Department of Emergency Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Department of Infectious Disease, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, China.
Biomed Pharmacother. 2018 Oct;106:1404-1411. doi: 10.1016/j.biopha.2018.07.111. Epub 2018 Jul 24.
The mechanism in lung injury caused by acute organophosphate pesticide poisoning (AOPP) and an effective treatment remains unclear. We aim to clarify how the inflammatory lung injury caused by AOPP might be modulated by Xuebijing (XBJ) injection.
AOPP-induced lung injury model was induced by dichlorvos (DDVP) subcutaneous administration in rats and XBJ injection was administered by intraperitoneal injection after DDVP challenge. The effects of XBJ injection were assessed by lung histopathological analysis and lung injury scores, lung wet-to-dry weight ratios (WDR) and oxygenation, differential immune cell count in bronchoalveolar lavage fluid (BALF), IL-6 and TNF-α levels in blood, the levels of TLR4 and NF-κB proteins in lung tissue and blood acetylcholinesterase (AChE) activity.
DDVP administration resulted in damage of lung histopathology and lower PaO2/FiO2 ratios (P < 0.05), which were notably attenuated by XBJ injection (P < 0.05). Total cell, macrophage, and neutrophils count in BALF and TNF-α and IL-6 levels in blood were significantly increased after DDVP exposure (P < 0.05), which were notably ameliorated by XBJ injection (P < 0.05). TLR4 and NF-κB protein in lung tissue expression after DDVP challenge were markedly increased (P < 0.05), and they were substantially downregulated by XBJ injection (P < 0.05). In addition, blood AChE activity was significantly decreased by DDVP administration (P < 0.05), however, there was no significant improvement after XBJ injection.
XBJ injection prevents DDVP poisoning induced lung injury by attenuating the inflammatory response. The protective effect appears to be mediated through downregulation of the TLR4 and NF-κB expression.
急性有机磷农药中毒（AOPP）导致的肺损伤的机制和有效的治疗方法仍不清楚。我们旨在阐明血必净（XBJ）注射液如何调节 AOPP 引起的炎症性肺损伤。
通过对大鼠皮下给予敌敌畏（DDVP）诱导 AOPP 诱导的肺损伤模型，并在 DDVP 攻击后通过腹腔注射给予 XBJ 注射液。通过肺组织病理学分析和肺损伤评分、肺湿重与干重比（WDR）和氧合、支气管肺泡灌洗液（BALF）中差异免疫细胞计数、血液中 IL-6 和 TNF-α水平、肺组织和血液中 TLR4 和 NF-κB 蛋白水平以及血液乙酰胆碱酯酶（AChE）活性评估 XBJ 注射液的作用。
DDVP 给药导致肺组织病理学损伤和 PaO2/FiO2 比值降低（P < 0.05），而 XBJ 注射显著减轻了这种损伤（P < 0.05）。DDVP 暴露后 BALF 中的总细胞、巨噬细胞和中性粒细胞计数以及血液中的 TNF-α和 IL-6 水平显著增加（P < 0.05），而 XBJ 注射显著改善了这种情况（P < 0.05）。DDVP 攻击后肺组织中 TLR4 和 NF-κB 蛋白的表达明显增加（P < 0.05），而 XBJ 注射显著下调了它们的表达（P < 0.05）。此外，DDVP 给药显著降低了血液中的 AChE 活性（P < 0.05），但 XBJ 注射后没有显著改善。
XBJ 注射液通过减轻炎症反应来预防 DDVP 中毒引起的肺损伤。这种保护作用似乎是通过下调 TLR4 和 NF-κB 的表达来介导的。
