Angiotensin II increases ROS production in cardiac fibroblasts by inducing p22phox over-expression / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in the reactive oxygen species (ROS) in rat cardiac fibroblasts exposed to angiotensin II (Ang II) treatment and explore the possible pathways that mediate ROS production.</p><p><b>METHODS</b>In vitro cultured fetal rat cardiac fibroblasts treated with apocynin (APO, 100 micromol/L), Ang II (10(-7) mol/L), or APO+Ang II (10(-7) mol/L Ang II was added 1 h after 100 micromol/L APO), and the ROS levels and p22phox expression in the cells were detected using fluorescent microscope and immunohistochemistry, respectively.</p><p><b>RESULTS</b>Compared with the normal control cells, Ang II treatment of the cardiac fibroblasts resulted in significantly increased ROS production, the effect of which was inhibited by the application of APO. p22phox expression was hardly detected by immunohistochemistry in the control cells, but over-expressed in AngII-treated cells. APO substantially decreased the over-expression of p22phox induced by Ang II.</p><p><b>CONCLUSION</b>Ang II increases ROS production in fetal rat cardiac fibroblasts probably by inducing p22phox over-expression.</p>

Effects of selenium and/or iodine deficiency on chondrocyte apoptosis in rats / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of selenium and/or iodine deficiency on chondrocyte apoptosis in articular cartilage in rats.</p><p><b>METHODS</b>Forty-eight Sprague-Dawley rats were randomly divided into selenium deficiency group, iodine deficiency group, combined selenium and iodine deficiency group, and control group. Chondrocyte apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and Bcl-2 and Bax in articular cartilage were stained by immunohistochemistry in F3 generation of rats.</p><p><b>RESULTS</b>In articular cartilage, the positive rate of apoptotic chondrocytes stained by TUNEL in the upper and middle zones in selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05) were significantly higher than that in control group. The apoptotic chondrocytes were prominent in the middle zone. The positive percentage of chondrocytes apoptosis was not significantly different among these three groups (P > 0.05). Compared with the control group, the expressions of both Bcl-2 and Bax were significantly higher in the upper and middle zone in the selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05); however, the expressions of Bcl-2 and Bax were not significantly different among these three groups (P > 0.05).</p><p><b>CONCLUSION</b>Selenium and/or iodine deficiency may induce chondrocyte apoptosis.</p>

Angiotensin II type 2 receptors participate in the regulation of inflammatory cytokine secretion in adult rat hypertrophied cardiomyocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of angiotensin II (AngII) type 2 (AT2) receptors on pressure overload-induced inflammatory cytokine secretion in adult rat hypertrophied cadiomyocytes.</p><p><b>METHODS</b>Rat models of left ventricular hypertrophy induced by pressure overload was established by placing a band around the abdominal aortic of the rats, from which the hypertrophied cadiomyocytes were isolated and purified 8 weeks later. The isolated cardiomyocytes were treated with AngII plus losartan or AngII plus PD123319, and 36 h after the treatments, the expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in the supernatant were detected using radioimmunoassay.</p><p><b>RESULTS</b>AngII induced TNF-alpha and IL-1beta secretion from the hypertrophied cardiomyocyets, and pretreatment of the cells with PD123319, but not losartan, decreased their secretion. IL-6 level was not detected in the supernatant.</p><p><b>CONCLUSION</b>AngII-induced the expression of inflammatory cytokines in adult rat hypertrophied cardiomyocytes is mediated mainly by AT2, not by AT1 receptors.</p>

