Liu Jianyun, Liu Junling, Wang Hui, Bai Mingming
Department of Burn, Gansu Provincial Hospital Lanzhou 730000, Gansu Province, China.
Int J Clin Exp Pathol. 2019 Feb 1;12(2):576-583. eCollection 2019.
Celastrol (CEL) was shown to display anti-inflammatory properties, and played an important role in anti-apoptosis. There were inflammation mediated by cytokines and apoptosis distinctly in the progression of acute lung injury (ALI) burn-induced. This study was conducted to explore the role of CEL in ALI induced by burns. In order to induce burn injury, rats were exposed to a 92°C water bath for 18 seconds. After burn experiment, the Burn + Celastrol group received CEL, and vehicle (DMSO) was used to treat the rats from Burn + Vehicle group. And the Sham + Burn group received no treatment. Vascular protein leakage was detected by Evans blue (EB) concentration to evaluate the lung microvascular permeability. Then wet-to-dry lung weight ratio (W/D), and hematoxylin and eosin staining (H&E) were measured respectively to investigate interstitial edema, neutrophil recruitment, and histopathological changes in lung tissues burn-induced ALI. To explore the mechanism of action of CEL, we assessed levels of inflammatory cytokines by ELISA assay, TUNEL staining and western blotting. Then we detected apoptosis-related factors, including the amount of apoptotic cells, caspase-3 activity, and Bax or Bcl-xl, respectively. The pulmonary microvascular hyperpermeability, histopathological characteristics, and a high W/D were attenuated by CEL for burn-injury rats. The concentration of cytokines burn-induced ALI from tissues and serum were decreased by CEL. Furthermore, after CEL treatment, TUNEL-positive cells, the protein level of Bax and caspase-3 activity reduced, and the level of Bcl-xl in protein increased. In conclusion, in lung injury burn-induced, CEL has a positive effect on anti-inflammation and anti-apoptosis. Thus, CEL could be as a latent for the cure of ALI burn-induced.
雷公藤红素（CEL）具有抗炎特性，并在抗凋亡过程中发挥重要作用。在烧伤诱导的急性肺损伤（ALI）进展过程中，存在明显的细胞因子介导的炎症和凋亡。本研究旨在探讨CEL在烧伤诱导的ALI中的作用。为诱导烧伤损伤，将大鼠置于92°C水浴中18秒。烧伤实验后，烧伤+雷公藤红素组给予CEL，而烧伤+溶媒组用溶媒（二甲基亚砜）处理大鼠。假手术+烧伤组不接受任何处理。通过伊文思蓝（EB）浓度检测血管蛋白渗漏，以评估肺微血管通透性。然后分别测量肺湿重与干重比（W/D）以及苏木精-伊红染色（H&E），以研究烧伤诱导的ALI肺组织中的间质水肿、中性粒细胞募集和组织病理学变化。为探究CEL的作用机制，我们通过酶联免疫吸附测定（ELISA）、TUNEL染色和蛋白质印迹法评估炎症细胞因子水平。然后我们分别检测凋亡相关因子，包括凋亡细胞数量、半胱天冬酶-3活性以及Bax或Bcl-xl。CEL减轻了烧伤大鼠的肺微血管高通透性、组织病理学特征以及高W/D。CEL降低了烧伤诱导的ALI组织和血清中的细胞因子浓度。此外，CEL处理后，TUNEL阳性细胞、Bax蛋白水平和半胱天冬酶-3活性降低，而Bcl-xl蛋白水平升高。总之，在烧伤诱导的肺损伤中，CEL对抗炎和抗凋亡具有积极作用。因此，CEL有望成为治疗烧伤诱导的ALI的潜在药物。
