Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway

Acute myocardial ischaemia/reperfusion (MIR) injury leads to severe arrhythmias and has a high rate of lethality. In the present study, we aim to determine the effect of dexmedetomidine (Dex) on heart injury parameters following MIR surgery. We examined the effects of Dex on heart function parameters and infarct size following MIR surgery. Proinflammatory cytokines, oxidative products and anti‐oxidative enzymes in the myocardium were measured to evaluate the anti‐inflammatory and anti‐oxidative effects of Dex. The role of the adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK)/phosphatidylino‐sitol 3‐kinase (PI3k)/Akt/endothelial nitric oxide synthase (eNOS) pathway was investigated using their inhibitors. The alteration of haemodynamic parameters, histopathological results, and infarct size caused by MIR was attenuated by Dex. The interleukine‐1 beta (IL‐1β), IL‐6, tumour necrosis factor‐a (TNF‐α) and myeloperoxidase (MPO) were all significantly decreased. Anti‐oxidative enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were restored by Dex. Oxidative products8‐OHdG, MDA and protein carbonyl were all decreased by Dex (P<.05). Dex activated AMPK expression, eNOS and Akt phosphorylation. The influence of Dex on cardiac function was reversed by the inhibitors of the eNOS, AMPK and PI3K/Akt pathways. These results indicate that Dex protected the cardiac functional, histological changes, inflammation and oxidative stress induced by MIR. Our results present a novel signalling mechanism that Dex protects MIR injury by activating an AMPK/PI3K/Akt/eNOS pathway.     

Aliskiren improves endothelium‐dependent relaxation of thoracic aorta by activating PI3K/Akt/eNOS signal pathway in SHR

Aliskiren, a direct renin blocker, has been approved for the treatment of hypertension. However, the potential role of aliskiren on vascular endothelial function in spontaneously hypertensive rats (SHR) remains unclear. In the present study, male SHRs at 12 weeks of age were orally administrated 30 mg/kg per day or 60 mg/kg per day aliskiren. After a 4‐week treatment, aliskiren showed a significant effect on the reduction of blood pressure at a dosage of 60 mg/kg per day, but not of 30 mg/kg per day. Moreover, both dosages of aliskiren improved endothelium‐dependent relaxation, reduced dihydroethidium fluorescence intensity, decreased level of malondialdehyde but heightened total antioxidant capacity and superoxide dismutase activity in thoracic aorta in SHR. Aliskiren also markedly increased expression of p85α, an important subunit of phosphatidylinositol 3 kinase (PI3K), enhancing phosphorylation of protein kinase B (Akt) at Ser473 and endothelial nitric oxide synthase (eNOS) at Ser1177, as well as cyclic guanosine‐3′5′‐monophosphate (cGMP, a sensitive index of biological activity of nitric oxide) concentration. Furthermore, both anti‐oxidative and endothelium protective effects of aliskiren were diminished when PI3K was inhibited in vivo. The data presented here indicates that, aliskiren improves endothelium‐dependent relaxation of thoracic aorta in SHR, predominantly through attenuating oxidative stress and activation of the PI3K/Akt/eNOS pathway. These data might propose novel strategies to prevent and improve vascular endothelial dysfunction.     

Intermedin alleviates the inflammatory response and stabilizes the endothelial barrier in LPS-induced ARDS through the PI3K/Akt/eNOS signaling pathway

Inflammatory storms and endothelial barrier dysfunction are the central pathophysiological features of acute respiratory distress syndrome (ARDS). Intermedin (IMD), a member of the calcitonin gene-related peptide (CGRP) family, has been reported to alleviate inflammation and protect endothelial cell (EC) integrity. However, the effects of IMD on ARDS have not been clearly elucidated. In the present study, clinical ARDS data were used to explore the relationship between serum IMD levels and disease severity and prognosis, and we then established a model to predict the possibility of hospital survival. Mouse models of ARDS and LPS-challenged endothelial cells were used to analyze the protective effect and underlying mechanism of IMD. We found that in patients with ARDS, increased serum IMD levels were associated with reduced disease severity and increased rates of hospital survival. IMD alleviated the LPS-induced inflammatory response by decreasing proinflammatory cytokines, NF-κB p65 expression and NF-κB p65 nuclear translocation. In addition, IMD stabilized the endothelial barrier by repairing adherens junctions (AJs), cytoskeleton and capillary leakage. IMD exerted protective effects against ARDS on pulmonary endothelial cells, at least partly, through PI3K/Akt/eNOS signaling, while IMD’s anti-inflammation effect was mediated through an eNOS-independent mechanism. Our study may provide new therapeutic insight for ARDS treatment.     

Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigated the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20 μM) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-κB and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.     

Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500 mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400 mg PU/kg intragastrically once daily) for 75 days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.     

PI3K/Akt信号通路与肝纤维化

PI3K/Akt信号通路为细胞内重要信号传导通路之一,在促进细胞增殖、抑制凋亡的过程中发挥重要作用。PI3K/Akt信号通路与肝纤维化的发生、发展密切相关。通过干预PI3K/Akt信号通路,研究肝纤维化的发病机制和药物治疗是有意义的途径。该文就PI3K/Akt信号通路的构成、转导途径及其在肝纤维化中的作用作一综述。     

Salidroside protects PC12 cells from MPP-induced apoptosis via activation of the PI3K/Akt pathway

Oxidative stress plays an important role in the pathogenesis of Parkinson’s disease (PD). Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., can exert potent antioxidant properties. In this study, we investigated the protective effects, and the possible mechanism of action, of SAL against 1-methyl-4-phenylpyridinium (MPP⁺)-induced cell damage in rat adrenal pheochromocytoma PC12 cells. Pretreatment of PC12 cells with SAL significantly reduced the ability of MPP⁺ to induce apoptosis in a dose and time-dependent manner. SAL significantly and dose-dependently inhibited MPP⁺-induced chromatin condensation and MPP⁺-induced release of lactate dehydrogenase by PC12 cells. SAL enhanced Akt phosphorylation in PC12 cells, and the protective effects of SAL against MPP⁺-induced apoptosis were abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation. These findings suggest that SAL prevents MPP⁺-induced apoptosis in PC12 cells, at least in part through activation of the PI3K/Akt pathway.     

Luteolin inhibits apoptosis and improves cardiomyocyte contractile function through the PI3K/Akt pathway in simulated ischemia/reperfusion

Luteolin, a naturally occurring polyphenol flavonoid, has demonstrated to exert myocardial protection effects. However, the mechanisms have not been fully elucidated. In the present study, we investigated whether luteolin pretreatment was associated with cardioprotection in a rat ischemia/reperfusion (I/R) model. Luteolin significantly not only restored contractility of the left ventricle, but also reduced the infarct size and lactate dehydrogenase leakage during I/R. In addition, luteolin pretreatment significantly improved cardiomyocyte shortening amplitude, decreased the apoptotic rate, upregulated Bcl-2 expression, downregulated Bax expression and raised the Bcl-2/Bax ratio under a simulated ischemia/reperfusion (SI/R) condition. Moreover, luteolin pretreatment increased protein kinase B (Akt) phosphorylation, phospholamban phosphorylation and the expression of sarcoplasmic reticulum calcium ATPase following SI/R. The phosphoinositide 3-kinase (PI3K)/Akt pathway is one of the most important intracellular survival signal pathways. To determine whether luteolin-induced cardioprotection was mediated by the PI3K/Akt pathway, we utilized the PI3K inhibitor LY294002. Inhibition of Akt activity markedly abolished luteolin-induced positive contraction and inhibition of apoptosis in SI/R cardiomyocytes. These results showed that luteolin inhibits apoptosis and improves cardiomyocyte contractile function at least partly through the PI3K/Akt pathway in SI/R.     

XJP-1 protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by inhibiting NADPH oxidase subunit expression and modulating the PI3K/Akt/eNOS pathway

Endothelial apoptosis triggered by oxidized low-density lipoprotein (ox-LDL) can accelerate the progression of endothelial dysfunction in atherosclerosis. (±)7,8-Dihydroxy-3-methyl-isochromanone-4 (XJP-1) is a natural phenolic compound derived from banana peel. In the present study, we investigated the anti-apoptotic effect of XJP-1 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL and explored underlying mechanisms. Our results showed that in the presence of ox-LDL, XJP-1 significantly attenuated ox-LDL-mediated cytotoxicity, apoptosis, caspase-3 activation, reactive oxygen species (ROS) generation, and NADPH oxidase subunit (p22phox and p47phox) expression in HUVECs. In addition, the anticytotoxic and anti-apoptotic effect of XJP-1 was partially inhibited by a PI3K inhibitor (LY294002), an Akt inhibitor (SH-6), a specific eNOS inhibitor (l-NAME) and a NADPH oxidase inhibitor (DPI). In exploring the underlying mechanisms of XJP-1 action, we found that XJP-1 eliminated ox-LDL-induced dephosphorylation of Akt and eNOS in a dose-dependent manner. However, XJP-1 alone upregulation of Akt and eNOS phosphorylation were blocked by LY294002 and SH-6. Moreover, XJP-1 increased NO production, but this effect was abolished by LY294002, SH-6 and l-NAME. The inhibition of ox-LDL-induced endothelial dysfunction by XJP-1 is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.     

