中国当代儿科杂志2011，Vol.13Issue(6)：503-508,6.
抑制Notch信号对血管紧张素Ⅱ诱导的肺血管重构的影响
Effect of inhibition of Notch signal on pulmonary vascular remodeling induced by angiotensin Ⅱ
摘要
Abstract
Objective It is known that Notch signal is very important to vascular remodeling during the process of embryonic development, vessel repair and tumor growth, but there are few studies about pulmonary vascular remodeling in pulmonary hypertension. This study was to explore the effect of inhibiting Notch signal on pulmonary vascular remodeling induced by angiotensin Ⅱ. Methods Vessel strips taken from healthy Wistar rats were co-cultured with extrogenous angiotensin Ⅱ and the potent smooth muscle cell proliferation stimulators for 7 days. Vascular wall thickness, proliferating cell nuclear antigen (PCNA) positive cell rate and caspase-3 positive cell rate were examined in vessel strips. Then some vessel strips were cultured with angiotensin Ⅱ and γ-secretase inhibitor DAPT, a Notch signaling inhibitor for 7 days. The levels of Notch 1 to 4 receptor and HERP1/2 mRNA were ascertained by FQ-PCR. Results Angiotensin Ⅱ stimulation in the cultured normal pulmonary arteries resulted in an increase in the vascular medial thickness by nearly 50％ , and a significant increase in the PCNA positive cell rate and a decrease in the caspase-3 positive cell rate. DAPT treatment did not result in the alterations of Notch 1 to 4 receptor levels, but decreased remarkably HERP1 and HERP2 mRNA expression. DAPT treatment also decreased angiotensin Ⅱ -induced vascular medial thickness and PCNA positive cell rate and increased caspase-3 positive cell rate. Conclusions Inhibiting Notch signal by γ-secretase inhibitor may lead to the suppression of pulmonary vascular remodeling induced by angiotensin Ⅱ , suggesting that the inhibition of Notch signal pathway might be a novel strategy for the treatment of pulmonary hypertension.关键词
Notch信号/血管紧张素/肺/血管重构/大鼠Key words
Notch signal/ Angiotensin/ Pulmonary/ Vascular remodeling/ Rats分类
医药卫生引用本文复制引用
乔莉娜,许红波,石坤,周同甫,华益民,刘瀚曼..抑制Notch信号对血管紧张素Ⅱ诱导的肺血管重构的影响[J].中国当代儿科杂志,2011,13(6):503-508,6.基金项目
国家自然科学基金(NO.30700913). （NO.30700913）
