Cardiomyocyte apoptosis and death receptor pathway in a rat model of coronary microembolization / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of cardiomyocyte apoptosis and the role of death receptor apoptotic pathway in a rat model of coronary microembolization (CME).</p><p><b>METHODS</b>Adult rats were randomized to coronary microembolization (CME group, n = 63) or sham-operated group (S group, n = 55). CME model was established by aortic injection of 0.1 ml microspheres (42 microm, 3 x 10(4)/ml) into the left ventricle when the ascending aorta was temporarily clamped.S group received 0.1 ml saline injection and survived rats were randomly examined at 0, 3, 6, 12 and 24 hour post CME (n = 10 each). Heart function was evaluated by echocardiography. Myocardium sample was stained with hematoxylin-eosin and hematoxylin-basic fuchsin-picric acid to detect infarct areas. Cardiomyocyte apoptosis was detected with TUNEL staining. The expression of caspase-3 and caspase-8 was measured by Western blot analysis.</p><p><b>RESULTS</b>Compared with S group, the left ventricular ejection fraction was significantly decreased and left ventricular end-diastolic diameter was significantly increased in CME group (all P < 0.05) except 0 hour CME group. The infarct sizes were similar in 3 hour, 6 hour, 12 hour, and 24 hour CME groups (P > 0.05). The apoptosis index (AI) in CME group were significantly higher at each time point compared to S group (P < 0.05) except 0 hour CME group and peaked at 6 hours. Apoptotic cardiomyocytes were found mainly in the myocardial microinfarcted area and border zones. The relative expression of caspase-3 and caspase-8 in CME group were both significantly increased at 3 hours and peaked at 6 hour post CME (P < 0.05).</p><p><b>CONCLUSION</b>Cardiomyocytes apoptosis was significantly increased after coronary microembolization via activating death receptor apoptotic pathway in this coronary microembolization model.</p>

Association between myocardial calpain activation and apoptosis in lipopolysaccharide-induced septic mouse model / 中华心血管病杂志

<p><b>OBJECTIVE</b>in septic mice, myocardial calpain was activated and induced caspase-3 activation, the association between calpain activation and apoptosis was explored in this experiment.</p><p><b>METHODS</b>in in vivo model, adult C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Myocardial calpain and caspase-3 activities, protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were detected by Western blot analysis and myocardial apoptosis was detected by TUNEL, myocardiac function was evaluated by Langendorff system. In in vitro model, adult rat cardiomyocytes were incubated with LPS (1 microg/ml) or co-incubated with calpain inhibitor-III (10 micromol/L), calpain activity, caspase-3 activity, protein levels of Bcl-2 and Bid, and cardiomyocyte apoptosis were detected.</p><p><b>RESULTS</b>in septic mice, myocardial calpain and caspase-3 activity were increased up to 2.7- and 1.8-folds, respectively. Both calpain inhibitor-III and PD150606 significantly attenuated the increase of caspase-3 activity. Myocardial protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were similar between control and septic mice, and no cleavage of both Bcl-2 and Bid was found in septic mice. Calpain inhibitor-III significantly improved myocardial function in septic mice. In in vitro model, calpain and caspase-3 activities were increased after 4 h LPS treatment, co-treatment with calpain inhibitor-III prevented caspase-3 activity increase, protein Bcl-2 and Bid were similar between normal cardiomyocytes and LPS-treated cardiomyocytes. Cardiomyocyte apoptosis was similar in in vivo and in vitro septic models.</p><p><b>CONCLUSION</b>myocardial calpain activity is increased in LPS induced septic mice, subsequent caspase-3 activation may contribute to myocardial dysfunction in septic mice without aggravating myocardial apoptosis and Bcl-2 and Bid are not involved on calpain induced caspase-3 activation in our model.</p>

