Hypoxia Affects Autophagy in Human Umbilical Vein Endothelial Cells via the IRE1 Unfolded Protein Response

Objective:The purpose of this study was to investigate the role of the unfolded protein response,specifically the inositol-requiring enzyme 1(IRE1)signaling pathway,in hypoxia-induced autophagy in human umbilical venous endothelial cells(HUVECs).Methods:The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting,qRT-PCR and confocal microscopy.Further,we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro.Finally,we examined the function of IRE1 in local blood vessels through animal models,Results:Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs.Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals.Conclusion:Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.

由区域震及远震波形得到中国溧阳1974和1979年地震的断裂机制——在以断层为界的盆地下构造逆转的证据

中国东部1974年和1979年溧阳地震是两次中强地震,但属破坏性地震。第一次地震(M_s=5.5)于1974年4月22日发生在人口密集的地区。第二次地震(M_s=5.7)于1979年7月9日几乎在同一地区发生。两次地震震中位于两断层的交汇附近,在晚中生代到晚第三纪的沉积拉张盆地内。本文利用2°和90°之间的长周期P波、SH波及短周期远震PD波波形,确定两次地震具有逆冲分量的走滑震源机制。这一机制与较早用P波初动解得到的结果有明显不同。后者得到两次地震的走滑分量和正滑分量。本次研究的结果是,1974年地震机制是走向126°,倾角71°,滑动角33°。震源深度、地震矩和应力降分别为12km,8.4×10^(23)dyne-cm(1dyne=10^(-5)N)和41bar。1979年地震机制是走向41°,倾角64°,滑动角147°。震源深度、地震矩和应力降分别为7.5km,1.6×10^(24)dyne-cm和152bar。地震学资料与实地调查表明,1974年地震是WNW走向断层破裂所致。1979年地震的断层面很难求解。溧阳地震的逆冲断裂,在中国东部的较大地震中是很少见的。这可能表明在现代的E-W到ENE-WSW向压应力场作用下,构造盆地下方断层重新被激活,而且发生逆转。