目的 考察右美托咪定（Dex）對脂多糖（LPS）誘導的大鼠急性肺損傷（ALI）的影響，并探討可能與PI3K/Akt信號通路改變的相關機制。方法 將80只SD大鼠根據(jù)建模方法隨機分為5組：對照組、模型組、Dex低劑量組、Dex高劑量組、Dex+LY294002組，建模24 h時處死并分離肺組織，觀察組織病理切片，檢查肺水腫程度及微血管通透性，采用Western blotting法檢測Akt及其磷酸化蛋白以及線粒體凋亡信號相關蛋白的表達水平，檢查線粒體細胞色素C、膜電位及ATP含量，并用電鏡觀察線粒體形態(tài)，采用流式細胞術檢測肺組織細胞凋亡情況，采用DCFH-DA探針熒光顯微鏡法檢測細胞內(nèi)的活性氧（ROS）水平。結果 LPS滴注24 h后，病理切片表現(xiàn)有明顯的ALI特征，Dex在50 μg/kg劑量時可明顯改善LPS誘導的ALI病理特征；以對照組為參照，p-Akt（Thr308）與p-Akt（Ser473）的相對表達量模型組未發(fā)生明顯變化，Dex組則均顯著增高（P<0.001），在Dex+LY294002組的表達水平較Dex組顯著降低（P<0.001）；模型組的Bax與Bcl-2蛋白較對照組的相對表達量分別顯著升高與降低（P<0.001），Dex組分別降低與升高至接近對照組水平，Dex+LY294002組又分別回升與回降；對照組、模型組、Dex組、Dex+LY294002組的肺組織細胞凋亡率分別為2.4%、19.5%、6.7%、13.1%；各組的ROS水平變化與肺組織細胞凋亡情況一致性良好。結論 Dex可通過激活PI3K/Akt信號通路減輕LPS誘導的肺組織細胞凋亡及線粒體凋亡信號激活，繼而改善ALI，發(fā)揮肺保護作用。

Objective To investigate the effect of dexmedetomidine (Dex) on LPS-induced acute lung injury (ALI) in rats, and to explore the possible mechanism of PI3K/Akt signaling pathway changes. Methods Eighty SD rats were randomly divided into five groups:control group, model group, Dex low-dose group, Dex high-dose group and Dex + LY294002 group. After 24 h of modeling, the lung tissues were separated. Histopathological sections were observed to examine the degree of pulmonary edema and microvascular permeability. Western blotting was used to detect the expression of Akt, its phosphorylated protein and mitochondrial apoptotic signal-related protein. The levels of cytochrome C, membrane potential and ATP in mitochondria were examined. The morphology of mitochondria was observed by electron microscopy. The apoptosis of lung cells was detected by flow cytometry. The ROS level in cells was detected by DCFH-DA probe fluorescence microscopy. Results After 24 h of LPS infusion, the pathological sections showed obvious ALI characteristics. Dex could significantly improve the pathological characteristics of LPS-mediated ALI at the dose of 50 ug/kg. Compared with the control group, the relative expression of p-Akt (Thr308) and p-Akt (Ser473) did not change significantly in model group, but increased significantly in Dex group (P<0.05), and the expression level of p-Akt (Thr308) and p-Akt (Ser473) in Dex + LY294002 group was significantly lower than that in the Dex group (P<0.05). The relative expression of Bax and Bcl-2 protein in model group was significantly higher and lower than that in control group (P<0.05). The expression of Bax and Bcl-2 protein in Dex group was lower and higher than that in model group, while that in Dex +LY294002 group was higher and lower. The apoptotic rates of lung tissue in control group, model group, Dex group and Dex +LY294002 group were 2.4%, 19.5%, 6.7% and 13.1% respectively, the changes of ROS levels in each group were in good agreement with the apoptosis of lung cells. Conclusion Dex can alleviate LPS-mediated apoptosis of lung tissue and mitochondrial apoptosis by activating PI3K/Akt signaling pathway, and then improve ALI to play a protective role in lung.

R974

河南省醫(yī)學科技攻關計劃項目（2018020351）