ABSTRACT
Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine . DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase 2 () deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level activating AMPK/UCP2, which were blunted by either AMPK or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity maintaining AMPK/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.
ABSTRACT
OBJECTIVE To investigate the effect of sodium ferulate (SF) on lipopolysaccharide (LPS)-induced preterm delivery and intra-uterine fetal death (IUFD). METHODS Pregnant Kunming mice were subcutaneously pretreated with SF (25 or 50 mg · kg-1) from gestational day (GD) 10 to GD 15 and with the single injection of LPS (150μg·kg-1, ip) on GD15.5. The incidence of preterm delivery and IUFD was observed. HE staining was used for uterine and placental histological evaluation. The levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) as well as the activities of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were detected in the maternal liver, placenta, and fetal liver using commercial kits. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in amniotic fluid were evaluated by enzyme linked immunosorbent assay. RESULTS For LPS group, the incidence of preterm was 47.8%, delivery time was (17.5 ± 1.3) d, and the pups′survival rate was only 42.6%. Compared with LPS-treated group, SF 50 mg · kg-1 group showed a lower incidence of preterm (14.3%, P<0.01), longer gestational days (18.4 ± 0.5, P<0.05), and a higher pups′survival rate (75.6%, P<0.01). SF 50 mg · kg-1 restored the LPS-induced GSH both in the maternal and fatal liver (a tendency without statistical significance), GST activity〔(163±82) kU·g-1 protein vs (95±90) kU·g-1 protein, P<0.01)〕in the placenta, TBARS content〔(2.5±0.4)μmol·g-1 protein vs (3.1±0.6)μmol·g-1 protein, P<0.01〕in the fetal liver, and TNF-αlevel〔(11±8) ng·L-1 vs (20±8) ng·L-1, P<0.01〕in the amniotic fluid. SF also attenuated LPS-induced placental congestion and neutrophil infiltra?tion in the uterus. CONCLUSION SF may protect against LPS-induced preterm delivery and IUFD, and anti-oxidation as well as anti-inflammation may contribute to these effects.
ABSTRACT
Objective The determination of skeletal maturity is an important measure for selecting sports talent. The characteristics of skeletal development of hand and wrist in Chinese children were investigated in order to compare with overseas experiences. Methods The subjects were 16035 children, aged 2～18 years. The skeletal maturity of hand and wrist of the subjects was estimated by TW3 method and was compared with that of European, European North American and Japanese children. Results In comparison with European and American children, Chinese and Japanese children showed a similar patterns of skeletal maturation. The TW3-RUS skeletal maturity of Chinese children was retarded by 0.3～0.6 year in boys at the age of 8～12 and was very close to European and American in girls at the age of 5～10. Older than 12 years of age in boys and 10 years of age in girls, the TW3-RUS skeletal maturity of Chinese children accelerated and became advanced by 1.1～1.6 years in boys, by 1.2 years in girls. As compared with European and American children, the TW3-carpal maturity delayed by 0.3～0.6 year in Chinese boys at the age of 3～10 and by 0.2～0.4 year in Chinese girls at the age of 2～5. The TW3-carpal maturation accelerated after age of 10 in boys and age of 5 in girls. The age of complete maturity in all carpals was advanced by 1.4 year in boys and girls. Conclusion As compared with European and American children in 1970s-1990s, the delay of skeletal development of hand and wrist in Chinese children was not obvious in childhood, and the extent of advanced skeletal maturity and the age of advanced complete maturity of Chinese children are more evidently.