阿托伐他汀通过激活PI3K/Akt/mTOR信号转导而促进神经元突起生长

目的探讨阿托伐他汀(Ato)对体外培养大鼠皮质神经元突起生长促进作用的信号转导机制。方法 取培养7 d大脑皮质神经元,分为Ato 10μmo.lL-1作用48 h组和阻断剂+Ato组,先分别加入阻断剂PD98059 50μmo.l L-1、LY294002 30μmol.L-1、曲西立滨(TCBN)2.5μmol.L-1和西罗莫司(雷帕霉素,Rapa)100 nmo.l L-1作用1 h,再加入Ato共同作用48 h。应用倒置相差显微镜观察神经元突起生长状况;Western印迹法检测磷酸化的磷酸肌醇依赖激酶1(PDK1)、磷酸化蛋白激酶B(Akt)、磷酸化西罗莫司靶蛋白(mTOR)、磷酸化的核糖体S6激酶(p70S6K)和磷酸化的真核翻译起始因子4E结合蛋白1(p-4E-BP1)的表达。结果 形态学观察结果显示,Ato 10μmo.lL-1组可明显促进突起生长,表现为突起总长度增加、一级突起数目增多、末端分支数增多及胞体面积增大。PD98059,LY294002,TCBN和Rapa均可阻断Ato对神经元突起生长的促进作用。Western印迹结果显示,Ato 10μmo.lL-1可显著上调p-PDK1,p-Akt(Ser473),p-mTOR,p-p70S6K和p-4E-BP1蛋白表达水平(P<0.01)。LY294002可显著阻断Ato引起的p-PDK1,p-Akt(Ser473)蛋白表达水平增加(P<0.01)。TCBN可显著阻断Ato引起的p-mTOR蛋白表达水平增加(P<0.01)。Rapa可明显阻断Ato引起的p-p70S6K和p-4E-BP1蛋白表达水平增加(P<0.01)。结论 Ato对体外培养皮质神经元突起发育的促进作用可能与激动MEK/ERK信号转导通路有一定的关系,主要可能与通过激活PI3K/Akt/mTOR信号转导通路有关。     

Cyanidin-3-rutinoside increases glucose uptake by activating the PI3K/Akt pathway in 3T3-L1 adipocytes

In this study, the effect of cyanidin-3-rutinoside (C3R) on glucose uptake by 3T3-L1 adipocytes was studied. C3R significantly increased glucose uptake, which was associated with enhanced plasma membrane glucose transporter type 4 (PM-GLUT4) expression in 3T3-L1 adipocytes. The potentiating effect of C3R on glucose uptake and PM-GLUT4 expression was related to enhanced phosphorylation of insulin receptor substrate 1 (IRS-1) and Akt, as well as augmented activation of phosphatidylinositol-3-kinase (PI3K) in the insulin signaling pathway. C3R induced glucose uptake was inhibited only by the PI3K inhibitor, but not by an AMPK inhibitor in 3T3-L1 adipocytes. Therefore, C3R likely up-regulates glucose uptake and PM-GLUT4 expression in 3T3-L1 adipocytes by activating the PI3K/Akt pathways.     

