ABSTRACT
OBJECTIVE To investigate the effects of bilobalide (BB) on the myocardial tissue of rats with myocardial ischemia/reperfusion (Ml/R). METHODS An Ml/R model was prepared by ligating the anterior descending branch of the left coronary artery in rats for 30 min. BB 2, 4 and 8 mg-kg"1 was adminsterted for four weeks. The heart rate of rats was recorded and myocardial infarction area was detected. Detective kits were used to evaluate the concentrations of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). HE staining was performed to observe the myocardial injury, and TUNEL staining was performed to evaluate apoptosis. ELISA was performed to determine the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), IL-1p, tumor necrosis factor-a (TNF-a) and IL-10. Immunohistochemistry was performed to evaluate the expressions of Ki67 and interleukin-6 (IL-6). Western blotting was performed to evaluate the expressions of Bcl-2, Bax, cleaved-caspase 3, nuclear factor (erythroid-derived 2)-like 2 protein (Nrf2), heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQ01), NF-kB P65, phosphorylated inhibitor of NF-kB (P-IkBoc) and IkBcx kinase (p-IKK). RESULTS Compared with normal control group, the percentage of the myocardial infarction area and the concentration of CK-MB and LDH were increased in Ml/R model group, but heart rate was decreased (P<0.01) and myocardial tissue showed myocardial fiber rupture and inflammatory infiltration. Compared with Ml/R model group, the percentage of the myocardial infarction area and the concentration of CK-MB and LDH were decreased in Ml/R model+BB 2, 4 and 8 mg-kg"1 groups (P<0.05), but heart rate was increased (P<0.01) and myocardial tissue fibers tended to be regular while inflammatory cell infiltration was significantly reduced. Compared with normal control group, the percentage of apoptotic cells and Ki67 expression-positive cells and the expressions of Bax and cleaved-caspase 3 were increased in Ml/R model group (F<0.01), but the expression of Bcl-2 was decreased markedly (P<0.01). Compared with Ml/R model group, the percentages of apoptotic cells and Ki67 expression-positive cells and the expressions of Bax and cleaved-caspase 3 were decreased in Ml/R model+BB 2, 4 and 8 mg∗kg-1 groups (P<0.01), while the expression of Bcl-2 was increased (P<0.01). Ml/R could lower the activity of SOD and GSH-Px, but enhance MDA content. BB could weaken the effect of Ml/R on SOD, GSH-Px and MDA. Compared with normal control group, the concentrations of IL-1β, TNF-α and IL-10 in serum and the percentage of IL-6 expression-positive cells in myocardial tissue of Ml/R model group were increased (P<0.01). Compared with Ml/R model group, the concentrations of IL-1β and TNF-a and the percentage of IL-6 expression-positive cells were decreased in Ml/R model∗ BB 2, 4 and 8 mg-kg"1 group (P<0.01), but the concentration of IL-10 was increased(P<0.05). Compared with mormal control group, the protein levels of Nrf2, HO-1 and NQ01 significantly decreased (P<0.01), while the levels of NF-kB P65, p-IKK and p-kBa significantly increased (P<0.01). BB could effectively reverse protein changes (P<0.05, P<0.01). CONCLUSION BB can protect rats with Ml/R via anti-inflamma-tion and anti-oxidation.
ABSTRACT
<p><b>BACKGROUND</b>Gastric cancer (GC) is one of the most prevalent malignancies in the world today, with a high mortality rate. CDX2 is a Drosophila caudal-related homeobox transcription factor that plays an important role in GC. Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is an important tumor suppressor which is widely expressed in normal human tissues. The aim of the study was to determine the relationship and mechanism between CDX2 and PTEN in invasion and migration of GC cells.</p><p><b>METHODS</b>pcDNA3-CDX2 plasmids were transfected into MGC-803 cells to up-regulate CDX2 protein, and small interfering RNA-CDX2 was transfected to down-regulate CDX2. The influence of CDX2 or PTEN on cell migration and invasion was measured by invasion, migration and wound healing assays. Western blotting assay and immunofluorescence were used to detect the expression of CDX2, PTEN, phosphorylation of Akt, E-cadherin and N-cadherin. Statistical significance was determined by one-way analysis of variance.</p><p><b>RESULTS</b>The results showed that CDX2 reduced the migration and invasion of GC cells (P < 0.05), and inhibited the activity of Akt through down-regulating PTEN expression (P < 0.05). CDX2 also restrained epithelial-mesenchymal transition of GC cells.</p><p><b>CONCLUSIONS</b>CDX2 inhibited invasion and migration of GC cells by PTEN/Akt signaling pathway, and that may be used for potential therapeutic target.</p>