Objective To investigate the role of apoptosis and apoptotic proteins p53,p21 and Bax in mechanisms of brain ischemic tolerance in rats.Methods In our study the models of focal-focal type brain ischemic preconditioning were maded by occlusion middle cerebral artery using an intraluminal filament method. Infarct sizes were measured by image analysis system.Neuronal apoptosis was identified by TUNEL staining and expressions of p53, p21 and Bax were analyzed by immunohistochemistry.Results Compared with the lethal ischemic group, the volume of infarct was greatly reduced when MCAO 20 minutes was performed as ischemic preconditioning( P

Objective To verify the efficacy and safety of Edaravone,a novel hydroxy-free radical scavenger,on acute cerebral infarction(ACI).Methods We performed a randomized,placebo-controlled,parallel-group,double-blind study on ACI patients. 63 patients,enrolled within 48h of onset,were allocated to Edaravone group( n = 31) or the placebo group( n = 32) randomly. Edaravone was infused at a dose of 30 mg,twice a day,for 14 days. Meanwhile,Hydroxyethylrutin and Aspirin were taken as basic treatment. The therapies of the placebo group were similar to those of Edaravone group except for Edaravone.Before treatment and at 7th,14th and 21th day after treatment,the neurological deficits and activities of daily living (ADL) were evaluated using European Stroke Scale (ESS) and Barthel Index respectively. 3 months later,all the patients were followed up for survival and ADL.Results At 21th day the increase rate of ESS was evaluted.There were significan difference between Edaravone group[(60.3?28.2)%] and the placebo group[( 35.1? 23.6)%]( P

Objective To explore the clinical characteristics of neuromyelitis optica(NMO).Methods The clinical data of 18 patients with NMO were analyzed retrospectively.Results Of the enrolled patients,15 cases(83.3%) were relapsing form of NMO,16 cases(88.9%) were female and the mean onset age was 36 years old.Simultaneous bilateral optic neuritis(ON) or ON occured sequentially and horizontal impairent of spinal cord were the main clinic features in these 18 patients.Of the patients who received spinal cord MRI examinations,4 cases showed the lesions located in cervical cord,6 cases in thoracic cord and 5 cases in both cervical and thoracic cord.13 cases revealed lesions in spinal cord extended across 3 or more vertebral segments.Furthermore,brain lesions were detected by MRI in 6 patients.The mean onset number of per patient was five.Seven patients presented with mild disability,7 patients with median disability,2 patients with severe disability and death of 2 patients.Conclusions Most patients with NMO are female and relapsing form accounts for the majority type.The cardinal manifestations are bilateral ON and longitudinally extensive transverse myelitis(LETM).Some patients show brain lesions that may be detected by MRI examination.Relatively high relapsing frequency of clinical event and severe impairing are common in NMO.

Objective To observe the expressions of apoptosis-related proteins Bcl-2 and Bax in cerebral ischemic preconditioning-perfusion models of rats. Methods Ischemic preconditioning was induced by 20 minutes of monolateral middle cerebral artery occlusion using an intraluminal filament method in rats. The animals were perfused 6 h, 12 h, 1d, 3 d, 5 d and 7 d respectively before they were sacrificed. The expressions of Bcl-2 and Bax were analyzed by immunohistochemistry staining. Results Bcl-2 positive cells increased significantly at 1 d after perfusion, reached their peak at 3 d, and maintained high level until 7 d. They were all higher than that of control group (all P 0.05). Conclusion Upregulation of Bcl-2 but not Bax may play a role in ischemic preconditioning protection .

