OBJECTIVE: We aimed to evaluate the combined effects of a high body shape index (ABSI) and a high serum C-reactive protein (CRP) level on the incidence of ischemic stroke in a Mongolian population in China. METHODS: A prospective cohort study was conducted among 2,589 participants from June 2002 to July 2012 in Inner Mongolia, China. The participants were categorized into 4 groups according to their level of ABSI and CRP. Cox proportional hazards models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for ischemic stroke among all groups. RESULTS: The multivariate adjusted HRs (95% CI) of ischemic stroke for high ABSI and high CRP level were 1.46 (0.89-2.39) and 1.63 (0.95-2.79), respectively. Compared with the low ABSI/low CRP level group, the multivariate adjusted HRs (95% CI) of ischemic stroke in the low ABSI/high CRP, high ABSI/low CRP, and high ABSI/high CRP groups were 1.04 (0.46-2.35), 1.06 (0.58-1.95) and 2.52 (1.27-5.00), respectively. The HR of ischemic stroke for the high ABSI/high CRP level group was the highest and most statistically significant. CONCLUSION We found that participants with simultaneously high ABSI and high CRP levels had the highest risk of ischemic stroke in the Mongolian population. Our findings suggest that the combination of high ABSI and high CRP levels may increase the risk of ischemic stroke.
Adult ; Aged ; Anthropometry ; Brain Ischemia ; epidemiology ; etiology ; C-Reactive Protein ; metabolism ; China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Mongolia ; ethnology ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Stroke ; epidemiology ; etiology

Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia (ACI), we established a middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor β (GMFB) based on quantitative analysis of the global rat serum proteome. Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was over-expressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation (OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium (CM) after OGD. We then used the CM to culture pulmonary microvascular endothelial cells (PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover, ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells. In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.
Animals ; Brain ; metabolism ; pathology ; Brain Ischemia ; complications ; pathology ; Bronchoalveolar Lavage Fluid ; Cell Hypoxia ; physiology ; Cells, Cultured ; Cerebrovascular Circulation ; physiology ; Chromatography, High Pressure Liquid ; Culture Media, Conditioned ; pharmacology ; Disease Models, Animal ; Endothelial Cells ; metabolism ; Gene Expression Regulation ; physiology ; Glia Maturation Factor ; metabolism ; In Situ Nick-End Labeling ; Lung Injury ; etiology ; metabolism ; pathology ; Male ; Neuroglia ; metabolism ; Neurologic Examination ; Peroxidase ; metabolism ; Proteome ; RNA Interference ; physiology ; RNA, Small Interfering ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Tandem Mass Spectrometry

The aim of this study was to investigate whether the omega-3 fatty acids help to improve erectile function in an atherosclerosis-induced erectile dysfunction rat model. A total of 20 male Sprague-Dawley rats at age 8 weeks were divided into three groups: Control group (n = 6, untreated sham operated rats), Pathologic group (n = 7, untreated rats with chronic pelvic ischemia [CPI]), and Treatment group (n = 7, CPI rats treated with omega-3 fatty acids). For the in vivo study, electrical stimulation of the cavernosal nerve was performed and erectile function was measured in all groups. Immunohistochemical antibody staining was performed for transforming growth factor beta-1 (TGF-β1), endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor 1-alpha (HIF-1α). In vivo measurement of erectile function in the Pathologic group showed significantly lower values than those in the Control group, whereas the Treatment group showed significantly improved values in comparison with those in the Pathologic group. The results of western blot analysis revealed that systemically administered omega-3 fatty acids ameliorated the cavernosal molecular environment. Our study suggests that omega-3 fatty acids improve intracavernosal pressure and have a beneficial role against pathophysiological consequences such as fibrosis or hypoxic damage on a CPI rat model, which represents a structural erectile dysfunction model.
Animals ; Atherosclerosis/*complications ; Blotting, Western ; Carotid Arteries/physiology ; Chronic Disease ; Disease Models, Animal ; Electric Stimulation ; Fatty Acids, Omega-3/*pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Ischemia/etiology/*pathology ; Male ; Nitric Oxide Synthase Type III/metabolism ; Penile Erection/*drug effects ; Penis/metabolism/pathology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism

OBJECTIVETo assess the association of a disintegrin and metallo-proteinase with thrombospondin type 1 motifs (ADAMTS-1) gene polymorphism and ischemic stroke caused by large artery atherosclerosis (LAA).

