本文選題：呼吸窘迫綜合征 + 雌二醇　； 參考：《中國全科醫(yī)學》2014年27期

【摘要】：目的探討17β-雌二醇介導的PI3K/AKT/SGK1信號通路對小鼠急性呼吸窘迫綜合征(ARDS)的保護作用及其對肺泡上皮鈉離子通道(ENaC)的調控。方法 40只雄性C57B/L6小鼠隨機分為對照組(control組)、模型組(LPS組)、17β-雌二醇治療組(E2組)、渥曼青霉素干預組(wortmannin組),每組10只。蘇木素-伊紅(HE)染色觀察肺組織病理改變并進行肺損傷評分;血氣分析動脈血氧分壓(PaO2)變化;肺濕干比(W/D)檢測肺水腫的嚴重程度;BCA法檢測肺泡灌洗液(BALF)中總蛋白含量;酶聯免疫吸附試驗(ELIAS)法檢測BALF中白介素(IL)-1β、腫瘤壞死因子α(TNF-α)水平及髓過氧化物酶(MPO)活性;反轉錄聚合酶鏈式反應(RT-PCR)法檢測各亞基ENaC mRNA表達;Western blotting法檢測AKT、SGK1磷酸化水平及各亞基ENaC蛋白表達水平變化。結果小鼠氣管內注射脂多糖(LPS)造模后,LPS組肺損傷評分為(4.2±0.2)分,E2組為(2.7±0.5)分,wortmannin組為(3.9±0.3)分,差異有統計學意義(F=46.07,P=0.000);其中E2組較LPS組降低,wortmannin組較E2組升高(P0.05)。4組不同時間PaO2比較有差異(F=188.148,P=0.000)。4組小鼠肺組織W/D,BALF中總蛋白含量,IL-1β、TNF-α水平,MPO活性,α-、β-、γ-ENaC的mRNA表達水平,α-、β-、γ-ENaC蛋白表達及p-AKT、p-SGK1表達水平比較有差異(P0.05);其中與control組比較,LPS組、E2組、wortmannin組W/D、BALF中總蛋白含量、IL-1β、TNF-α水平、MPO活性升高,α-、β-、γ-ENaC的mRNA表達水平降低(P0.05);與E2組比較,LPS組、wortmannin組W/D、BALF蛋白含量、IL-1β、TNF-α水平、MPO活性升高,α-、β-、γ-ENaC蛋白表達水平及p-AKT、p-SGK1表達水平降低(P0.05)。結論 17β-雌二醇可通過快速激活PI3K/AKT/SGK1信號通路介導的轉錄后調控機制上調ENaC表達,從而對小鼠ARDS肺水腫發(fā)揮保護作用。
[Abstract]:Objective to investigate the protective effect of 17 尾 -estradiol mediated PI3K/AKT/SGK1 signaling pathway on acute respiratory distress syndrome (ARDS) in mice and its regulation on alveolar epithelial sodium channel (ENAC). Methods Forty male C57B/L6 mice were randomly divided into control group (n = 10), control group (n = 10) and control group (n = 10). The pathological changes of lung tissue were observed by hematoxylin-eosin (HEH) staining and lung injury score was evaluated. The changes of arterial partial pressure of oxygen (Pao _ 2) were analyzed by blood gas analysis. The severity of pulmonary edema was detected by WR / D and the total protein content in alveolar lavage fluid (BALF) was detected by BCA method. Enzyme linked immunosorbent assay (Elisa) was used to detect the level of IL-1- 尾, TNF- 偽 and the activity of myeloperoxidase (MPO) in BALF. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of ENaC mRNA of each subunit. Western blotting was used to detect the phosphorylation level of AKT-1 SGK1 and the changes of ENaC protein expression in each subunit. Results after endotracheal injection of lipopolysaccharide (LPS), the lung injury score of LPS group was 4.2 鹵0.2) and that of E2 group was 2.7 鹵0.5). The score of wortmannin group was 3.9 鹵0.3). There were significant differences in the content of total protein IL-1 尾 -TNF- 偽, the mRNA expression of 偽 -, 尾 -, 緯 -ENaC, 偽 -, 尾 -, 緯 -ENAC protein expression and the expression of 偽 -, 尾 -, 緯 -ENaC protein in lung tissue of WR DBALF of mice in E _ 2 group compared with E _ 2 group, P0.054.The difference of total protein content in lung tissue of WR / DBALF was statistically significant (P < 0.01), and the mRNA expression level of wortmannin group was lower than that of LPS group compared with that of E _ 2 group. There were significant differences in PaO2 content in lung tissue of WR / DBALF group compared with that of E _ 2 group. Compared with control group, the total protein content of WR 尾 -TNF- 偽 increased and the mRNA expression level of 偽 -, 尾 -, 緯 -ENAC decreased P0.05a. Compared with E2 group, the level of WR / DBALF protein and the activity of IL-1 尾 TNF- 偽 increased in LPS group and E2 group, respectively, and the activity of IL-1 尾 -TNF- 偽 increased in LPS group compared with that in LPS group (P < 0 05), and the expression of 偽 -, 尾 -, 緯 -ENAC protein in WR / DBALF group was significantly increased than that in LPS group (P < 0 05), while the expression of 偽 -, 尾 -, 緯 -ENAC protein in WR / DBALF group was significantly higher than that in LPS group (P < 0 05). The expression level of 偽 -, 尾 -, 緯 -ENaC protein and p-AKTna-p-SGK1 protein decreased significantly (P 0.05). Conclusion 17 尾 -estradiol can up-regulate the expression of ENaC through the mechanism of rapid activation of PI3K/AKT/SGK1 signaling pathway, and thus play a protective role against ARDS pulmonary edema in mice.
【作者單位】： 重慶醫(yī)科大學附屬第二醫(yī)院呼吸內科;
【基金】：國家自然科學基金資助項目(81270141)
【分類號】：R563.8;R-332

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