Study the effects of tanshinone IIA on angiotensin II-induced rat thoracic aortic vascular smooth muscle cell proliferation

• Main Authors: Yao-chih Yang, 楊堯智
• Other Authors: Tzu-Hurng Cheng
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/64591226397244886680

碩士 === 中國醫藥大學 === 生物科技學系碩士班 === 100 === Recent evidence suggests that angiotensin II （Ang II） plays an important part in atherosclerosis and cardiovascular disease. Ang II, a potent vasoconstrictor, has been studied extensively for its role in stimulating abnormal proliferation of vascular smooth muscle cells （VSMCs）. The relevant literature indicates that Ang II can turn on the synthesis of the very potent vasoconstrictor peptide endothelin-1 （ET-1）. ET-1 has been shown to mediate the growth-promoting effect of Ang II and thus play an important role in cardiovascular disease. Ang II-mediated signal events likely to be important in VSMCs are the increase of cellular reactive oxygen species （ROS）, the following phosphorylation of extracellular signal-regulated kinases （ERK） and expression of endothelin-1 （ET-1）. As widely studies, tanshinone IIA （Tan IIA） extracted from Salvia miltiorrhiza （Danshen）, a popular medicinal herb used in traditional Chinese medicine. Literatures indicate that it has exhibit a variety role on cardiovascular activity. However, the effects of Tan IIA on Ang II-induce VSMCs proliferation are not well understood. Therefore, the present study was set to evaluate the effect and determine the mechanisms of Tan IIA on Ang II-induced VSMCs proliferation. In the present study, we used rat thoracic aortic smooth muscle cell line A7r5 to investigate mechanisms mediating Ang II-stimulated VSMC proliferation. The cells were preincubated with Tan IIA and then treated with Ang II to determine the cell viability, ROS production, ERK phosphorylation, ET-1 mRNA expression, which were measured by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTT） assay, flow cytometry, western blotting assay and reverse transcription polymerase chain reaction （RT-PCR）, respectively. Our results demonstrate that Tan IIA significantly reduced Ang II-induced cell proliferation. In addition, Tan IIA also significantly suppressed the production of ROS, ERK phosphorylation and ET-1 mRNA expression. In conclusion, our results suggest that Tan IIA significantly suppressed Ang II induced cell proliferation through the ROS, ERK phosphorylation, and ET-1 expression inhibition.