In order to investigate the changes in the expression of extracellular signal-regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF>-6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2-mRNA was increased in the patients with CAF (74±19 U vs sinus rhythm: 32±24 U,P<0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150% in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three-fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.
To investigate the effect of atorvastatin on lipid metabolism in type 2 elder diabetes patients with hyperlipidemia, 26 patients with type 2 elder diabetes complicated with hyperlipidemia were treated with atorvastatin (10 mg/d) for 8 weeks. The serum triglyceride (TG), high density protein cholesterol (HDL-C) and low density protein cholesterol (LDL-C) were measured before and after the treatment. Meanwhile, the non-denaturing polyacrylamide gradient gel electrophoresis was used for detection of small-sized LDL (SLDL). Our results showed that TG dropped from 4.88±0.72 mmol/L to 2.65±0.32 mmol/L; HDL-C was increased from 0.85±0.31 mmol/L to 1.28±0.29 mmol/L; LDL-C was declined from 3.71±2.98 mmol/L to 2.10±1.22 mmol/L, sLDL-A was increased from (42.49±8.1)% to (53.27±7.5)%; LDL-B was decreased from (57.91±8.1)% to (46.73±7.5%) (P<0.05). The level of blood glucose was not changed at the end of 8th week. It is concluded that atorvastatin has satisfactory lipid-regulating effects on type 2 elder diabetes patients with hyperlipidemia.
The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group, dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB, intercellular adhering molecule 1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-κB activation and expression.
To study the mechanisms involved in the inhibition of chronic myeloid leukemic cells (K562) proliferation induced by arsenic trioxide (As2O3) and to explore the potential role of Survivin, an inhibitor of apoptosis protein, in the regulation of As2O3 induced cell apoptosis, K562 cells were cultured with As2O3 of different concentrations. Cells were collected for proliferation analysis by MTT assay. Cell cycle distribution and cell apoptosis were analyzed by flow cytometry. Expression of Survivin protein and mRNA were detected by flow cytometry and RT-PCR, respectively. Our results showed that As2O3 (2–10 μmol/L) inhibited K562 cells growth effectively, but it did not induce cells apoptosis significantly. The percentage of K562 cells at G2/M phase increased in proportion to As2O3 concentrations, and the expression of Survivin mRNA and content of Survivin protein was up-regulated accordingly. It is concluded that As2O3 inhibited K562 cells growth by inducing cell cycle arrest mainly at G2/M phase. Over-expression of Survivin gene and protein might be one of the possible mechanisms contributing to K562 cells resistance to As2O3-induced apoptosis.
To investigate the role of mitochondria in neuronal apoptosis, ischemia-reperfusion mediated neuronal cell injury model was established by, depriving of glucose, serum and oxygen in media. DNA fragmentation, cell viability, cytochrome C releasing, caspase3 activity and mitochondrial transmembrane potential were observed after N2a cells suffered the insults. The results showed that N2a cells in ischemic territory exhibited survival damage, classical cell apoptosis change, DNA ladder and activation of caspase3. Apoptosis-related alterations in mitochondrial functions, including release of cytochrome C and depression of mitochondrial transmembrane potential (ΔΓm) were testified in N2a cells after mimic ischemia-reperfusion. Moreover, activation of caspase3 occurred following the release of cytochrome C. However, the inhibitor of caspase3, Ac-DEVD-CHO, couldn't completely rescue N2a cells from apoptosis. Administration, of cyclosporine A, an inhibitor of mitochondria permeability transition pore only partly inhibited caspase3 activity and reduced DNA damage. Interestingly, treatment of Z-IETD-FMK, an inhibitor of caspase8 could completely reverse DNA fragmentation, but can't completely inhibit caspase3 activity. It was concluded that there were caspase3 dependent and independent cellular apoptosis pathways in N2a cells suffering ischemia reperfusion insults. Mitochondria dysfunction may early trigger apoptosis and amplify apoptosis signal.