玉郎伞查尔酮调控PI3K/Akt信号通路抗心肌缺血/再灌注损伤的作用及机制研究

目的探讨玉郎伞查尔酮(YLSC)调控PI3K/Akt信号通路抗心肌缺血/再灌注损伤的作用及机制。方法 40只♂SD大鼠随机分为5组:假手术组、模型组、YLSC组、YLSC+PI3K抑制剂wortmannin组(YLSC+WM组)、PI3K抑制剂wortmannin组(WM组),每组8只。除假手术组外,其它各组大鼠均结扎冠状动脉左前降支制备心肌缺血模型,缺血30 min,再灌注120 min。实验结束后,采用比色法测定大鼠血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)及一氧化氮(NO)水平,ELISA法测定血清肿瘤坏死因子(TNF-α)的含量,Western blot法检测心肌组织中总Akt(t-Akt)、磷酸化Akt(p-Akt)及自噬相关蛋白LC3-Ⅱ的表达,FQ-PCR法分析内皮型一氧化氮合酶(eN OS)、凋亡因子caspase-3及自噬相关基因Beclin1的表达量变化。结果与I/R组比较,YLSC组CK-MB、LDH以及TNF-α血清含量明显降低,NO水平升高,Beclin1、caspase-3及LC3-Ⅱ的表达量均明显下降,同时Akt的磷酸化水平与eN OS mR NA表达增加,上述各项指标差异具有统计学意义(P<0.05),而上述变化能够被PI3K/Akt信号通路的特异性阻断剂wortmannin所阻断,且其差异具有统计学意义(P<0.05)。结论 YLSC通过激活PI3K/Akt信号通路抑制缺血/再灌注所致的心肌细胞凋亡和过度自噬,从而发挥对心肌缺血/再灌注损伤的保护作用。     

Alpha-lipoic acid activates eNOS through activation of PI3-kinase/Akt signaling pathway

BackgroundLipoic acid (LA) exerts therapeutic effects on cardiovascular diseases. However, the mechanisms underlying these therapeutic effects remain elusive. Endothelial nitric oxide synthase (eNOS) plays a critical role in cardiovascular homeostasis. LA was shown to potently activate PI3-kinase/Akt pathway, and the latter is critical in the regulation of eNOS activity. In the present study, we test the hypothesis that LA improves endothelial function through PI₃-kinase/Akt-mediated eNOS activation.Methods and ResultsWestern blot analysis showed that LA time- and dose-dependently induced phosphorylation of Akt and eNOS in human umbilical vein endothelial cells (HUVECs). Both PI₃-kinase and Akt inhibitors abolished LA-induced eNOS phosphorylation, indicating that LA induces eNOS phosphorylation through the PI₃-kinase/Akt pathway. This increase in eNOS phosphorylation was paralleled by an increase in NO release by HUVECs, supporting its relevance in eNOS activity regulation. Myograph analysis revealed that LA relaxed phenylephrine-induced contraction. Endothelium removal and NOS inhibition by L-NAME abolished this vasodilator action of LA, and Akt but not AMPK inhibition significantly reduced the vasodilator action of LA, indicating that it is mediated by PI₃-kinase/Akt pathway-dependent activation of eNOS. Consistent with in vitro results, intraperitoneal injection with LA significantly increased plasma nitrite and nitrate levels in C57Bl/6j mice.ConclusionsLA activates eNOS through a PI3-kinase/Akt signaling pathway-dependent mechanism, offering a potential molecular basis for the therapeutic effects of LA on cardiovascular diseases.     

PI3K/Akt/mTOR pathway as a target for cancer therapy

The PI3K/Akt/mTOR pathway regulates several normal cellular functions that are also critical for tumorigenesis, including cellular proliferation, growth, survival and mobility. Components of this pathway are frequently abnormal in a variety of tumors, making them an attractive target for anti-cancer therapy. Inhibition of mTOR in patients with cancer became more feasible after the development of rapamycin analogs with improved pharmacologic properties. The promising activity of these agents in early clinical trials has led to the development of ongoing phase III trials in renal cell carcinoma and breast cancer. Future studies are needed to identify the patients most likely to benefit from this form of therapy, and to define its role in combination with chemotherapy, hormones and growth factor inhibitors.     

甲状腺腺瘤与PI3K/Akt信号转导途径的关系

目的 探讨甲状腺腺瘤疾病与磷脂酰肌醇3激酶／蛋白激酶B（P13K／Akt）信号转导途径之间的关系。方法 外科手术中获取19例单发结节型甲状腺腺瘤组织及瘤旁组织,采用RT-PCR技术及免疫组化方法检测腺瘤及瘤旁组织中P13K、ARt的表达。结果 （1）甲状腺腺瘤组织中P13K、ARt基因的mRNA表达水平均显著高于瘤旁组织（P〈0．01）;（2）免疫组化P13K、ARt染色均分布于细胞胞浆中,腺瘤组织中P13K、ARt的平均积分光度值均显著高于瘤旁组织（P〈0．01）。结论 P13K／Akt信号转导途径功能异常可能参与甲状腺腺瘤增殖的病理生理机制。     

