| Chronic heart failure (HF), the terminal manifestation of various cardiovascular diseases, has been focused in the modern clinical medicine for its high rate mortality and great treatment difficulty. In pre-clinical and clinical studies of cardiovascular diseases, HF prevention and treatment has ever been the main task. Although, modern medicine has achieved progresses in HF treatment, its clinical application is still limited due to the evident toxic side effects. As deeper research goes into HF, great attentions have been attached to traditional Chinese medicine (TCM) in that it has less toxic side effects and more persistent curative effects. Therefore, it is of great significance to explore into HF prevention and treatment employed by TCM.The heart-qi deficiency, TCM considers, is the most common syndrome of HF, and affects its whole course. However, blood stasis syndrome accompanying heart-qi deficiency is the frequently observed excess manifestation. Qi deficiency and blood stasis are the underlying pathology and pathogenesis. As HF worsens, syndromes like dual deficiency of qi and yang, prostration of yang-qi, and dampness stagnation will develop. Qi deficiency and blood stasis affect each other, interacting as both cause and effect, thus a vicious circle of pathological deficiency and excess will develop. The key point to block such circle is to invigorate qi and enhance blood circulation. Moreover, cardiovascular pharmacological studies on qi- invigorating and blood circulation enhancing Chinese medicines reveal that, such medicines can ameliorate ventricular reconstruction in HF patients.It is critical of myocardial fibrosis for the cardiac function change from compensatory to non-compensatory phase, and its reduction can restore the balance between myocardium tissue and stroma, normalize myocardium stiffness, and improve cardiac function. The normalization of target organ depends on that of interstitial structures. Therefore, it is very important to block the link of fibrosis and to reverse fibrotic lesion. A new method for the treatment of heart failure is provided by preventing and reversing ventricular remodeling.In recent several years, clinical and experimental studies have shown that one of main reasons of ventricular reconstruction is the stimulation of AngⅡ on type I collagen proliferation, and AngⅡ plays a key role in myocardium fibrosis. Thus, based on these, we selected the bioactive components contained in qi-invigorating drugAstragalus, blood circulation-enhancing drug Szechuan Lovage Rhizome and Radix Salviae Miltiorrhizae, which are astragalosides, ligustrazine and Tanshinones II a respectively, to study their effects on the proliferation of cardiac fibroblast induced by AngⅡ. type I collagen contents, mRNA expression and the regulation role of type I collagen gene promoter. We expect to investigate the pathologic mechanism of myocardium fibrosis in the level of cell and gene transcription, and provide experimental basis for TCM reversing ventricular remodeling, preventing and treating HF.The experimental results confirms that AngⅡ in vitro can cause the proliferation of cardiac fibroblast directly, accelerate the secretion of type I collagen, increase the mRNA expression of type I collagen, and enhance the priming activity of pCOLH2.5 fragment markedly. They also indicate that the regulation of AngⅡ on type I collagen occurs at the transcription level, and its response element may locate in the upstream of 5' flanking regions-2483 ~+42bp. It contributes to the role of AngⅡ on promoter. AngⅡ results in fibrosis through the same pathologic mechanism, and it is a strong cytokine inducing fibrosis. AngⅡ can not only adjust the type I collagen expression at the transcription level, but also accelerate the secretion of TGF-β through the binding to AT1 receptor, stimulate the secretion of stromatin from cardiac fibroblast, increase the synthesis of collagen, at the same time, decrease the activity of collagenase, and inhibit the degradation of collagen to accelerate fibrosis.Losartan, a...
|
PDF Full Text Request