Association between GATA-4 mutations and congenital cardiac septal defects in Han Chinese patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To elucidate the association between GATA-4 gene mutations and congenital cardiac septal defects in Han Chinese patients.</p><p><b>METHODS</b>Fifty Han Chinese patients with congenital cardiac septal defects and 100 normal subjects with the same ethnical background were studied. Total six exons and the intron-exon boundaries of GATA-4 were amplified by the polymerase chain reaction. The polymerase chain reaction products were purified and directly sequenced with automatic sequencer.</p><p><b>RESULTS</b>Two novel heterozygous mutations were discovered in the GATA-4 gene of patients with congenital cardiac septal defects, His28Tyr in exon 2 and His436Tyr in exon 7 respectively, which were absent in the control population and not reported in the SNP database (http://www.ncbi.nlm.nih.gov/SNP).</p><p><b>CONCLUSION</b>Our finding suggests that the mutations in the transcription factor GATA-4 may be related to congenital cardiac septal defects in Han Chinese patients.</p>

Preliminary functional analysis of a novel mutation in GATA-4 gene in Chinese patients with congenital cardiac septal defects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform the functional analysis of a novel H436Y mutation of GATA-4 gene identified in Han Chinese patients with congenital cardiac septal defects.</p><p><b>METHODS</b>Using bioinformatics to predict if the H436Y mutation in the GATA-4 gene affects its protein function. H436Y mutation in the GATA-4 gene was generated by Quick Change Lightning site-directed mutagenesis kit and verified by DNA sequencing. GATA-4-wt or GATA-4-mut DNA was cotransfected into Hela cells with DNA for the luciferase reporter gene atrial natriuretic factor (ANF), and luciferase activity was measured by an LKB luminometer 48 h after transient transfection.</p><p><b>RESULTS</b>Alignment of the GATA-4 amino acid sequence indicated that the histidine residue at position 436 was conserved, and H436Y mutation in the GATA-4 gene is expected to affect its protein function. The H436Y mutation significantly reduced the transcriptional activation of downstream reporter ANF when compared to wild-type GATA-4 (P<0.01).</p><p><b>CONCLUSION</b>The mutation c.1306C-->T of the GATA-4 gene impaired the activation of the downstream target, suggesting that the H436Y mutation in the C-terminal region of the GATA-4 gene might prevent its biological function.</p>

Effects of Astragalus injection in reversing left ventricular hypertrophy induced by renal hypertension in rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore whether the Astragalus injection (AI) has effect for reversing left ventricular hypertrophy and myocardial fibrosis induced by renal vascular hypertension in rats.</p><p><b>METHODS</b>Thirty male SD rats were randomized equally into three groups: the AI group, the control group and the sham-operated group. All rats, except those in the sham-operated group, were established into the hypertension models by two kidney one clip (2K1C) operation. Blood pressure was measured before operation and every 4 weeks after operation. AI intervention was given to rats in the AI group starting from the 4th week of experiment at dose of 8 g/kg by peritoneal injecting once a day for 8 weeks, while for rats in the other 2 groups, equal volume of normal saline was given instead. All rats were sacrificed 12 weeks after operation by cervical breaking. And indexes including left ventricular mass index (LVMI), left ventricular wall thickness (LVWT), inter-ventricular septal thickness (IVST), left ventricular diameter (LVD), cardiomyocytes diameter (CCD), collagen volume fraction (CVF), and peri-vascular volume collagen area (PVCA) in rats were measured.</p><p><b>RESULTS</b>Blood pressure was not different in the three groups before operation (P>0.05), whereas it rose in the control group and the AI group 4, 8 and 12 weeks after operation correspondingly, showing no difference between the two groups, but significantly higher than that in the sham-operated group (P<0.05). The related indexes in the sham-operated group, control group and AI group were: LVMI, 2.71 +/- 0.24, 3.42 +/- 0.26, 3.13 +/- 0.23, respectively; LVWT (mm), 2.25 +/- 0.42, 4.26 +/- 0.48, 3.28 +/- 0.36; IVST (mm), 2.13 +/- 0.38, 3.98 +/- 0.32, 3.02 +/- 0.28; and LVD (mm), 3.76 +/- 0.29, 2.18 +/- 0.27, 2.82 +/- 0.20 respectively. Comparisons showed that LVMI, LVWT and IVST were significantly higher, but LVD was significantly lower in the control group than those in the sham-operated group (P<0.05); LVMI, LVWT and IVST were significantly lower but LVD was significantly higher in the AI group than those in the control group (P<0.05). CCD, CVF and PVCA in the three groups (in the fore-mentioned order) were: CCD (microm), 14.54 +/- 2.25, 19.56 +/- 2.53, 16.58 +/- 2.46; CVF(%), 3.83 +/- 1.40, 11.21 +/- 2.96, 7.83 +/- 1.67; PVCA (%), 15.71 +/- 3.85, 30.58 +/- 6.25, 21.76 +/- 4.36, respectively. These indexes showed that CCD, CVF, PVCA in the control group were significantly higher than those in the sham-operated group (P<0.05); and those were significantly lower in the AI group than in the control group (P<0.05).</p><p><b>CONCLUSION</b>AI intervention can reverse the left ventricular hypertrophy and myocardial fibrosis induced by renal vascular hypertension in rats.</p>

