Endoplasmic Reticulum Stress in Heat- and Shake-Induced Injury in the Rat Small Intestine.
Endoplasmic Reticulum Stress in Heat- and Shake-Induced Injury in the Rat Small Intestine.
复制标题
热和震动引起的大鼠小肠损伤中的内质网应激
DOI：
10.1371/journal.pone.0143922
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Xia Z
中科院分区：
文献类型：
--
作者：
Yin P;Xu J;He S;Liu F;Yin J;Wan C;Mei C;Yin Y;Xu X;Xia Z
我们研究了热应激和震动应激对大鼠小肠损伤的机制。18只SD大鼠随机分为对照组和应激3d组，应激组在35℃、60r/min的旋转平台上连续3d，每天应激2 h。应激后空肠苏木精-伊红染色切片显示绒毛尖端上皮细胞脱落，固有层外露。细胞凋亡在绒毛顶端增多，并延伸至基底膜。光镜下可见微绒毛变短变稀，核膜内陷，核膜间隙增大，内质网明显肿胀。基因芯片分析评估了93个与细胞凋亡、内质网应激和自噬相关的差异表达基因。相关基因来自基因本体论(GO)和京都基因和基因组百科全书(KEGG)数据库。有41个基因参与了细胞凋亡的调控，15个基因与自噬有关，11个基因对内质网应激有反应。KEGG认为，细胞的凋亡途径、丝裂原活化蛋白激酶(MAPK)信号通路、哺乳动物雷帕霉素靶标(MTOR)信号通路以及自噬的调控都涉及到这些信号通路。Caspase3(Caspase3)、Caspase12(Caspase12)和微管相关蛋白1轻链3(LC3)在绒毛顶端显著增加，mTOR降低，磷酸化AKT(P-AKT)减少。内质网应激参与并诱导热应激和震动应激后大鼠肠损伤的自噬和凋亡。生物信息学分析将有助于确定应激诱导的小肠损伤的潜在机制。
We investigated the mechanisms underlying damage to rat small intestine in heat- and shake-induced stress. Eighteen Sprague-Dawley rats were randomly divided into a control group and a 3-day stressed group treated 2 h daily for 3 days on a rotary platform at 35°C and 60 r/min. Hematoxylin and eosin-stained paraffin sections of the jejunum following stress revealed shedding of the villus tip epithelial cells and lamina propria exposure. Apoptosis increased at the villus tip and extended to the basement membrane. Photomicrographs revealed that the microvilli were shorter and sparser; the nuclear envelope invaginated and gaps in the karyolemma increased; and the endoplasmic reticulum (ER) swelled significantly. Gene microarray analysis assessed 93 differentially expressed genes associated with apoptosis, ER stress, and autophagy. Relevant genes were compiled from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Forty-one genes were involved in the regulation of apoptosis, fifteen were related to autophagy, and eleven responded to ER stress. According to KEGG, the apoptosis pathways, mitogen-activated protein kinase(MAPK) signaling pathway, the mammalian target of rapamycin (mTOR) signaling pathway, and regulation of autophagy were involved. Caspase3 (Casp3), caspase12 (Casp12), and microtubule-associate proteins 1 light chain 3(LC3) increased significantly at the villus tip while mTOR decreased; phosphorylated-AKT (P-AKT) decreased. ER stress was involved and induced autophagy and apoptosis in rat intestinal damage following heat and shake stress. Bioinformatic analysis will help determine the underlying mechanisms in stress-induced damage in the small intestine.