1. 毕业设计（论文）的内容和要求

本课题采用sugen 5416/缺氧大鼠模型诱发肺动脉高压，尾静脉注射二甲双胍，利用he切片，观察二甲双胍对大鼠肺血管重构的影响。

培养大鼠肺动脉平滑肌细胞，缺氧处理后，加入二甲双胍，运用mtt、brdu、edu、流式、western blotting等实验方法检测其对细胞增殖的影响。

利用基因芯片技术检测二甲双胍处理后的肺血管组织上调和下调的基因，及其可能的信号通路 前期进行文献调查，设计实验方案，采购药品，建立并验证大鼠模型，测定二甲双胍对细胞增殖的影响，最后检测二甲双胍处理后的组织的相关基因，发现可能的信号通路。

2. 参考文献

References 1. Thompson A A Roger, Lawrie Allan. Targeting Vascular Remodeling to Treat Pulmonary Arterial Hypertension. 燭rends Mol Med, 2017, 23(1): 31-45.#8194; 2. Liu Yun, Cao Yonggang, Sun Shuyang, et al. Transforming growth factor-beta1 upregulation triggers pulmonary artery smooth muscle cell proliferation and apoptosis imbalance in rats with hypoxic pulmonary hypertension via the PTEN/AKT pathways. 營nt J Biochem Cell Biol, 2016, 77(Pt A): 141-54.? 3. Ravi Yazhini,燬elvendiran Karuppaiyah,燤eduru Sarath,爀t al. Dysregulation of PTEN in cardiopulmonary vascular remodeling induced by pulmonary hypertension. Cell Biochem Biophys,#8194;2013, 67(2): 363-72.? 4. 躰l?Murat,燘alta 猠vket,燗rslan Zekeriya,爀t al. The effect of metformin on cardiac fibrosis via differentiation of cardiac fibroblasts. Cardiology,#8194;2015, 130(1): 52-3.? 5. Burl?Adriana K,燣obato N鷅ia S,燜ortes Zuleica B, et al. Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats. 營nt J Cardiol#8194;2013, 165(3): 483-7.? 6. Fu Yong-Nan,燲iao Han,燤a Xiao-Wei,爀t al. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation. Acta Pharmacol Sin,#8194;2011, 32(7): 879-87. 7. Xiao Han,燤a Xiaowei,燜eng Wei, et al. Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway. Cardiovasc Res,#8194;2010, 87(3): 504-13.?

3. 毕业设计（论文）进程安排

2018/01-2018/02 建立sugen 5416/缺氧大鼠模型 2018/02-2018/04 验证模型是否成功，HE染色实验、免役组化实验；培养大鼠肺动脉平滑肌细胞 2018/05-2018/06 完成MTT、BrdU、EDU、流式、western blotting等实验验证二甲双胍对细胞增殖的影响 2018/06- 整理数据，撰写论文