Upregulation of the tight junction protein occludin: effects on ventilation-induced lung injury and mechanisms of action.
Upregulation of the tight junction protein occludin: effects on ventilation-induced lung injury and mechanisms of action.
复制标题
DOI：
10.1186/1471-2466-14-94
复制
发表时间：
2014-05-29
影响因子：
3.1
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Liu M;Gu C;Wang Y
Occludin是一种紧密连接蛋白，在维持肺上皮屏障的完整性中起重要作用；然而，其在通气性肺损伤中的作用尚未探讨。在这里，我们测量了occludin在不同潮气量下的表达。我们的研究表明，急性肺损伤使occludin水平显著降低，肺泡通透性增加。选取体重250 ~ 300 g的健康Wistar大鼠30只（雌性15只，雄性15只），随机分为5组（每组n = 6）：对照组（C组）、低潮容组（L组）、低潮容+ PKC抑制剂组（L + P组）、高潮容组（H组）和高潮容+ PKC抑制剂组（H + P组）。对照组大鼠气管切开，不作任何特殊处理。L + P组和h + P组大鼠于麻醉前1 h肌内注射PKC抑制剂（双吲哚酰马来酰亚胺I， 0.12 mg/kg）。机械通气后处死大鼠。采集肺组织标本。光学显微镜下观察肺病理变化，测定肺干湿重比。免疫组化和Western blotting检测occludin蛋白水平。HE染色和免疫组化结果显示occludin主要位于肺泡上皮细胞和部分肺泡内皮细胞。高潮气量组肺损伤和肺泡水肿较低潮气量组严重。与低潮气量组相比，高潮气量组大鼠Occludin表达降低，PKC激活增加。大鼠经PKC抑制剂预处理后，高潮气量通气引起的肺水肿减少。机械通气可激活PKC信号通路，紧密连接蛋白参与该通路。occludin上调可减轻通气所致肺损伤。
Occludin, a tight junction protein, plays an important role in maintaining the integrity of the lung epithelial barrier; however, its role in ventilation-induced lung injury has not been explored. Here, we measured the expression of occludin with different tidal volumes. Our study indicated that the level of occludin was significantly decreased and alveolar permeability was increased owing to acute lung injury. Thirty healthy Wistar rats (15 female, 15 male) weighing 250–300 g, were randomly divided into 5 groups (n = 6 in each group): a control group (group C), a low tidal volume group (group L), a low tidal volume + protein kinase C(PKC) inhibitor group (group L + P), a high tidal volume group (group H) and a high tidal volume + PKC inhibitor group (group H + P). Tracheas of rats in the control group underwent incision without any special treatment. The other four groups were mechanically ventilated for 4 h. The rats in groups L + P and H + P were treated with a PKC inhibitor (bisindolylmaleimide I, 0.12 mg/kg) by intramuscular injection 1 h before anesthesia. Rats were sacrificed after mechanical ventilation. Specimens of lung tissues were harvested. Lung pathological changes were observed using an optical microscope, and lung wet/dry weight ratio was measured. The occludin protein level was assayed by immunohistochemistry and Western blotting. HE staining and immunohistochemistry results showed that occludin was mainly located in alveolar epithelial cells and some alveolar endothelial cells. The lung injury and alveolar edema were more serious in high tidal volume groups than in low tidal volume groups. Occludin expression was reduced and PKC activation was increased in rats in the high tidal volume groups compared with rats in the low tidal volume groups. Rats that were pretreated with the PKC inhibitor had less pulmonary edema induced by the high tidal volume ventilation. Mechanical ventilation can activate the PKC signaling pathway and tight junction proteins participate in this pathway. Up-regulation of occludin can reduce ventilation-induced lung injury.
登录
查看更多内容
影响因子：
4.8
作者：
Seth, Ankur;Sheth, Parimal;Rao, Radhakrishna
通讯作者：
Rao, Radhakrishna
影响因子：
24.3
作者：
Ricard, JD;Dreyfuss, D;Saumon, G
通讯作者：
Saumon, G
DOI：
10.1152/ajplung.00048.2011
发表时间：
2011-08-01
影响因子：
4.9
作者：
Wang, Yuelan;Minshall, Richard D.;Hu, Guochang
通讯作者：
Hu, Guochang
DOI：
10.1152/ajplung.1997.273.6.l1242
发表时间：
1997-12-01
影响因子：
4.9
作者：
Hinman, LE;Beilman, GJ;Sammak, PJ
通讯作者：
Sammak, PJ
DOI：
10.1007/s11596-012-1044-0
发表时间：
2012-12-01
影响因子：
--
作者：
Wang, Yuelan;Dai, Guofeng;Liu, Yang
通讯作者：
Liu, Yang