ABSTRACT
In this study, the role of the RhoA/Rho-kinase (RhoA/ROCK)-signaling pathway in cardiovascular dysfunction associated with hyperthyroidism was examined with the use of fasudil, a Rho-kinase inhibitor. Male Spraque-Dawley rats were treated with l-thyroxine (T(4)) alone, T(4) + low-dose fasudil (2 mg/kg/day) or T(4) + high-dose fasudil (10 mg/kg/day) and compared with control animals. Rats in the T(4) group showed an increase in the ratio of heart weight to body weight, which was ameliorated by fasudil at both low and high doses. Morphometric and hemodynamic parameters were also evaluated and confirmed that fasudil attenuated the cardiac hypertrophy induced by T(4). The extent of phosphorylation of the myosin phosphatase targeting subunit was quantified by Western blotting to evaluate the activity of Rho-kinase in the heart tissue. Both Western blotting and reverse transcriptase-polymerase chain reaction analyses revealed enhancement of Rho-kinase and activator protein 1 activity and reduction of c-FLIP(L) expression in the T(4) group, and this response was inhibited by fasudil in a dose-dependent manner. Furthermore, fasudil inhibited apoptosis induced by T(4) as evidenced by the detection of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and the expressions of bax and bcl-2. These results suggested that the RhoA/ROCK pathway is involved in the cardiac hypertrophy induced by experimental hyperthyroidism. The antagonism of this pathway may thus be useful as an alternative target in the treatment of hyperthyroid heart disease.
Subject(s)
Cardiomegaly/physiopathology , Hyperthyroidism/physiopathology , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/metabolism , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/administration & dosage , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Animals , Apoptosis/drug effects , Cardiomegaly/drug therapy , Dose-Response Relationship, Drug , Heart/drug effects , Hyperthyroidism/chemically induced , In Situ Nick-End Labeling , Male , Organ Size , RNA/isolation & purification , Rats , Rats, Sprague-Dawley , Signal Transduction , Thyroxine/administration & dosage , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , rho-Associated Kinases/genetics , rhoA GTP-Binding Protein/geneticsABSTRACT
Objective: To study the influence of Centipede Acidic Protein(CAP) on the proliferation and collagen synthesis of cultured neonatal rat cardiac fibroblasts(CFb) induced by angiotensinⅡ(AngⅡ),and to explore the mechanisms of CAP on cardiac fibrosis.Methods: Neonatal rat cardiac fibroblasts were treated with AngⅡ to produce fibrosis model.The effects of CAP on proliferation of CFb were observed by MTT colorimetric assay,synthesis of collagen was observed by the hydroxyproline concentration.The NO contents were measured by Nitric acid reductase method.The c-myc expression was examined by semi-quantitative RT-PCR analysis.Results: Compared with that of control group,the proliferation,collagen synthesis and the levels of c-myc mRNA expression of CFb in the model group increased,while the NO contents decreased obviously(P
ABSTRACT
OBJECTIVE:To study the effects of Chongcaodihuang(CCDH)syrupus on immune function and antistress ability.METHODS:The experiments were carried out to investigate the effects of CCDH on weight of immune organs,the phagocytization of the monocytes by using the method of carbon particles expurgation,the content of antibody of hemolysin in serum,and time of swimming and hypoxia tolerance in mice.RESULTS:CCDH could enhance weight of immune organs,the phagocytization of the monocytes and increase the content of antibody of hemolysin in serum.It can also delay the time of swimming and strengthen hypoxia tolerance in mice.CONCLUSION:CCDH significantly improve immune function and antistress ability of mice.
