Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage

Objective To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage. Methods Sixty SD rat aged 9–12 weeks were chosen and divided into the control group, model group and simvastatin-treated group randomly with 20 rats in each group. Rats in the model group and simvastatin-treated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model, while rats in the control group were treated with the same amount of normal saline. Then, rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling. Rats in the three groups were given nerve dysfunction score (NDS) and wet-dry weighting method was used to detect the brain water content (BWC) of brain tissues around the lesion of the rats. Then Nissl staining was conducted and the undamaged neurons were counted. Immunohistochemical SP method was applied to count the number of NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions, and the immuno fluorescence method was employed to determine the expression levels of NF-κB, TLR4 and IL-1β proteins. Results The NDS results of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods (P < 0.05); the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); seven days after treatment, the number of the NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group (P < 0.05), and its expression levels of NF-κB, TLR4 and IL-1β protein were also significantly lower than those of the model group (P < 0.05). Conclusions Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage

OBJECTIVE@#To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.@*METHODS@#Sixty SD rat aged 9-12 weeks were chosen and divided into the control group, model group and simvastatin-treated group randomly with 20 rats in each group. Rats in the model group and simvastatin-treated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model, while rats in the control group were treated with the same amount of normal saline. Then, rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling. Rats in the three groups were given nerve dysfunction score (NDS) and wet-dry weighting method was used to detect the brain water content (BWC) of brain tissues around the lesion of the rats. Then Nissl staining was conducted and the undamaged neurons were counted. Immunohistochemical SP method was applied to count the number of NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions, and the immuno fluorescence method was employed to determine the expression levels of NF-κB, TLR4 and IL-1β proteins.@*RESULTS@#The NDS results of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods (P < 0.05); the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); seven days after treatment, the number of the NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group (P < 0.05), and its expression levels of NF-κB, TLR4 and IL-1β protein were also significantly lower than those of the model group (P < 0.05).@*CONCLUSIONS@#Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

P38MAPK pathway regulates COX-2 and caspase-3 expression in a mouse model of Parkinson disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of p38 mitogen-activated protein kinase (p38MAPK) on the expression of COX-2 and caspase-3 in the substania nigra (SN) of mice with MPTP-induced Parkinson disease (PD).</p><p><b>METHODS</b>C57BL/CN mice were treated with MPTP to prepare a subacute PD model, and their behavioral changes following the treatment were observed. Immunohistochemistry and Western blotting were performed to detect the expression of tyrosine hydroxylase (TH), COX-2 and phosphorylation of P38MAPK in the SN and their changes following treatment with SB203580, a specific inhibitor of P38MAPK.</p><p><b>RESULTS</b>The 7-day model group showed typical symptoms of PD with decrements of TH-positive neurons and TH protein level in the SN of the midbrain by about 65% and 75%, respectively (P<0.01). In the 3-day model group, the COX-2-, caspase-3- and phosphorylated P38MAPK-immunoreactive cells and their protein levels in the SN increased markedly with obvious loss of TH-positive neurons. Administration of SB203580 obviously lessened the above changes (P<0.01).</p><p><b>CONCLUSION</b>P38MAPK regulates the inflammation and apoptosis in the SN of the mouse model of subacute PD, and SB203580 may provide some neuroprotective effect.</p>

Effect of phosphorylated c-Jun expression on COX-2 expression in the substantia nigra of MPTP mouse model of subacute Parkinson disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of phophorylated c-Jun (p-c-Jun) expression on the expression of COX-2 in the substantia nigra (SN) of the MPTP mouse model of subacute Parkinson disease (PD) and explore the possible mechanism of the dopaminergic (DA) neuron death in PD.</p><p><b>METHODS</b>C57BL/6N mice were treated with MPTP to establish subacute PD model. The changes of TH-, COX-2- and p-c-Jun-positive cells, and the expression levels of TH, COX-2 and p-c-Jun in the SN in the midbrain were observed with inmmunohistochemistry and Western blotting before and after administration of SP600125, a specific JNK inhibitor.</p><p><b>RESULTS</b>Compared with the mice in control group, the PD mice exhibited typical symptoms of PD. The number of TH-positive neurons and expression level of TH in the model group were significantly reduced in the substantia nigra by about 65% and 75% (P<0.001) 7 days after the fifth injection of MPTP. The number of COX-2-immunoreactive cells and the expression level of COX-2 were significantly increased. P-c-Jun was specifically expressed in the nuclei of neurons and p-c-Jun expression level was significantly increased in the SN 6 h after the third injection of MPTP. Double-labeling immunofluorescence assay showed coexpression of COX-2 and p-c-Jun in TH-positive neurons in the SN. In mice treated with JNK inhibitor, the number of TH-positive neurons and TH expression level in the SN was only decreased by 15% and 20% as compared with the control group (P<0.001) 7 days after the fifth injection of MPTP, COX-2-positive cell number and COX-2 expression level were obviously reduced as compared with the model group (P<0.001), and p-c-Jun was expressed mainly in the cytoplasm of the neurons whose expression level in SN were significantly decreased 6 h after the third injection of MPTP. The PD mice treated with SP600125 showed slight behavioral symptoms.</p><p><b>CONCLUSION</b>P-c-Jun expression may play an important role in mediating COX-2 expression in the SN in the MPTP model of subacute PD, and inhibiting p-c-Jun activity may provide neuroprotection to the mouse model.</p>