Epimedium alleviates chemotherapy-induced damage to the ultrastructure and function of rat epididymides / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the protective action of Epimedium against chemotherapy-induced damage to rat epididymides.</p><p><b>METHODS</b>Fifty 60-day-old male rats were divided into a control, a model and a treatment group. Procarbazine was injected into the abdominal cavity of the model rats at the dose of 30 mg/(kg x d). In addition to procarbazine, Epimedium was given intragastrically to the treatment group. The changes in the ultrastructure of the epididymis were observed after 10 and 20 days.</p><p><b>RESULTS</b>Electron microscopy showed that the chemotherapy-induced damages to the epididymal epithelia mainly included cell swelling, local cavitation of mitochondria, tumor-like change in nucleoli, agglutination of marginal translocation of heterochromatin and cell apoptosis. The damage to the epithelial ultrastructure was slight in the treatment group as compared with the model rats. Chemotherapy significantly affected sperm concentration, sperm viability and sialic acid (SA), which were (15.59 +/- 4.01) x 10(6)/ml, (76.71 +/- 10.11)% and (19.38 +/- 9.34) g/mg prot in the model group in comparison with (10.63 +/- 3.82) x 10(6)/ml (P < 0.01), (60.03 +/- 7.54)% (P < 0.01) and (13.62 +/- 7.81) g/g prot (P < 0.05) in the control. Epimedium significantly increased sperm viability in the treatment group (60.03 +/- 7.54)% as compared with the model rats (69.90 +/- 12.58)% (P < 0.05).</p><p><b>CONCLUSION</b>Epimedium can lessen chemotherapy-induced damage to the epididymis and protect the reproductive function of rats.</p>

Alteration of signal transduction-associated gene expression in rat cardiac fibroblasts induced by blocking angiotensin II receptors / 生理学报

To investigate the molecular mechanism of angiotensin II (Ang II) receptor activation in adult rat cardiac fibroblasts, the expressions of cell signal transduction-associated genes were studied by using cDNA microarray. Cardiac fibroblasts of adult Sprague-Dawley rats (230~250 g) were isolated and cultured. The cells were divided into 4 groups: Ang II, Ang II + losartan, Ang II + PD123319, Ang II + losartan + PD123319. The expressions of Ang II receptors were studied by immunohistochemical staining. Total RNA was extracted and purified. After cDNA synthesis and biotin-16-dUTP labeling, the probes were denatured and hybridized with GEArray Q Series mouse G Protein-coupled Receptors Signaling Pathway Finder Gene Array (MM-025) containing 96 genes associated with 11 pathways. The arrays were scanned with a Uniscand1000 scanner and further analyzed with GEArray Analyzer software. RT-PCR was used to further confirm the results of gene microarray. The results of immunohistochemical staining showed that the expression of Ang II type 2 (AT2) receptor was evidently induced by Ang II stimulation when Ang II type 1 (AT1) receptor was blocked. The results of gene array indicated that blocking AT1 receptor changed 34 genes (more than 2 folds), 30 were down-regulated and 4 were up-regulated. The maximum change was not beyond 20 folds. The following 9 pathways were activated: cAMP/PKA, Ca2+, PKC, PLC, MAPK, PI-3 kinase, NO-cGMP, Rho, NF-kappaB pathways. Blockade of AT2 receptor caused 64 genes changing more than 2 folds (48 were down-regulated and 16 were up-regulated). Eleven pathways were basically activated. The change of the following 7 genes was over 30 folds: Cyp19a1 (37 folds), Il1r2 (42 folds), Cflar (53 folds), Bcl21 (31 folds), Pik3cg (278 folds), Cdkn1a (90 folds), Agt (162 folds). According to the activated extent, the signal transduction pathways in turn were PI-3 kinase, NF-kappaB and JAK-STAT pathways. Blocking both AT1 and AT2 receptors changed 46 genes more than 2 folds (36 were down-regulated and 10 were up-regulated). Eleven pathways were basically activated. The results of RT-PCR of IL-1beta and TNF-alpha confirmed the observations in gene microarray. Our results show that Ang II can induce a high expression of AT2 receptor in adult rat cardiac fibroblasts when AT1 receptor is blocked, and the signal mechanism of AT2 receptor is clearly different from that of AT1 receptor.