Lv Q
Department of Respiratory, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
Eur Rev Med Pharmacol Sci. 2016 Sep;20(18):3920-3929.
In order to seek an effective strategy for clinical treatment of acute lung injury (ALI), we are committed to explore the effect of combination therapy of glucocorticoid and hyaluronic acid on acute lung injury caused by an endotoxin (LPS) and its mechanism.
Adult male Sprague-Dawley (SD) rats were divided randomly into 5 groups: normal group (n=8); LPS group (n=8); dexamethasone +LPS group (DXMS group, n=8); hyaluronic acid+ LPS group (HA group, n=8); dexamethasone +hyaluronic acid +LPS group (DXMS+HA group, n=8). Firstly, SD rat model with acute lung injury induced by LPS was established, and injected corresponding drugs according to the plan. Then, the expression of TNF-a, IL-8, IL-10, ICAM-1 and total protein were measured by ELISA, and the HE staining was used for detected the pathological change in lung tissue. Subsequently, the water content, dry and wet ratio and permeability in lung tissues of SD rats was assayed. Finally, the expression level of the glucocorticoid receptor (GR) was detected by RT-PCR, and activation of p-p38MAPK was determined by Western blotting.
The results showed that concentration of IL-8, IL-10 and ICAM-1 was significantly increased in BALF after LPS injection, and the results from HE staining showed it had widespread inflammation. However, lung structures in SD rats with inhalation lung injury were improved significantly after the injection of dexamethasone and hyaluronic acid, and the Pa02/Fi02, blood pressure and Cdyn were also increased. Moreover, lung water content, the ratio of wet and dry lung, and lung permeability index (LPI) was decreased after having treated the SD rats with a combination of dexamethasone and hyaluronic acid, and the apoptosis index was also decreased in the rats with LPS-induced ALI. Our data also suggested that TNF-α, IL-8, IL-10, intercellular cell adhesion molecule-1 (ICAM-1) and total protein was significantly declined in bronchoalveolar lavage fluid (BALF) of rats with LPS-induced acute lung injury after treated the SD rats with a combination of dexamethasone and hyaluronic acid. In addition, the data also implied that anti-inflammatory effect by inhibiting the activation of p38MAPK signal pathway induced by LPS through enhancement of the activity of GR, to further analyze the mechanism of the effect of combination therapy with dexamethasone and hyaluronic acid on acute lung injury in SD rats.
LPS-induced ALI in SD rats is relieved after treatment with a combination of dexamethasone and hyaluronic acid. In the process of its function, activated GR can represent anti-inflammatory effect and protect the lung tissue by inhibiting the activation/phosphorylation of p38MAPK, while hyaluronic acid can enhance micro-environment of alveolar tissue.
为寻求急性肺损伤（ALI）临床治疗的有效策略，致力于探讨糖皮质激素与透明质酸联合治疗对内毒素（LPS）所致急性肺损伤的影响及其机制。
成年雄性Sprague-Dawley（SD）大鼠随机分为5组：正常组（n = 8）；LPS组（n = 8）；地塞米松+LPS组（DXMS组，n = 8）；透明质酸+LPS组（HA组，n = 8）；地塞米松+透明质酸+LPS组（DXMS+HA组，n = 8）。首先，建立LPS诱导的SD大鼠急性肺损伤模型，并按计划注射相应药物。然后，采用ELISA法检测TNF-α、IL-8、IL-10、ICAM-1及总蛋白的表达，HE染色检测肺组织病理变化。随后，测定SD大鼠肺组织的含水量、干湿比及通透性。最后，采用RT-PCR检测糖皮质激素受体（GR）的表达水平，Western blotting检测p-p38MAPK的激活情况。
结果显示，注射LPS后BALF中IL-8、IL-10和ICAM-1浓度显著升高，HE染色结果显示有广泛炎症。然而，注射地塞米松和透明质酸后，吸入性肺损伤SD大鼠的肺结构明显改善，Pa02/Fi02、血压和Cdyn也升高。此外，地塞米松和透明质酸联合处理SD大鼠后，肺含水量、肺干湿比及肺通透性指数（LPI）降低，LPS诱导的ALI大鼠的凋亡指数也降低。我们的数据还表明，地塞米松和透明质酸联合处理SD大鼠后，LPS诱导的急性肺损伤大鼠支气管肺泡灌洗液（BALF）中TNF-α、IL-8、IL-10、细胞间黏附分子-1（ICAM-1）和总蛋白显著下降。此外，数据还暗示通过增强GR的活性抑制LPS诱导的p38MAPK信号通路的激活发挥抗炎作用，以进一步分析地塞米松和透明质酸联合治疗对SD大鼠急性肺损伤作用的机制。
地塞米松和透明质酸联合治疗可缓解SD大鼠LPS诱导的ALI。在其作用过程中，活化的GR可通过抑制p38MAPK的激活/磷酸化发挥抗炎作用并保护肺组织，而透明质酸可改善肺泡组织的微环境。
