Dissertation > Medicine, health > Internal Medicine > Respiratory system and chest diseases > Trachea and bronchial disease > Bronchial disease > Bronchial asthma

Effects of Valsartan, a Type 1 Angiotensin Ⅱ Receptor Antagonist, on Airway Smooth Muscle Cells Proliferation

Author ShengNa
Tutor WangTong
School Nanjing Medical University
Course Internal Medicine
Keywords Valsartan Airway smooth muscle cells Cell proliferation TGF-β1 Angiotensin II receptor
CLC R562.25
Type Master's thesis
Year 2009
Downloads 28
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Background: Bronchial asthma is a serious threat to public health of chronic diseases worldwide. Although the awareness and diagnosis and treatment of asthma in the past 10 years have a leap in development, but its prevalence and mortality continued to show a rising trend, almost 300 million people with asthma. A large number of pathological studies confirmed that asthmatic airways there are not only inflammatory cell infiltration, and there are varying degrees of structural changes in the airway wall, airway reconstruction, mainly for inflammatory cell infiltration of airway smooth muscle (ASM) hypertrophy and hyperplasia Which occupies a very important position in the airway remodeling proliferation of airway smooth muscle cells (ASMC), which is considered to be intractable asthma pathological basis and closely associated with airway hyperresponsiveness and drug efficacy. Have been reported in recent years, angiotensin Ⅱ and its type I receptor may be involved in asthmatic ASMCs proliferation [2,3]. But its mechanism is not very clear. Of this study was to investigate the intervention effect of angiotensin II proliferation of airway smooth muscle cells (HASMCs) and angiotensin II type I receptor antagonist, and angiotensin II receptor (AT1R, AT2R) and transforming growth factor β1 (TGF-β1) mRNA expression changes from cellular and molecular level to explore whether the inhibition of airway smooth muscle remodeling effect and mechanism of angiotensin II type I receptor antagonist. Objective: The effects of angiotensin II type I receptor antagonist on airway smooth muscle cell proliferation and its mechanism. METHODS: Cultured human airway smooth muscle cells (HASMCs), angiotensin II (AngII) and AngII type I receptor antagonist valsartan to intervene, methyl thiazolyl tetrazolium blue (MTT) Trace colorimetry Determination of the HASMCs growth rate, flow cytometry the HASMCs cell cycle, respectively, using real-time quantitative PCR (Real time PCR) detection and Western blot, HASMCs angiotensin II receptor mRNA and protein expression; real-time quantitative PCR (Real time PCR) detection of transforming growth factor-β1 (TGF-β1) mRNA changes. Results: (1) MTT method. Measurement: of AngII HASMCs after stimulation of cell growth rate was significantly higher (P lt; 0.05), of AngII valsartan group was significantly lower than the rate of cell growth AngII group (P lt; 0.05); (2 ) flow cytometry: AngII stimulation of HASMCs significantly higher than the proportion of S phase of the cell cycle (P lt; 0.05), the proportion of S phase of the cell cycle of AngII valsartan group below AngII group (P lt; 0.05); (3 ) AngII stimulation of HASMCs, AT1R and AT2R expression were higher; that of AngII valsartan group AT1R expression was significantly lower than the AngII group (P lt; 0.05) of angiotensin Ⅱ type 2 receptor was no significant difference (P gt; 0.05); (4) AngII stimulation of HASMCs the TGF-β1mRNA after expression was significantly higher than that in the control group (P lt; 0.05), of AngII valsartan group the TGF-β1mRNA expression levels lower than the the AngII group of (P lt; 0.05). Conclusion: Angiotensin II type I receptor antagonists inhibit the proliferation of airway smooth muscle, and its mechanism of action may be to inhibit the expression of AT1R, lowered the level of TGF-β1.

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