ABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of carvedilol on the expression of Bcl-2, Bax and Fas in autoimmune myocarditis (AM).</p><p><b>METHODS</b>A total of 60 inbred male BALB/C mice 4 - 5 weeks of age were divided at random into 3 groups as follows: AM group (n = 20), carvedilol group (n = 20) and control group (n = 20). The mice were sacrificed after gathering blood specimens by taking out the eyeballs and hearts tissue. The histological and ultrastructural changes were observed under light microscope and electron microscope. The concentrations of cardiac troponin I (cTn I) were detected by chemiluminescence immunoassay (CLIA). Immunohistochemistry (IHC) was performed to analyze the contents of Bcl-2, Bax and Fas, TUNEL to detect the apoptotic index in myocardial cells.</p><p><b>RESULTS</b>There were large number of lymphocyte and monocyte infiltrates under light microscope and karyopyknosis and chromatin gathered along the nuclear membrane under electron microscope in AM group. There were no inflammations and chromatin gathering in group C. Compared with control group, the Bcl-2, Bax and Fas protein expression significantly elevated in AM group (23.48 ± 2.24 vs. 6.64 ± 1.60, 26.15 ± 2.02 vs. 5.09 ± 0.85, 21.22 ± 3.62 vs. 5.86 ± 1.37, P < 0.01). The histopathologic scores (2.60 ± 0.31 vs. 2.02 ± 0.26, P < 0.05) and karyopyknosis of carvedilol group decreased as compared with AM group. The Bcl-2, Bax and Fas protein expression (17.13 ± 1.94 vs. 23.48 ± 2.24, 17.66 ± 2.62 vs. 26.15 ± 2.02, 16.79 ± 2.83 vs. 21.22 ± 3.62, P < 0.05), AI [(16.61 ± 4.67)% vs. (24.51 ± 4.70)%, P < 0.05] and contents of cTnI [(1.878 ± 0.48) ng/ml vs. (1.102 ± 0.23) ng/ml, P < 0.05] also decreased in carvedilol group compared with AM group.</p><p><b>CONCLUSION</b>Carvedilol could protect against AM by alleviating cardiomyocyte apoptosis.</p>
Subject(s)
Animals , Male , Mice , Adrenergic beta-Antagonists , Pharmacology , Apoptosis , Autoimmune Diseases , Metabolism , Pathology , Carbazoles , Pharmacology , Mice, Inbred BALB C , Myocarditis , Metabolism , Pathology , Myocytes, Cardiac , Metabolism , Propanolamines , Pharmacology , Proto-Oncogene Proteins , Metabolism , Proto-Oncogene Proteins c-bcl-2 , bcl-2-Associated X Protein , Metabolism , fas Receptor , MetabolismABSTRACT
<p><b>OBJECTIVE</b>Previous studies have shown that hydrogen sulfide (H2S) plays key roles in a number of biological processes, including vasorelaxation, inflammation, apoptosis, ischemia/reperfusion and oxidative stress, which are involved in the pathogenesis of myocarditis. This study aimed to examine the expression of cystathionine-γ-lyase(CSE)/H2S pathway in mice with viral myocarditis.</p><p><b>METHODS</b>Six-week-old inbred male mice were randomly assigned to control (n=25) and myocarditis group (n=30). The myocarditis and the control groups were inoculated intraperitoneally with 0.1 mL 10-5.69TCID50/mL CVB3 or vehicle (PBS) alone respectively. Ten mice were sacrificed 4 and 10 days after injection. Blood and heart specimens were harvested for measuring the content of serum H2S and the H2S production rates in cardiac tissues. Heart sections were stained with hematoxylin and eosin. Immunohistochemisty was used to detect the CSE protein expression in the heart.</p><p><b>RESULTS</b>In the myocarditis group, the serum H2S content and H2S production rates in cardiac tissues were significantly higher than those in the control group 4 and 10 days after injection (P<0.05). The expression of CSE protein in the heart in the myocarditis group was also significantly higher than that in the control group (P<0.05).</p><p><b>CONCLUSIONS</b>CSE and its downstream production H2S increase in mice with acute viral myocarditis. The increased expression of CSE/H2S pathway might be involved in the pathogenesis of viral myocarditis.</p>