乳腺增生病的中医证素研究

目的探讨胰岛素通过SGKl对LPS诱导的急性肺损伤状态下的钠离子通道的调节作用。方法30只雄性Wistar大鼠随机平均分为对照组（Control组）、治疗组（LPS＋Insulin组）和模型组（LPS组）每组10只。记录5个时间点（O、0．5、1、3、6h）大鼠的血糖水平，并使用胰岛素使LPS＋Insulin组大鼠血糖控制在1．5到4．5mmol／L。通过HE染色观察肺组织病理学改变；使用湿／干比（W／D）分析肺水肿程度；使用RT-PCR、Westernblot和免疫组织化学对a-ENac的表达进行测量；SGKl和磷酸-SGKl（phospho-SGKl）蛋白表达使用Westernblot进行定量分析。结果大鼠注射LPS后血糖明显上升并于3h达到最大值。LPS干预6h后大鼠肺损伤评分和w／D比值明显增加，a-ENaC表达量和磷酸化-SGKl水平明显下降，差异有显著统计学意义。同时发现，LPS＋Insulin组大鼠肺损伤评分和W／D比值较LPS组大鼠稍低，而α-ENaC表达量和磷酸化-SGKl水平较之升高，差异均有统计学意义（P〈0．05）。结论胰岛素可以有效减轻LPS诱导的大鼠ARDS导致的肺水肿，其机制可能与促进SGKl的活化后上调了ENaC的表达相关。该结果为应用胰岛素治疗肺水肿奠定了理论基础。

Insulin Promotes Epithelial Sodium Channel in LPS induced Acute Lung Injury via SGK1 Signaling Pathway

Objective To investigate the role of insulin on the regulation of ENaC via SGK1 in LPS-induced acute lung injury in rats. Methods Thirty male Wistar rats were randomly divided into three groups--Control group, LPS-I-In- sulin group and LPS group （n=10）. Blood glucose level of rats in five point-in-time（0,0.5h, 1h, 3h and 6 h）, was recorded with blood glucose level of LPS＋Insulin group rats on 1.5 to 4. 5mmol/L. HE staining was used to evaluate the pathological changes in lung. Wet to dry ratio （W/D） was included to measure the degree of lung edema. RT-PCR, Western blot and immunohistochemistry were used to measure expression of α-ENaC. Then, SGK1 and phosphorylated SGK1 were evaluated by Western blot as well. Results After 6h LPS injection, severe pathological changes, increased W/D, down-regulated α-ENaC expression and reduced phosphorylated SGK1/total SGK1 were found. However, compared with LPS group, pathological changes and W/D were significantly ameliorated, meanwhile, α-ENaC expression and phosphorylated SGK1/total SGK1 were notably increased in LPS＋Insulin group. Conclusion Our findings demonstrated that insulin up-regulates ENaC in vivo possibly resulting from activation of SGK1.