Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral...Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral ischemia/reperfusion injury rat model was established using a modified four-vessel occlusion method. Rats were treated with different doses of tea polyphenols (25, 50, 100, 150, 200 mg/kg) via intraperitoneal injection. Results showed that after 2, 6, 12, 24, 48 and 72 hours of reperfusion, peroxide dismutase activity and total antioxidant capacity in brain tissue gradually increased, while malondialdehyde content gradually decreased after tea polyphenol intervention. Tea polyphenols at 200 mg/kg resulted in the most apparent changes. Terminal deoxynucleotidyl transferase-mediated nick end labeling and flow cytometry showed that 200 mg/kg tea polyphenols significantly reduced the number and percentage of apoptotJc cells in the hippocampal CA1 region of rats after cerebral ischemia/reperfusion injury. The open field test and elevated plus maze experiments showed that tea polyphenols at 200 mg/kg strengthened exploratory behavior and reduced anxiety of cerebral ischemia/reperfusion injured rats. Experimental findings indicate that tea polyphenols protected rats against cerebral ischemia/ reperfusion injury and 200 mg/kg is regarded as the optimal dose.展开更多
BACKGROUND: Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases (JNKs) signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. ...BACKGROUND: Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases (JNKs) signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE: To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi'an Jiaotong University from June 2007 to September 2008. MATERIALS: SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK (Thr183/Tyr185) polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 (XRCC1) and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS: A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group (I/R group) were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group (pre-SP group) was given 10 μL SP600125 (3 μg/μL). Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES: Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS: Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased (P 〈 0.01). Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased (P 〈 0.01). Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased (P 〈 0.05) following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group (P 〈 0.05). Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region (r = -0.983, -0.953, P 〈 0.01). CONCLUSION: SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.展开更多
BACKGROUND: Cognitive dysfunction occurs in elderly patients following general anesthesia, and this might be associated with genetics. Studies have shown that the ε4 allele gene is closely associated with senile dem...BACKGROUND: Cognitive dysfunction occurs in elderly patients following general anesthesia, and this might be associated with genetics. Studies have shown that the ε4 allele gene is closely associated with senile dementia. OBJECTIVE: To compare and analyze the correlations between cognitive dysfunction and single nucleotide polymorphism of apolipoprotein E (ApoE) following inhalation or intravenous anesthesia. DESIGN, TIME AND SETTING: A randomized, controlled study was performed. The patients were recruited from the Department of Anesthesia, Second Affiliated Hospital, Medical College, Xi'an Jiaotong University, China between May 2005 and December 2008. Genetic analyses were conducted at the Departments of Neuroanatomy and Forensic Medicine, Medical Corlege, Xi'an Jiaotong University, China. PARTICIPANTS: A total of t 000 patients of ASA I-II grade, without genetic connection, were enrolled in this study, comprising 520 males and 480 females, aged (70.1± 4.6) years and weighing (57.3 ± 7.5) kg. No patients suffered from cognitive dysfunction. METHODS: The patients were equally and randomly divided into intravenous anesthesia and gas anesthesia groups. Total intravenous anesthesia and inhaled anesthesia were used. Genomic DNA from whole blood was extracted. The ApoE gene was amplified by PCR. Restriction fragment length polymorphism of ApoE gene was analyzed. Cognitive function was evaluated by Mini-Mental State Examination (MMSE). Patients scoring 〈 25 points were diagnosed with cognitive dysfunction. MAIN OUTCOME MEASURES: Correlation of ApoE gene frequency and ApoE ε 4 allele to MMSE scores was measured. RESULTS: MMSE scores in patients from the gas anesthesia group significantly decreased 3 days after surgery, compared with the intravenous anesthesia group. The proportion of patients that scored 〈 25 points was significantly greater in the gas anesthesia group compared with the intravenous anesthesia group 3 days after surgery. Reduced MMSE scores closely correlated with expression of the ApoE ε 4 allele in the gas anesthesia group (odds ratio = 2.83; 95% confidence interval was 1.25-6.39, P 〈 0.05). However, decreased MMSE scores did not closely correlated with expression of the ApoE ε 4 allele in the intravenous anesthesia group (odds ratio = 0.96; 95% confidence interval was 0.37-2.39, P 〉 0.05). CONCLUSION: Results demonstrated a correlation between cognitive dysfunction and ApoE single nucleotide polymorphism in elderly patients after gas anesthesia. However, no relationship between cognitive dysfunction and ApoE single nucleotide polymorphism was determined in elderly patients following intravenous anesthesia. Therefore, elderly patients, especially those expressing the ApoE ε4 gene, should be cautiously exposed to gas anesthesia.展开更多
Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage cause...Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.展开更多
基金supported by the National Natural Science Foundation of China,No.81071070
文摘Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral ischemia/reperfusion injury rat model was established using a modified four-vessel occlusion method. Rats were treated with different doses of tea polyphenols (25, 50, 100, 150, 200 mg/kg) via intraperitoneal injection. Results showed that after 2, 6, 12, 24, 48 and 72 hours of reperfusion, peroxide dismutase activity and total antioxidant capacity in brain tissue gradually increased, while malondialdehyde content gradually decreased after tea polyphenol intervention. Tea polyphenols at 200 mg/kg resulted in the most apparent changes. Terminal deoxynucleotidyl transferase-mediated nick end labeling and flow cytometry showed that 200 mg/kg tea polyphenols significantly reduced the number and percentage of apoptotJc cells in the hippocampal CA1 region of rats after cerebral ischemia/reperfusion injury. The open field test and elevated plus maze experiments showed that tea polyphenols at 200 mg/kg strengthened exploratory behavior and reduced anxiety of cerebral ischemia/reperfusion injured rats. Experimental findings indicate that tea polyphenols protected rats against cerebral ischemia/ reperfusion injury and 200 mg/kg is regarded as the optimal dose.
