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Triptolide into angiotensin II induced newborn rat heart fibroblast proliferation and collagen synthesis of its mechanism

Author: ZhangZuo
Tutor: ZhangZhenGang
School: Yangzhou University
Course: Traditional Chinese Medicine
Keywords: Myocardial fibrosis Cardiac fibroblasts Angiotensin II Collagen synthesis Proliferation Hydroxyproline Transforming growth factor β1 Triptolide Promoting mitogen protein - activated kinase
CLC: R285.5
Type: Master's thesis
Year: 2009
Downloads: 82
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Abstract

Background: The myocardial fibrosis (myocardial fibrosis, MF) in various fibrogenic factors disproportionate increase in myocardial collagen fibers. Its main causes, including ischemic heart disease (cardiomyopathy), hypertensive heart disease, inflammatory cardiomyopathy, metabolic cardiomyopathy, hypertrophic cardiomyopathy. Heart by myocardial cells and stromal cells, stromal cells accounted for 2/3 of the total number of heart cells, the cardiac fibroblasts vast majority (gt; 90%). The proliferative ability of cardiac fibroblasts, constitute myocardial interstitial network structural proteins I and collagen type III its secretion. In the process of myocardial fibrosis, heart into fibroblast proliferation and collagen synthesis and secretion increased myocardial interstitial structure remodeling, these changes will result in abnormal myocardial metabolism and function, so that the stiffness increased, systolic and diastolic dysfunction, and ultimately lead to heart failure. Triptolide (Triptolide, TP) as a nonspecific immunomodulatory drugs widely used in clinical treatment of rheumatism and other autoimmune diseases for many years, domestic and foreign scholars study found, TP can be suppressed eye fibroblasts and skin keloid fibroblasts proliferation, but its impact on myocardial fibrosis, yet reported. Animal studies before this research group found that TP can inhibit the spontaneously hypertensive rat myocardial fibrosis, but the exact mechanism has not been elucidated. Therefore, the purpose of this experimental study is to observe the TP is able to inhibit the proliferation and collagen synthesis of cardiac fibroblasts, which play the role of the reversal of cardiac fibrosis, based on further explore the mechanism of the TP reversal of myocardial fibrosis. Objective: To observe the TP is able to inhibit the proliferation and collagen synthesis of cardiac fibroblasts, which play the role of the reversal of myocardial fibrosis, and to explore the possible mechanism of the TP reversed myocardial fibrosis. Method: digestion method to obtain the culture neonatal SD rat cardiac fibroblasts. Experimental groups: control group: containing DMEM culture medium; groups of AngII: culture medium was added to a final concentration of 10-7mol / L AngII; TP (100μg / L) group: the culture solution was added to a final concentration of 100μg / L TP and 10-7mol / L AngII; TP (10μg / L) group: culture medium while adding 10μg / L TP and 10-7mol, / L AngII; TP (1μg / L) group: while adding culture medium 1μg / L TP and 10-7mol, / L AngII. MTT colorimetric assay of cell proliferation; the hydroxyproline determination collagen synthesis; ELISA assay secretion of TGF-β1; WesternBlot detection MAPK extracellular signal-regulated kinase 1/2 (ERK1 / 2) content. Observed AngII on myocardial into fibroblast proliferation and collagen synthesis of the intervention effect of different concentrations of TP. Results: 1 and compared to the control group, join AngII significantly promoted CFb the proliferation (P lt; 0.05 or P lt; 0.01) high concentrations of TP (100μg / L) in 24 hours of drug action is shown to inhibit CFb proliferation (P lt; 0.01), in the 48 hours up to the peak (P lt; 0.001), 72 hours later, began to weaken. Step TP play the efficacy of the best time in about 2 to 3 days. 2, with the the AngII role of time increase, increase in collagen synthesis of content and control group comparison have significant significant difference (P lt; 0.05 or P lt; 0.01), the TP role 24h, 48h, 72h after each group of collagen content and AngII group comparison are There are significant differences, the high concentration group TP (100μg / L) reached a peak at 48 hours (P lt; 0.001). AngII for 24 hours, TGF-β1 expression was significantly increased (P lt; 0.01), after adding different concentrations of TP for 24 hours, TGF-β1 expression levels were significantly lower (P lt; 0.05 or P lt; 0.01). 4, AngII role after 30min, ERK1 / 2 phosphorylation level of the negative control group was significantly enhanced (P lt; 0.05); join 100μg / L TP 30min after p-ERK1 / 2 expression and AngII group compared decreased (P lt; 0.05); 1μg / L, 10μg / L TP failed to significantly inhibit AngII caused ERK1 / 2 phosphorylation; positive control drug U0126 significantly inhibited the phosphorylation of ERK1 / 2 of (P lt; 0.01 ). Conclusion: AngII has a role in promoting neonatal SD rat cardiac fibroblast proliferation and collagen synthesis, and its possible mechanism is via the MAPK signaling transduction pathway, to promote the expression of phosphorylated ERK1 / 2 play the role of promoting cardiac fibroblasts proliferation ; by increasing the expression of TGF-β1 and play a role in promoting collagen synthesis. Triptolide significantly inhibited AngII-induced myocardial into fibroblast proliferation and collagen synthesis, and a dose-dependent manner, the mechanism may play a role by inhibiting the phosphorylation of ERK1 / 2 and reduce the expression of TGF-β1.

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