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The Effects Of Triptolide On The Improvement Of Left Ventricular Remodeling In The Rats With Pressure Overload

Posted on:2009-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y NiFull Text:PDF
GTID:2144360242993552Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Backgrounds:Congestive heart failure (CHF), a final common pathway in many cardiovascular diseases, has become a public health problem for human beings. The better understanding in the pathogenesis of CHF results in continual progress in its treatment. The heart ventricular remodeling is the basic mechanism of heart failure. In recent years accumulating data show that proinflammatory cytokines, as a new neurohumoral factor may play an important role in the development of ventricular remodeling besides the activation of the neuroendocrine system, which can take part in the initiation and development of heart failure and ventricular remodeling through many ways, such as inducing myocardial hypertrophy, apoptosis and necrosis and regulating myocardial stroma remodeling. The non-specific immunomodulation on the activation of inflammatory mediators in heart failure has displayed a bright future in CHF therapy. Triptolide as a non-specific immunomodulator, not only has a wide regulation on the inflammatory mediators, but also can inhibit NF-κB activation.Objectives:It is aimed to explore the effects of the triptolide on the left ventricular remodeling and cardiac function in the pressure overload rats, as well as the adjustment of the peripheral blood expression of inflammatory mediators and its mechanism.Methods:The rats with pressure overload were induced by the coarctation of abdominal aorta. The model rats were divided randomly into 5 groups: sham-operation group (group A),model control group (group B),triptolide group with low dose (6μg/kg.d, group C),triptolide group with moderate dose (9μg/kg.d, group D),triptolide group with high dose (12μg/kg.d, group E). They were respectively intraperitoneal injected with saline (1.0 ml/ kg.d, group A), saline (1.0 ml/ kg.d, group B) and triptolide (group C, group D, group E) for 8 weeks. Cardiac structure and function were assessed by echocardiography after treatment. LVMI was determined by electronic balance after treatment. The change of structure and shape in myocytes was observed with hematoxylin and eosin dying. The collagen volume fraction (CVF %) and perivascular collagen area (PVCA %) were determined with Masson specific dying. Type I collage and type III collagen were investigated by immunohistochemistric assays and calculated ratio of collage I/III. The serum levels of TNF-α,IL-1,IL-6,IL-10 and MCP-1 were determined by ELISA. The nuclear DNA binding of NF-κB and the transactivation of NF-κB were determined by ELISA.Results:1. The echocardiography showed that compared with group A, LVPWT and IVST in group B were increased (P<0.05), after the treatment with triptolide, it showed no significantly change compared with group B (P>0.05), while LVEF in group B was lower than that in group A (P<0.05), after the treatment with triptolide, it was increased, but it showed no significant difference compared with group B (P>0.05).2. LVMI in group B was much higher than that in group A (P<0.05), after the treatment with triptolide, LVMI in group C,D,E were decreased, but not reached significant difference compared with group B (P>0.05).3. Compared with group A, Hematoxylin-eosin staining showed that cardiac muscle cell hypertrophy and cardiac muscle fibers arrangement were obvious, the vessel wall became much more thicker, and the infiltration of inflammatory cells in myocardium were increased significantly in group B. After the treatment with triptolide, only the infiltration of inflammatory cells in myocardium showed significantly change compared with group B (P<0.01).4. Masson special staining showed that the collagen volume fraction and perivascular collagen area in group B were significantly increased compared with group A (P<0.01). After the treatment with triptolide, the collagen volume fraction was significantly decreased (P<0.01), while the perivascular collagen was decreased, but not reached significant difference compared with group B (P>0.05). There were no significant differences among the three groups (group C,D,E) (P>0.05).5. Immunohistochemistry showed that compared with group A, the amount of type I collage and type III collagen proteins in myocardium stroma and the ratio of I/III in group B were significantly increased (P<0.01), after the treatment with triptolide, compared with group B, the amount of type I collage was significantly decreased (P<0.01) and the amount of type III collagen was significantly increased (P<0.01), the ratio of I/ III was significantly decreased (P<0.01), there were no differences among the three groups (group C,D,E) (P>0.05).6. Compared with group B, the content of IL-6 in group A was increased (P<0.05), after the treatment with triptolide, the content of IL-6 was decreased, it showed no difference in group C (P>0.05), while it showed significant difference in group D and group E (P<0.01); Compared with group B, the content of IL-1 in group A was increased (P<0.05), after the treatment with triptolide, the content of IL-6 was decreased, it showed no difference in group C (P>0.05), while it showed significant difference in group D and group E (P<0.05); Compared with group B, the content of TNF-αin group A was increased (P>0.05), after the treatment with triptolide, the content of TNF-αwas decreased, and it showed significant difference only in group E (P<0.05); The content of IL-10 in group A was decreased in comparison with that in group B (P<0.01), after the treatment with triptolide, the content of IL-10 in group C was decreased, but it showed no significant difference (P>0.05), While the content of IL-10 in group D was decreased (P<0.05) and it was decreased in group E (P<0.01); Compared with group A, the content of MCP-1 in group B was increased, but it showed no significant difference (P>0.05), after the treatment with triptolide, it was significantly decreased in three groups (group C,D,E) (P<0.01), and there were no differences among the three groups (group C,D,E) (P>0.05).7. Compared with group A, the transactivation of NF-κB was significantly increased in group B (P<0.01), after the treatment with triptolide, it was significantly decreased in group C,D,E (P<0.01), there were no differences among the three groups (group C,D,E); Compared with group A, the nuclear DNA binding of NF-κB was significantly increased in group B (P<0.05), after the treatment with triptolide, it showed no significant difference in group C,D,E (P>0.05).Conclusions:Triptolide has no significant effect on hypertrophy in the pressure overload rats, triptolide can modulate serum levels of cytokines, attenuate cardiac fibrosis; Triptolide may play the role of non-specific immunomodulation effect through the inhibition on the activation of the NF-κB pathway.
Keywords/Search Tags:heart failure, ventricular remodeling, immunomodulation, cytokine, triptolide
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