METHODSIn total 767 patients and 506 controls were recruited. Single nucleotide polymorphisms (SNPs) rs416905 (T/C) and rs402007 (G/C) of the ADAMTS-1 gene were genotyped by polymerase chain reaction and DNA sequencing.

RESULTSFrequencies of the rs402007 GC+CC genotype and the C allele were significantly different between the two groups (68.84% vs. 60.67%, χ2=9.012, P=0.003, OR=1.432; 45.24% vs. 38.54%, χ2=11.208, P=0.001, OR=1.318). Binary logistic regression has confirmed that the above difference was significant (P=0.001, OR=1.521, 95%CI: 1.183-1.955). The frequencies of TC+CC and GC+CC genotypes were similar between the two groups, and so was it with the C allele. The two SNPs had been in complete linkage disequilibrium (D'=1.0, r2=1.0).

CONCLUSIONThe rs416905 and rs402007 polymorphisms of the ADAMTS-1 gene may be associated with ischemic stroke caused by LAA. The C allele of the rs402007 locus may be a susceptibility factor for this subtype of stroke.

ADAM Proteins ; genetics ; ADAMTS1 Protein ; Aged ; Alleles ; Atherosclerosis ; complications ; Base Sequence ; Blood Glucose ; metabolism ; Brain Ischemia ; complications ; Fasting ; blood ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Risk Factors ; Sequence Analysis, DNA ; Smoking ; Stroke ; blood ; etiology ; genetics

To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Creatine Kinase ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Humans ; Ischemia ; drug therapy ; etiology ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; etiology ; metabolism ; physiopathology ; Myocardium ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

This study aimed to investigate inflammatory edema after cerebral ischemia through 7.0T MRI and proton magnetic resonance spectroscopy (MRS). All SD rats were randomly divided into sham operated group and middle cerebral artery occlusion (MCAO)-1 day, -3 day and -7 day groups. MRI scan of the brain was performed on a 7.0 Tesla MRI scanner. The volume of positive signals in the ischemic side was detected by using a T2 weighted spinecho multislice sequence; the changes in the height of water-peak were measured with point resolved spectroscopy (PRESS) sequences; cortical edema was detected by using wet-dry weight method; the degrees of nerve injury were evaluated by Bederson neurological score system; double-labeling immunofluorescence technique was used to explore the molecular mechanisms of post-ischemia cerebral edema. The results showed that high T2WI signals were observed in MCAO-1 day, -3 day and -7 day groups, and the water-peak height and water-peak area of MCAO groups were higher than those of sham operated group (P<0.05). Neurological score results were consistent with the degree of brain edema, and a large number of microglia accumulated in the ischemic cortex. Our results suggested that non-invasive MRI technology with the advantage of high spatial resolution and tissue resolution can comprehensively and dynamically observe inflammatory edema after cerebral ischemia from a three-dimensional space, and contribute to evaluation and treatments in clinic.
Animals ; Brain ; diagnostic imaging ; pathology ; Brain Edema ; diagnostic imaging ; etiology ; Brain Ischemia ; complications ; CD11b Antigen ; metabolism ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; complications ; Inflammation ; diagnostic imaging ; etiology ; Magnetic Resonance Imaging ; methods ; Magnetic Resonance Spectroscopy ; Male ; Microglia ; metabolism ; Microscopy, Confocal ; Microscopy, Fluorescence ; Radiography ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Time Factors

OBJECTIVETo investigate the protective effects of Jiedu Tongluo injection on cerebral edema induced by focal lesion of cerebral ischemia/reperfusion, the hydrous content of brain and the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and MMP-9 in rats.

