived neurotrophic factor(BDNF)in different sta-ges of the condition in SD rats. Methods Thirty-six adult SD rats were randomly divided into a control,a sham operation and an NP model group.The NP model was established by spinal nerve ligation. At 5 and 14 days after modeling,the hindlimb motor function and paw withdrawal threshold(PWT)of the rats were evaluated by the open-field test and the expressions of NR 2B,TNF-αand BDNF in the dor-sal root ganglia of the L4-6 spinal cord were determined by Western blot. Results At 5 days after modeling,the open-field test showed a significantly shorter total distance of movement in the sham operation group than in the control([14 927.93 ±560.87]vs [18 225.15±371.76]mm,P<0.05)and even shorter in the NP model group([3 224.92±89.64]vs[18 225.15±371.76]mm, P<0.01).The time of activity was markedly decreased in the NP model group as compared with that in the control([203.48±19.94]vs [745.95±13.48]s,P<0.01),but with no statistically significant difference between the sham operation and control groups([727.93± 16.29]vs[745.95±13.48]s,P>0.05).At 14 days after modeling,both the total distance of movement and time of activity were re-markably shorter in the NP model than in the sham operation and control groups([3 395.53±96.12]vs[17 382.26±482.31]and [17 975.40±416.56]mm,P<0.01;[195.53±96.12]vs[739.31±18.36]and[775.20±16.84]s, P<0.01).The PWT showed no statistically significant difference among the three groups of rats before modeling(P>0.05)but markedly decreased in the NP model as compared with the sham operation and control groups(P<0.01),with no significant difference between the latter two(P>0.05).The expressions of NR2B,TNF-αand BDNF were remarkably up-regulated in the NP model group in comparison with the sham operation and control groups at 5 days after modeling(P>0.05)and even more significantly at 14 days(P<0.01). Conclusion NR2B and BDNF may be involved in the development and progression of neuropathic pain in rats.
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<p><b>OBJECTIVE</b>To study the effect of chronic noise exposure on expression of N-methyl-D-aspartic acid receptor 2B (NR2B) and tau phosphorylation in hippocampus of rats.</p><p><b>METHODS</b>Twenty-four male SD rats were divided in control group and chronic noise exposure group. NR2B expression and tau phosphorylation in hippocampus of rats were detected after chronic noise exposure (100 dB SPL white noise, 4 h/d×30d) and their mechanisms underlying neuronal apoptosis in hippocampus of rats with TUNEL staining.</p><p><b>RESULTS</b>The NR2B expression decreased significantly after chronic noise exposure which resulted in tau hyperphosphorylation and neural apoptosis in hippocampus of rats. Immunohistochemistry showed that the tau hyperphosphorylation was most prominent in dentate gyrus (DG) and CA1 region of rat hippocampus.</p><p><b>CONCLUSION</b>The abnormality of neurotransmitter system, especially Glu and NR2B containing NMDA receptor, and tau hyperphosphorylation in hippocampus of rats, may play a role in chronic noise-induced neural apoptosis and cognition impairment.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Hippocampus , Cell Biology , Metabolism , Neurons , Cell Biology , Metabolism , Noise , Phosphorylation , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate , Metabolism , tau Proteins , MetabolismABSTRACT
Objective To investigate the influence of Memantine on changes of N-methyl-D-aspartic acid receptor 2B (NMDAR-2B) level, the expression of postsynaptic density 95 ( PSD-95) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)activities in the hippocampus of vascular dementia(VD)rats and their recognition. Methods The VD rat model was established by permanent,bilateral occlusion of the common carotid arteries. One hundred and forty-four Wistar rats were randomly divided into sham-operated group, VD model group and Memantine-treated group. The water maze test was performed to detect the ability of learning and memory of the rats,the changes of NMDAR-2B level were measured by RT-PCR,the changes in the expression of PSD-95 were detected by immunohistochemical staining,and the changes in the CaMK Ⅱ activities were determined by incorporation of ~(32)P into histone. Results Compared with the sham-operated group, the ability of learning and memory of VD rats was decreased significantly(P<0. 01); the level of NMDAR-2B and the expression of PSD-95 increased significantly at the 4th week after operation(F<0. 05 or 0. 01)and decreased at the 8th to 16th week after operation (P<0. 01). Total CaMK Ⅱ activity was increased significantly at the 4th week after operation(P<0. 01) ,then dropped at the 8th week after operation(P>0. 05) ,and decreased significantly at the 12th,16th week after operation(P<0. 01). As for Memantine-treated group,at the 4th week after operation,there was no statistically significant difference in the parameters mentioned above in contrast with the sham-operated group. At the 8th,and 12th week after operation,the ability of learning and memory,the level of NMDAR-2B and the expression of PSD-95 were significantly increased as compared with VD rats(P<0. 01 or 0. 05) ,but total CaMK Ⅱ activity was similar to that of VD rats. Conclusion With the development of VD,NMDAR-2B level,the expression of PSD-95 and CaMK Ⅱ activities were firstly over-activated,and then decreased greatly. Memantine can improve VD rats' recognition by modulating the expression of NMDAR-2B,but its effect on CaMK Ⅱactivity was limited.
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Objective To investigate changes of N-methyl-D-aspartic acid receptor 2B(NR2B) level and calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ) activities in the hippocampus of vascular dementia(VD) rats and the intervention effects of Memantine.Methods The VD rat models were established by permanent,bilateral occlusion of the common carotid arteries.The rats were randomly divided into VD group and Memantine-treated group.At 4,8,12,16 weeks after operation,the water maze test was performed to detect the ability of learning and memory of the rats.The changes of NR2B level were measured by RT-PCR.The changes of the CaMK Ⅱ activities were determined by incorporation of 32P into histone.The resoults were compared with the sham-operated group.Results Compared with the sham-operated group,the ability of learning and memory of VD group rats at each time point after operation decreased significantly(all P