基金Supported by: the National Natural Science Foundation of China, No. 30571790
文摘BACKGROUND: Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases (JNKs) signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE: To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi'an Jiaotong University from June 2007 to September 2008. MATERIALS: SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK (Thr183/Tyr185) polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 (XRCC1) and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS: A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group (I/R group) were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group (pre-SP group) was given 10 μL SP600125 (3 μg/μL). Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES: Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS: Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased (P 〈 0.01). Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased (P 〈 0.01). Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased (P 〈 0.05) following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group (P 〈 0.05). Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region (r = -0.983, -0.953, P 〈 0.01). CONCLUSION: SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.
基金Supported by:the Doctoral Special Foundation of Scientific Research in Universities,No. 20030698011the National Natural Science Foundation of China,No.30300395+1 种基金the National Natural Science Foundation of China,No.30400515the Tackle Key Program in Science and Technology of Shaanxi Province.No.2005K13-G2
文摘BACKGROUND: Cognitive dysfunction occurs in elderly patients following general anesthesia, and this might be associated with genetics. Studies have shown that the ε4 allele gene is closely associated with senile dementia. OBJECTIVE: To compare and analyze the correlations between cognitive dysfunction and single nucleotide polymorphism of apolipoprotein E (ApoE) following inhalation or intravenous anesthesia. DESIGN, TIME AND SETTING: A randomized, controlled study was performed. The patients were recruited from the Department of Anesthesia, Second Affiliated Hospital, Medical College, Xi'an Jiaotong University, China between May 2005 and December 2008. Genetic analyses were conducted at the Departments of Neuroanatomy and Forensic Medicine, Medical Corlege, Xi'an Jiaotong University, China. PARTICIPANTS: A total of t 000 patients of ASA I-II grade, without genetic connection, were enrolled in this study, comprising 520 males and 480 females, aged (70.1± 4.6) years and weighing (57.3 ± 7.5) kg. No patients suffered from cognitive dysfunction. METHODS: The patients were equally and randomly divided into intravenous anesthesia and gas anesthesia groups. Total intravenous anesthesia and inhaled anesthesia were used. Genomic DNA from whole blood was extracted. The ApoE gene was amplified by PCR. Restriction fragment length polymorphism of ApoE gene was analyzed. Cognitive function was evaluated by Mini-Mental State Examination (MMSE). Patients scoring 〈 25 points were diagnosed with cognitive dysfunction. MAIN OUTCOME MEASURES: Correlation of ApoE gene frequency and ApoE ε 4 allele to MMSE scores was measured. RESULTS: MMSE scores in patients from the gas anesthesia group significantly decreased 3 days after surgery, compared with the intravenous anesthesia group. The proportion of patients that scored 〈 25 points was significantly greater in the gas anesthesia group compared with the intravenous anesthesia group 3 days after surgery. Reduced MMSE scores closely correlated with expression of the ApoE ε 4 allele in the gas anesthesia group (odds ratio = 2.83; 95% confidence interval was 1.25-6.39, P 〈 0.05). However, decreased MMSE scores did not closely correlated with expression of the ApoE ε 4 allele in the intravenous anesthesia group (odds ratio = 0.96; 95% confidence interval was 0.37-2.39, P 〉 0.05). CONCLUSION: Results demonstrated a correlation between cognitive dysfunction and ApoE single nucleotide polymorphism in elderly patients after gas anesthesia. However, no relationship between cognitive dysfunction and ApoE single nucleotide polymorphism was determined in elderly patients following intravenous anesthesia. Therefore, elderly patients, especially those expressing the ApoE ε4 gene, should be cautiously exposed to gas anesthesia.
基金supported by the National Natural Science Foundation of China, No. 30571790
文摘Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.