AIM:Cytochrome P450 epoxygenase 2J2 and epoxyeicosatrienoic acids ( EETs) are known to protect against cardiac hypertrophy and heart failure, which involve activation of 5′-AMP-activated protein kinase ( AMPK) and Akt.Although the functional roles of AMPK and Akt are well established , the significance of crosstalk between them in the development of cardiac hypertrophy and anti -hy-pertrophy of CYP2J2 and EETs remains unclear .Here, we investigated whether CYP 2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1.Moreover, we tested whether EETs enhanced crosstalk between AMPKα2 and phosphorylated Akt1 ( p-Akt1), and stimulated the nuclear translocation of p-Akt1, to exert their anti-hypertrophic effects. METHODS:The recombinant rAAV9 vector was coupled to CYP2J2 and the rAAV9-CYP2J2 construct was injected into the caudal vein of AMPKα2-/-and littermate control mice .AMPKα2 -/-and littermate control mice that overexpressed CYP 2J2 in heart were treated with angiotensin II (Ang II) for 2 weeks.Hemodynamic and cardiac functions were also evaluated after 14 days of infusion with Ang II or saline.RESULTS:Interestingly, the overexpression of CYP2J2 suppressed cardiac hypertrophy , including decreased heart size, cross sectional area of cardiomyocytes , markers of cardiac hypertrophy [ brain natriuretic peptide ( BNP) ,β-myosin heavy chain (β-MHC) and skeletal muscle α-actin (ACTA1)] and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2 -/-mice.Measurement of left ventricular ejection fraction and fractional shortening showed that CYP2J2 overexpression prevented Ang II-induced ventricular systolic dysfunction in mice .Moreover, an Ang II-induced reduction in cardiac function, demonstrated by decreased dp/dtmax and dp/dtmin, was prevented by overexpression of CYP2J2.Mechanistically, the CYP2J2 metabolites 11,12-EET activated AMPKα2 to induce the nuclear translocation of p-Akt1, which increased production of ANP and thereby inhibited the development of cardiac hypertrophy .Furthermore , by co-immunoprecipitation analysis , we found that full-length Akt1 and an Akt1 fragment containing amino acids 150-408, which constitute the protein kinase domain , but not other frag-ments of Akt1, bind to the AMPKγ1 subunit.AMPKα2β2γ1 and p-Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain.This interaction was enhanced by 11,12-EET.CONCLUSION:Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hy-pertrophy and suggest that overexpression of CYP 2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure .

Objective To observe the effects of diammonium glycyrrhizinate (DG) on arrhythmia induced by acute myocardial ischemia-reperfusion injury.Methods Electrocardiogram of lead Ⅱwas examined on the myocardial ischemia-reperfusion model,which was induced by the 10 min of ligation of left descending coronary artery and then 30 min of reperfusion in rats.Myocardial malondialdehyde (MDA) content,superoxide dismutase (SOD) activity and adenosine triphosphatase (ATPase),and serum lactate dehydrogenase (LDH) and creatine phosphokinase (CK) levels were measured.Results As compared with the model,DG significantly reduced the incidence of ventricular arrhythmia and its score (P

AIM:The 50-Hz magnetic field (MF) is a potential health-risk factor.Its effects on the cardiovascular system have not been fully investigated .This study was conducted to explore the effects of long-term exposure to 50-Hz MF on the cardiovascular system . METHODS:In the study , an exposure system was constructed and the distribution of 50-Hz MF was detected .Sixty-four Sprague-Dawley (SD) rats were exposed to 50-Hz MF at 100 μT for 24 weeks, 20 hours per day, while another 64 rats were sham exposed. During the exposure, blood pressure was measured every 4 weeks, and 24 weeks later, echocardiography, cardiac catheterisation and electrocardiography were performed .Moreover , heart and body weight were recorded , while haematoxylin-eosin staining and real-time PCR were conducted .RESULTS:The results showed that compared with the sham group , exposure to 50-Hz MF did not exert any effect on blood pressure, pulse rate, heart rate and cardiac rhythm.Further, echocardiography and cardiac catheterisation showed that there were no significant differences in the cardiac morphology and haemodynamics .In addition , histopathological examination showed that 50-Hz MF exposure had no effect on the structure of hearts .Finally, the expression of the cardiac hypertrophic relative genes did not show any significant differences between 50-Hz MF exposure group and the sham group .CONCLUSION: Taken together , in SD rats, exposure to 50-Hz/100-μT MF for 24 weeks did not show any obvious effects on the cardiovascular system .