Expression of Vascular Endothelial Growth Factor in Pulmonary Tissue of Newborn Rats with Pulmonary Hemorrhage / 实用儿科临床杂志

950 mL/L for 2 hours.Gross anatomical changes and histological changes(HE staining)of lungs were observed,VEGF expression was detected by immunohistochemical method.Results Two rats in hypothermia-hypoxia group and 4 rats in rewarming-reoxygenating group died while none in control group.Lungs of hypothermia-hypoxia group and rewarming-reoxygenating group represented edema and punctiform,local and diffuse pulmonary hemorrahge.Histopathological changes included pulmonary edema,alveolar septum broken,pulmonary alveoli fusion and pulmonary hemorrahge.More severe pathological change could be found in rewarming-reoxygenating group.Optical density value of VEGF expression in 3 groups were 0.29?0.06,0.36?0.05,0.22?0.05,respectively,there were significant diffe-rences of VEGF expression between 3 groups(F=15.64 P

Survey on blood pressure and serum lipids in Hei Yi Zhuang Chinese living in Guangxi / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the levels of blood pressure and serum lipids, and examine the relationship between hypertension and hyperlipidemia in Hei Yi Zhuang Chinese living in Guangxi.</p><p><b>METHODS</b>A total of 1056 people of Hei Yi Zhuang ethnicity were studied. Blood pressure, body height, body weight, and serum levels of lipids and apolipoprotein were measured. The data were compared with those in 925 people of Han ethnicity, who live in the same region.</p><p><b>RESULTS</b>Systolic blood pressure and pulse pressure were significantly higher in Hei Yi Zhuang than Han Chinese (P < 0.001). The prevalence of isolated systolic hypertension and hypertension was also significantly higher in Hei Yi Zhuang than Han Chinese (P < 0.001). Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein (Apo) B, and the prevalence of hypercholesterolemia and hyperlipidemia were significantly lower in Hei Yi Zhuang than Han Chinese (P < 0.05). Serum concentrations of high-density lipoprotein cholesterol and the Apo A1 to Apo B ratio were significantly higher in Hei Yi Zhuang than Han Chinese (P < 0.001). The prevalence of hypertension in Hei Yi Zhuang Chinese was positively associated with triglycerides (r = 0.425, P < 0.05), whereas the prevalence of hypertension in Han Chinese was positively correlated with total cholesterol (r = 0.623, P < 0.001).</p><p><b>CONCLUSION</b>The present study revealed a significant difference in blood pressure and serum lipids between Hei Yi Zhuang and Han ethnic groups, and an association between hypertension and hyperlipidemia.</p>

Expression and Role of Vascular Endothelial Growth Factor in Pulmonary Tissue of Newborn Rats with Pulmonary Hemorrhage / 实用儿科临床杂志

95 mL/L O2) for 2 hours.The gross anatomical and histological changes(HE staining)in lungs were observed,VEGF mRNA expressions were studied by reverse transcription polymerase chain reaction(RT-PCR).Results Lungs of experimental groups represented edema,inaddition,punctiform,local and diffuse pulmonary hemorrhage were observed in groups of HH,HHR and HHRO2.Histopathological changes included pulmonary alveoli and interstitial edema,spacer breaking,pulmonary alveolidilating,fusion and hemorrhage,in which the most severe cases involved in group HHRO2.VEGF 188 mRNA expression increased significantly in group H and HH(P