METHODThe model of brain middle cerebral artery ischemia/reperfusion was established by the thread approach. After 24 hours of reperfusion, cerebral edema formation was determined by the hydrous content of brain. The permeability of blood brain barrier was evaluated based on the leakage of Evans blue. Enzyme-linked immunoadsordent assay (ELISA)was used to examine the expression of ICAM-1, VCAM-1, E-selectin. The expression of MMP-9 was measured by immunohistochemistry.

RESULTJDTL, in the dose of 2 mL x kg(-1) and 4 mL x kg(-1), relieved cerebral edema (P < 0.05, P < 0.01), reduced the expressions of ICAM-1, VCAM-land E-selectin and decreased MMP-9 activity (P < 0. 05, P < 0.01) in model rats.

CONCLUSIONJiedu Tongluo injection has a protective effect on rat brain from cerebral edema induced by the injury of focal cerebral ischemia/reperfusion. The mechanism is related to that Jiedu Tongluo injection can reduce the expressions of ICAM-1, VCAM-1 and E-selectin and inhibit of MMP-9 activation in rat brain.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Edema ; etiology ; metabolism ; prevention & control ; Brain Ischemia ; complications ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; E-Selectin ; metabolism ; Evans Blue ; metabolism ; Gene Expression Regulation, Enzymologic ; drug effects ; Injections ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Permeability ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; Vascular Cell Adhesion Molecule-1 ; metabolism

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; Drug Synergism ; Gene Regulatory Networks ; drug effects ; genetics ; Iridoids ; pharmacology ; Linear Models ; Male ; Mice ; Models, Genetic ; Oligonucleotide Array Sequence Analysis ; Reperfusion Injury ; drug therapy ; etiology ; genetics ; Signal Transduction ; drug effects ; genetics ; Transcriptome ; drug effects ; genetics ; Ursodeoxycholic Acid ; pharmacology

OBJECTIVETo study the effects of biological clock protein on circadian disorders in hypoxic-ischemic brain damage (HIBD) by examining levels of CLOCK and BMAL1 proteins in the pineal gland of neonatal rats.

METHODSSeventy-two 7-day-old Sprague-Dawley (SD) rats were randomly divided into sham-operated and HIBD groups. HIBD model was prepared according to the modified Levine method. Western blot analysis was used to measure the levels of CLOCK and BMAL1 in the pineal gland at 0, 2, 12, 24, 36 and 48 hours after operation.

RESULTSBoth CLOCK and BMAL levels in the pineal gland increased significantly 48 hours after HIBD compared with the sham-operated group (P<0.05). There were no significant differences in levels of CLOCK and BMAL proteins between the two groups at 0, 2, 12, 24 and 36 hours after operation (P>0.05).

CONCLUSIONSLevels of CLOCK and BMAL1 proteins in the pineal gland of rats increase significantly 48 hours after HIBD, suggesting that both CLOCK and BMAL1 may be involved the regulatory mechanism of circadian disorders in rats with HIBD.

ARNTL Transcription Factors ; analysis ; physiology ; Animals ; Animals, Newborn ; CLOCK Proteins ; analysis ; physiology ; Chronobiology Disorders ; etiology ; Female ; Hypoxia-Ischemia, Brain ; metabolism ; Male ; Pineal Gland ; chemistry ; Rats ; Rats, Sprague-Dawley ; Time Factors

OBJECTIVETo inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis (2-DE) map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome.

METHODSAmeroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome.

RESULTSThe preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDITOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 (NAD+) alpha, NADH dehydrogenase (NAD) Fe-S protein 1, chain A (crystal structure of aldose reductase by binding domain reveals a new Nadph), heat shock protein 27 (HSP27), oxidoreductase (NAD-binding protein), antioxidant protein isoform, cardiac troponin T (cTnT), myosin (myosin light polypeptide), cardiac alpha tropomyosin, apolipoprotein A-I and albumin.

CONCLUSIONDown-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker(s) for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine.

Animals ; Blood Coagulation Disorders ; complications ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; physiology ; Metabolic Diseases ; etiology ; metabolism ; Myocardial Ischemia ; complications ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Proteomics ; methods ; Qi ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Swine ; Swine, Miniature ; Syndrome