Objective To investigate the interference and associated mechanism of hnman tissue kallikrein (HK) gene on renal interstitial fibrosis in rats with 5/6 nephrectomy. Methods Human kallikrein cDNA was packed in a recombinant adeno-associated virus(rAAV)-based plasmid vector. The rAAV-HK was produced by transfection in 293 cells. Twenty-four male Wistsr rats were divided into sham operation and operation groups. The rats with 5/6 nephrectomy were randomly divided into simple operation, control and experiment groups. The rats in experiment group received single dose rAAV-HK via the tail vein with 1×1011 pfu. Before nephrectomy and every month after surgery until the rats were sacrificed, the caudal arterial pressure was measured using tail cuff blood pressure determinator. Three months after HK gene delivery, the rats were sacrificed. The expression of HK in rats was assessed by RT-PCR, Western blot and enzyme-linked immunosorbent assay (ELISA). The pathological changes of renal interstitium were evaluated by Masson stainning, and the distribution of bradykinin B2 receptor (BKB2R) and angiotensin Ⅱ typel receptor (ATIR) was examined by immunohistochemistry. The expressions of BKB2R, AT1R, p-MAPK protein in renal tissue were detected by Western blot. Results Three months after HK gene delivery, the systolic blood pressure of experiment group was significantly decreased compared with the control group [(163±13) nun Hg vs (217±16) mm Hg, P<0.01](1 mm Hg=0.133 kPa). Compared with sham rats, the rats in simple operation group and control group had much more renal interstitial collagen deposition and more serious fibrosis performance, but renal interstitial collagen deposition and fibrosis were significantly ameliorated in the rats of experiment group. In addition, the tubulointerstitial injury index of HK transgenic rats was significantly lower than that of the rats in control group (1.33±0.73 vs 3.01±0.62, P<0.01). Up-regnlating expression of bradykinn B2 receptor protein and down-regulating expression of AT1 receptor and p-MAPK protein were found in renal tissues of experimental group after three months (P<0.05). Conclusion HK gene delivery significantly alleviates renal interstitial fibrosis in rats with 5/6 nephrectomy through regulating the expression of bradykinin B2 receptor, AT1 receptor and p-MAPK in renal tissue.

This study examined the sodium nitroprusside (SNP) toxicity to central nervous system (CNS) in treatment of patients with aortic dissection (AD). The medical records of 191 AD patients who were admitted to Tongji Hospital, China, from Jan. 1998 to Feb. 2009 were retrospectively analyzed. There were 140 cases of hypertension (73.3%) and 13 cases of Marfan syndrome (6.8%) among the 191 AD patients. A total of 157 patients were given SNP treatment. The toxic reactions of CNS occurred in 18 subjects (11.5%). Most of the adverse reactions occurred on the fifth day following SNP injection. SNP infusion rate was significantly higher in patients who developed CNS toxicity. It was suggested that systemic hypertension is the most common predisposing factor for AD. The combination of SNP with a β-receptor blocker is a medical therapy commonly used in patients with AD. Cyanide and thiocyanate toxicity from SNP treatment is always the consequence of prolonged drug infusion or relatively high dose administration.

BACKGROUND:Cytochrome P450 ( CYP) epoxygenases metabolize arachidonic acids ( AA) to form epoxyeicosatrienoic acids
(EETs), which exert beneficial roles in the treatment of cardiovascular diseases , but little is known about its role on adventitial remo-deling.METHODS:We used C57BL/6J mice in vivo and primary rat adventitial fibroblasts ( AFs) in vitro treated with angiotensin II (Ang II) to investigate the effects of CYP2J2 gene delivery and exogenous EETs administration on adventitial remodeling .RESULTS:CYP/sEH system was found to exist in human adventitia , and involved in adventitial remodeling process .Exogenous EETs administra-tion significantly inhibited Ang II-induced AFs activation , characterized by differentiation , proliferation, migration, and collagen syn-thesis.These protective effects were partially reversed by PPARγantagonist GW9662 pretreatment or SOCS3 siRNA transfection.EETs suppressed Ang II-induced IκBαphosphorylation , subsequent NF-κB nuclear translocation via PPARγdependent signaling pathway in AFs.Additionally, EETs reduced Ang II-induced JAK2, STAT3 phosphorylation and subsequent phosphor-STAT3 nuclear transloca-tion, which were mediated by SOCS3 induction but independent of PPARγactivation.Furthermore, rAAV-CYP2J2 gene delivery re-duced vessel wall thickening , AFs differentiation , proliferation and collagen deposition in aortic adventitia induced by Ang II infusion , which were mediated by NF-κB and SOCS3/JAK/STAT signaling pathways in blood pressure-dependent and -independent manners , re-spectively.CONCLUSION:We concluded that CYP2J2 overexpression attenuated Ang II-induced adventitial remodeling via PPARγ-dependent NF-κB and PPARγ-independent SOCS 3/JAK/STAT inflammatory signaling pathways .