Protective effect of ivabradine on mice with viral myocarditis and its mechanism

549-556Viral 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. 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 wt./heart wt. (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) activities in myocardial homogenate, and the levels of interleukin-6 (IL-6), IL-18, IL-1β and tumor necrosis factor-α (TNF-α) 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-1β and TNF-α 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

Protective effect of ivabradine on mice with viral myocarditis and its mechanism

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-1β and tumor necrosis factor-α (TNF-α) 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-1β and TNF-α were found decreased, while survival rate and activity of SOD, GSH-Px and CAT increased in L-IVA and H-IVA groups (P &lt;0.05). The apoptosis rate of myocardial cells declined in L-IVA and H-IVA groups (P &lt;0.05), especially in H-IVA group. IVA downregulated the protein expressions of Bax and Caspase-3 and upregulated that of Bcl-2 (P &lt;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

Dynamics of Structural Dry Matter, Water Soluble Carbohydrates and Leaf Senescence Mediate the Response of Winter Wheat Yield to Soil Cover and Water Availability

Plastic film mulching often increases the yield of winter wheat in the Loess Plateau of China, but the physiological mechanisms are unclear, especially in response to the interaction between mulch and water supply. In this study, we investigated the interactive effects of initial soil water (dry, moderate, and wet), soil cover (plastic mulch, bare soil), and seasonal conditions on the dynamics of dry matter partitioning, water-soluble carbohydrates (WSC), and flag leaf senescence, and their relations with yield and its components. Plastic mulch increased dry matter accumulation at anthesis and maturity relative to bare soil, with no interaction with season or initial soil water. Allocation of dry matter to leaf, stem, and spike did not change with soil cover. Compared with bare soil, mulch increased WSC accumulation by 14% at anthesis and its translocation by 16%. Soil cover did not influence the senescence of flag leaf after anthesis as indicated by similar dynamics of the C:N ratio. Grain yield was higher under plastic mulch than bare soil in two out of three seasons, and was associated with a higher translocation amount of WSC and post-anthesis dry matter that linked grain weight, grain number, and harvest index

Dynamics of Structural Dry Matter, Water Soluble Carbohydrates and Leaf Senescence Mediate the Response of Winter Wheat Yield to Soil Cover and Water Availability

Plastic film mulching often increases the yield of winter wheat in the Loess Plateau of China, but the physiological mechanisms are unclear, especially in response to the interaction between mulch and water supply. In this study, we investigated the interactive effects of initial soil water (dry, moderate, and wet), soil cover (plastic mulch, bare soil), and seasonal conditions on the dynamics of dry matter partitioning, water-soluble carbohydrates (WSC), and flag leaf senescence, and their relations with yield and its components. Plastic mulch increased dry matter accumulation at anthesis and maturity relative to bare soil, with no interaction with season or initial soil water. Allocation of dry matter to leaf, stem, and spike did not change with soil cover. Compared with bare soil, mulch increased WSC accumulation by 14% at anthesis and its translocation by 16%. Soil cover did not influence the senescence of flag leaf after anthesis as indicated by similar dynamics of the C:N ratio. Grain yield was higher under plastic mulch than bare soil in two out of three seasons, and was associated with a higher translocation amount of WSC and post-anthesis dry matter that linked grain weight, grain number, and harvest index