PI3K/Akt/mTOR信号通路与结直肠恶性肿瘤

结直肠癌(colorectal cancer,CRC)是世界大多数地区最常见的恶性肿瘤之一。它的发展是一个多步骤过程,以改变正常细胞的分子信号为启动点,促进细胞发展,最终产生一种表型改变的恶性转化细胞。已有报道指出磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白[phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/the mammalian target of Rapamycin(mTOR),PI3K/Akt/mTOR]信号通路与结直肠恶性肿瘤产生有紧密的联系。也有报道证明约60%~70%的结直肠癌患者存在Akt信号的活化及PTEN的表达受损,进而说明PI3K/Akt/mTOR信号通路抑制药可以作为恶性肿瘤治疗的潜在靶点。近年来,PI3K/Akt/mTOR信号通路受到越来越多的关注,在不同的实验模型中利用针对这条通路的天然及合成药物来降低恶性肿瘤负荷。将近年来PI3K/Akt/mTOR信号通路在结直肠恶性肿瘤中的研究做一综述,并就今后结直肠恶性肿瘤中该通路可能的研究方向进行展望。     

辛伐他汀通过Akt/eNOS途径改善心肌梗死后急性期心功能

目的探讨辛伐他汀(simvastatin,Sim)对急性心肌梗死后心肌内源性抗氧化系统的影响及其潜在机制。方法应用结扎大鼠冠状动脉左前降支的方法模拟急性心肌梗死(AMI),随机分为心肌梗死组(MI)组和辛伐他汀组(Sim,20mg·kg-1·d-1),另设假手术组(Sham组)。Sim组连续灌胃7 d,MI组和Sham组给予等剂量的生理盐水灌胃。7 d后,观察心肌血流动力学参数变化;检测血脂及心肌坏死标记物肌钙蛋白I(c-Tn I)和乳酸脱氢酶(LDH)变化;ELISA法检测心肌抗氧化系统超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GP)水平。Western blot检测心肌p-Akt/p-e NOS蛋白表达变化。结果急性心肌梗死明显降低心肌血流动力学参数,增加血清c-Tn I和LDH水平,降低SOD及GP水平,降低p-Akt和p-e NOS蛋白表达。Sim组能明显改善急性期心功能恶化,减低血清c-Tn I和LDH水平,增加SOD及GP水平,增加p-Akt和p-e NOS蛋白表达。结论急性心肌梗死后早期应用Sim能明显改善心功能,增加心肌抗氧化系统活性,减少心肌坏死,这可能与提高p-Akt和p-e NOS蛋白表达有关。     

右美托咪定激活PI3K/Akt通路改善LPS诱导的大鼠急性肺损伤实验研究

目的 考察右美托咪定（Dex）对脂多糖（LPS）诱导的大鼠急性肺损伤（ALI）的影响,并探讨可能与PI3K/Akt信号通路改变的相关机制。方法 将80只SD大鼠根据建模方法随机分为5组：对照组、模型组、Dex低剂量组、Dex高剂量组、Dex+LY294002组,建模24 h时处死并分离肺组织,观察组织病理切片,检查肺水肿程度及微血管通透性,采用Western blotting法检测Akt及其磷酸化蛋白以及线粒体凋亡信号相关蛋白的表达水平,检查线粒体细胞色素C、膜电位及ATP含量,并用电镜观察线粒体形态,采用流式细胞术检测肺组织细胞凋亡情况,采用DCFH-DA探针荧光显微镜法检测细胞内的活性氧（ROS）水平。结果 LPS滴注24 h后,病理切片表现有明显的ALI特征,Dex在50 μg/kg剂量时可明显改善LPS诱导的ALI病理特征;以对照组为参照,p-Akt（Thr308）与p-Akt（Ser473）的相对表达量模型组未发生明显变化,Dex组则均显著增高（P<0.001）,在Dex+LY294002组的表达水平较Dex组显著降低（P<0.001）;模型组的Bax与Bcl-2蛋白较对照组的相对表达量分别显著升高与降低（P<0.001）,Dex组分别降低与升高至接近对照组水平,Dex+LY294002组又分别回升与回降;对照组、模型组、Dex组、Dex+LY294002组的肺组织细胞凋亡率分别为2.4%、19.5%、6.7%、13.1%;各组的ROS水平变化与肺组织细胞凋亡情况一致性良好。结论 Dex可通过激活PI3K/Akt信号通路减轻LPS诱导的肺组织细胞凋亡及线粒体凋亡信号激活,继而改善ALI,发挥肺保护作用。