ABSTRACT
ABSTRACT Purpose To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2). Methods Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2+ macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE-/- mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1β and TNF-α. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining. Results We found that Ang II activated the expression of CXCR2 in monocytes during the formation of AAA. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of 1β and TNF-α, which were then partly abolished by SB225002. Conclusions CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.
Subject(s)
Animals , Mice , Aortic Aneurysm, Abdominal/prevention & control , Aortic Aneurysm, Abdominal/drug therapy , Apolipoproteins E/genetics , Angiotensin II , Receptors, Interleukin-8B , Disease Models, Animal , Macrophages , Mice, Inbred C57BLABSTRACT
OBJECTIVE@#To investigate the effect of high mobility group protein box 1 (HMGB1) on apoptosis of astrocytes after oxygen glucose deprivation/reoxygenation (OGD/R), and to investigate the possible mechanism by evaluating the expression of apoptosis related protein Bcl-2 and Bax.@*METHODS@#The cerebral cortex astrocytes of neonatal rats were divided into normal group, model group, interference group and control group. Lentivirus vector of rat HMGB1 short hairpin RNA (shRNA) was used to suppress the HMGB1 protein expression in the astrocytes. Then the detection was made after astrocytes were deprived of oxygen and glucose 6 h, reoxygenation for 24 h. The effect of RNA interference was evaluated by Western blotting. The cell survival rate was measured by MTT assay. The apoptosis of astrocytes was determined by TUNEL assay. The expressions of Bcl-2 and Bax were detected by Western blotting.@*RESULTS@#Compared with the normal group, the protein expression of HMGB1 was significantly increased in model group after OGD/R (P<0.001), the astrocytes survival rate was decreased (P<0.001), the number of apoptotic cells labeled with TUNEL was increased (P<0.001), and the ratio of Bcl-2/Bax was decreased (P<0.001). Compared with the model group, RNA interference effectively inhibited the expression of HMGB1 in interference group (P<0.001), the astrocytes survival rate was increased (P<0.001), the number of apoptotic cells labeled with TUNEL was reduced (P<0.01), and the ratio of Bcl-2/Bax was increased (P<0.001).@*CONCLUSION@#The apoptosis of astrocytes can be induced by HMGB1 after OGD/R, and the mechanism may be related to regulating the expression of apoptosis related proteins Bcl-2 and Bax.
Subject(s)
Animals , Rats , Apoptosis , Astrocytes , Cell Hypoxia , Cells, Cultured , Glucose/metabolism , HMGB1 Protein/physiology , Oxygen , Proto-Oncogene Proteins c-bcl-2 , Rats, Sprague-Dawley , bcl-2-Associated X Protein/metabolismABSTRACT
Early diagnosis of esophageal cancer is essential for improving both the effectiveness of esophageal cancer treatment and the prognosis of patients.As a new technology for esophageal cancer early diagnosis,narrow-band imaging (NBI) enables surgeon to clearly observe the mucosa and submucosal blood vessels changes in early esophageal cancer.It has initially shown excellent application value in the early diagnosis.In particular it has obvious advantages to the ordinary white light endoscopy which is currently used in esophageal cancer early diagnosis.If combined with Lugol iodine staining,magnifying endoscopy and other diagnostic methods in clinical,NBI will have a better value in early diagnosis of esophageal.