ABSTRACT
Viral myocarditis (VMC) is a type of cardiovascular disease caused by viral infection of myocardial cells characterized by myocardial interstitital inflammatory cell infiltration, myocardial fiber necrosis or figrinolysis. Ivabradine (IVA) is a commonly known drug used to control heart rate, resist inflammation and oxidative stress, particularly in VMC. Here, we have tried to evaluate the protective effects of IVA on mice with VMC and understand the possible mechanism behind this process. In order to complete the study, eighty male mice aged 6 weeks old were randomly divided into normal control, VMC model, low-dose IVA (L-IVA) and high-dose IVA (H-IVA) groups. Half an hour after modeling, IVA aqueous solution was administered intragastrically into L-IVA and H-IVA groups at 5 mg·kg-1·d-1 and 20 mg·kg-1·d-1, respectively for 14 consecutive days. Another 120 mice of the same batch were grouped and treated as described above. At 7 and 14 d, 6 mice in each group were sacrificed to obtain blood and heart samples. Body weight/heart weight (BW/HW) was calculated, hematoxylin-eosin staining was performed to observe the pathological changes of myocardium, and the level of cardiac troponin I (cTnI) was measured by ELISA. Related kits were employed to measure superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and catalase (CAT) activites in myocardial homogenate, and the levels of interleukin-6 (IL-6), IL-18, IL-1? and tumor necrosis factor-? (TNF-?) were determined by double-antibody sandwich ELISA. TUNEL assay was performed to detect the apoptosis of myocardial cells. The protein expressions of Bcl-2, Bax and Caspase-3 in myocardial cells were measured by Western blotting. Compared to the VMC model group, the heart/body weight ratio, myocardial pathological score, cTnI level, MDA activity, and levels of IL-6, IL-18, IL-1? and TNF-? were found decreased, while survival rate and activity of SOD, GSH-Px and CAT increased in L-IVA and H-IVA groups (P <0.05). The apoptosis rate of myocardial cells declined in L-IVA and H-IVA groups (P <0.05), especially in H-IVA group. IVA downregulated the protein expressions of Bax and Caspase-3 and upregulated that of Bcl-2 (P <0.05). Thus, it has been found that IVA elevates the survival rate of VMC mice and relieves myocardial damage possibly by enhancing antioxidant capacity and modulating apoptosis-related proteins to suppress apoptosis.
ABSTRACT
The biomarkers associated with coronary artery lesions (CAL) secondary to Kawasaki disease (KD) in Chinese children were investigated by using Meta-analysis.We searched documents published from January 1997 to December 2009 from medical electronic databases.According to inclusion and exclusion criteria,eligible full-text papers were identified.We conducted a comprehensive quantitative analysis by using Statal 0.0 statistical software package to assess the heterogeneity among the documents,calculated the summary effect and analyze publication bias and sensitivity.A total of 92 documents and 16 biomarkers were identified.All documents were case-control studies,and included 2398 patients in CAL group and 5932 patients in non-CAL (NCAL) group.The Meta-analysis showed that the levels of platelet count,platelet hematocrit (PCT),neutrophils count,platelet distribution width (PDW),mean platelet volume (MPV),erythrocyte sedimentation rate (ESR),cardiac troponin Ⅰ (cTnI),and endothelin-1 (ET-1) in CAL group were significantly higher than those in NCAL group,and serum albumin (Alb) and hemoglobin (Hb) levels were significantly lower in CAL group (all P＜0.05).White blood cell (WBC) count,serum sodium,matrix metalloproteinase 9 (MMP-9),total cholesterol (TC),hematocrit (HCT) and CD3+T lymphocytes percentage had no statistically significant difference between the two groups.In conclusion,our results indicated that the 10 biomarkers including platelet count,neutrophils count,PCT,PDW,MPV,ESR,cTnI,ET-1,Alb and Hb were associated with CAL,and may be involved in the pathogenesis of CAL.The biomarkers of WBC count,serum sodium,MMP-9,TC,HCT,and CD3+T lymphocytes percentage bore no relationship with the development of CAL among Chinese children with KD.