ABSTRACT
Aim Toresearchthemolecularmecha-nisms of adriamycin-induced cardiomyocyte apoptosis based on β-adrenoceptor signaling pathway during de-velopmentofheartfailure.Methods SeventymaleSD rats were assigned randomly into two groups:the con-trol group(CON,n=30)and the ADR-induced cardio-toxicity group (ADR,n =40 ).ADR was administered intraperitoneally in five equal injections (each contai-ning 3 mg·kg-1 )over a period of two weeks,with a total cumulative dose of 15 mg · kg-1 body weight. Age-matched rats injected with saline were used as controls.The general condition of all rats was observed, and transthoracic echocardiography was performed im-mediately following the final ADR injection,and then every other week.Serum and myocardial tissue were harvested at W2,W4 and W6 separately.The serum contents of brain natriuretic peptide(BNP)and cardiac troponin-T(cTn-T)were analyzed by euzymelinked im-munosorbent assay (ELISA ).The pathological change and apoptosis were determined by HE,Masson and ter-minal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL).The protein expressions ofβ1-AR,β2-AR,PKA and CaMK Ⅱ were detectedbyWesternblot.Results FollowingthefinalADRin-jection,cardiac systolic function and SV declined, which was accompanied by marked atrophy of the heart,low levels of cardiomyocyte fibrosis and apopto-sis,significantly increased serum BNP and cTn-T and decreased β1-AR,PKA and CaMK Ⅱ protein expres-sion.However,cardiac systolic function was improved with the extension of time but remained depressed as compared to CON group.The serum BNP and cTn-T concentration kept on rising.The gradual aggravation apoptosis and concomitant fibrosis in the ADR group heart were observed following ADR withdrawal.β1-AR protein expression was continuously down-regulated,β2-AR protein expression unchanged.Expression of PKA and CaMKⅡ proteins in hearts from ADR-injec-ted rats gradually increased.Conclusion β-AR/PKA/CaMKⅡ signaling pathway mediates cardiomyo-cyte apoptosis during the progress of ADR-induced car-diac dysfunction and pathological remodeling and apop-tosis.
ABSTRACT
Objective To investigate the expression of AIF, CYT C, PAF-1, caspase-3, and XIAP in Sprague-Dawley rats with spontaneous mammary neoplasms.Methods One-hundred and thirty 3-4-week old SPF Spargue-Dawley rats (♀∶♂=1∶1) were fed in a specific pathogen free (SPF) breeding barrier for 60 weeks.The occurrence of spontane-ous breast tumors was recorded and histopathology was performed to identify the types of tumors.The rats were divided into 3 groups:rats with normal breast tissue ( group I) , with benign tumors ( group II) and with malignant tumors ( group III) . The expression of AIF, CYT C, APAF-1, caspase-3 and XIAP proteins and mRNAs were detected by immunhistochemistry ( IHC) and RT-PCR assay.Results Among these 130 SD rats, 14 rats were observed having spontaneous mammary neo-plasms with the incidence rate of 10.77%(14/130).In these neoplasm cases, 7 cases were mammary fibroadenomas, 7 cases of breast carcinoma, both with an incidence rate of 5.38%.Immunohistochemistry showed that, compared with the group I, the positive expressions of AIF, APAF-1, caspase-3 were decreased significantly (P<0.01), and the CYT C and XIAP expressions were significantly increased in the group II.The positive expression of all genes except XIAP was de-creased in the group III(P<0.01).Compared with the group II, APAF-1 and XIAP were significantly higher in the group III (P<0.01), and the positive expression of AIF, Cyt C, and caspases-3 were significantly decreased (P<0.01).In the results of RT-PCR assay, except APAF-1 which showed significant correlation with the results of immunohistochemistry ( P<0.05 ) , all the others showed an extremely significant correlation with immunohistochemical results ( P <0.01 ) . Conclusions Mammary tumors are most common spontaneous neoplasms in SD rats.Abnormal expression of mitochondrial apoptotic pathway-related factors AIF, CytC, APAF-1, caspase-3, and XIAP are correlated with the carcinogenesis and de-velopment of breast tumors.
ABSTRACT
Aim To optimize the traditional method of right catheterization in rats and establish a rapid , stable and reliable method of the right heart catheter guided intubation to measure pulmonary artery pressure. Methods Nighty male wistar rats were used to optimize the method of detection of pulmonary arte-rial pressure. Three catheter namely PE50, PU I, and PU II were used for choosing the best intubation. The new technology of right catheterization was established and used for the research of pulmonary arterial hypertension. Results The PU I catheter was obviously better than PE50 and PU II catheter in the success rate and measurement time ( P <0. 05 ) . The method of right heart catheter guided intubation was significantly superior to the traditional right heart direct intubation (P<0. 05 or P<0. 01). After improving the right catheterization, the detection of hemo-dynamic indexes in PAH-model rat was successful with regular pressure curve and reliable experimental data. Conclusions The right heart catheter guided intubation method has a high suc-cess rate and it can detect the pulmonary artery pressure quick-ly, easily, and can help other researchers to complete experi-ment as efficiently as possible.
ABSTRACT
Capsular warning syndrome (CWS) is a subtype of recurrent stereotyped transient ischemic attacks that heralds a subsequent stroke.The mainly presumed mechanism is repeated bursts of ischemia in the region of penetrating arteries,since the structural changes of large arteries is rare in series of imaging examinations.The majority of the infarct is located in the internal capsule or pontine.CWS is usually therapeutically resistant to simple traditional antithrombotic treatment,while combined antiplatelet treatment,thrombolysis,endovascular intervention and antiepileptics may protect part of the patients from developing into permanent infarcts.