Abstract
Acute lung injury (ALI) is the common and clinically severe complication. Dexmedetomidine (DEX) can protect against lipopolysaccharide (LPS)-induced ALI through anti-apoptosis, anti-inflammatory and immune regulatory actions. It is well documented that major causes of LPS-induced ALI are endoplasmic reticulum stress (ERS) and abnormally elevated CHOP. Moreover, XBP-1 can enhance CHOP expression. XBP-1S can aggravate ERS and XBP-1 U can repress ERS. By querying Starbase, miR-135a-5p interacts with XBP-1 and lncRNA MALAT1 sponges miR-135a-5p. It has been reported that MALAT1 interference markedly promoted the apoptosis of pulmonary microvascular endothelial cells in ALI rats by activating TLR4/NF-κB pathway. miR-135a-5p inhibitor remarkably alleviated LPS-induced A549 cell injury through suppressing cell apoptosis. In the present work, LPS was dripped into the nasal cavity of SD rats to establish the rat model of ALI and LPS was also applied to stimulate BEAS-2B cells to imitate ALI in vitro. Then, the pathology, lung function indexes, levels of inflammatory factors, apoptosis of lung tissues in SD rats and apoptotic level of BEAS-2B cells were measured, so as to confirm whether upregulation of lncRNA MALAT1 was able to suppress ERS, thus enhancing the protective effect of DEX against ALI. Herein, overexpression of lncRNA MALAT1 strengthened the remission effects of DEX on LPS-triggered ALI, severe pulmonary edema, inflammatory response and cell apoptosis of lung tissues in SD rats and reinforced the anti-apoptosis effect of DEX on LPS-stimulated BEAS-2B cells. Mechanically, lncRNA MALAT1 enhanced the protective effect of DEX against ALI by downregulating the ratio of XBP-1S/XBP-1U to repress ERS.