吸入上转换纳米颗粒对小鼠肺肝均有一过性损害

Inhalation of upconversion nanoparticles does transient damage to the mouse liver and lung

背景:有体外实验对上转换纳米颗粒的毒性进行了研究,但有关上转换纳米颗粒体内毒性的研究不多。目的:观察吸入上转换纳米颗粒对小鼠各脏器的毒性作用。方法:切开36只气管Balb/c小鼠后,随机分为3组,实验组经气管滴入上转换纳米颗粒28 mg/kg,对照组经气管滴入等量生理盐水,假手术组不滴入任何物质。术后1 d、1周、2周,检测肺、肝及肾功能,观察肺、肝、肾、心组织形态学变化。结果与结论:(1)肺、肝、肾功能功能:术后1 d,实验组酸碱度值低于对照组和假手术组(P<0.05),谷丙转氨酶水平高于对照组和假手术组(P<0.05);假手术组术后1 d的氧分压高于实验组和对照组(P<0.05)。3组间术后1,2周的氧分压、谷丙转氨酶水平比较差异无显著性意义。3组间术后不同时间点的二氧化碳分压、肾功能比较差异无显著性意义;(2)肺组织病理:术后1 d,实验组增生和炎症反应最严重,肺泡腔变形,血管充血;对照组增生和炎症反应明显,肺泡腔受挤压,肺泡间隔增宽;假手术组小鼠肺泡结构和形态正常,无炎症细胞浸润。术后1,2周时,实验组和对照组肺部病变随时间延长逐渐减轻;(3)肝组织病理:术后1 d,实验组肝细胞肿胀,空泡变性现象较重;对照组肝细胞中度水肿,有空泡变性出现;假手术组肝细胞轻度水肿,少量空泡变性;术后2周时,各组小鼠肝脏形态均恢复正常;(4)肾、心组织病理:各组心、肾组织结构未发生明显变化;(5)结果表明:表明上转换纳米颗粒对小鼠肺、肝均有一过性的损害。

BACKGROUND：Lots of in vitro experiments have explored the toxicity of upconversion nanoparticles, but its toxicity in vivo is little reported. OBJECTIVE：To investigate the toxicity of upconversion nanoparticles in mouse organs. METHODS：After tracheotomy, 36 Balb/c mice were randomly divided into three groups, fol owed by instil ed with 28 mg/kg upconversion nanoparticle （experimental group）, the same volume of normal saline （control group）, and nothing （sham operation group）, respectively. The functional changes of the lung, liver and kidney were detected at 1 day, 1 and 2 weeks postoperatively, and meanwhile, the morphological changes of the lung, liver, kidney, and heart were observed. RESULTS AND CONCLUSION：At 1 day postoperatively, the pH values in the experimental group were lower than those in the control and sham operation groups （P〈0.05）, while the glutamic-pyruvic transaminase level was higher than that in the control and sham operation groups （P〈0.05）. The oxygen partial pressure in the sham operation group was higher than that in the other two groups at 1 day postoperatively （P〈0.05）. The oxygen partial pressure and glutamic-pyruvic transaminase level did not significantly differ among groups at 1 and 2 weeks postoperatively. The carbon dioxide differential pressure and kidney function showed no significant differences among groups at different time points after surgery. At postoperative 1 day, in the experimental group, hyperplasia and inflammation were most obvious, distorted alveolar cavity and congestion of blood vessels were visible. In the control group, obvious hyperplasia and inflammation were found, the alveolar cavity was crimped and the gap between alveoli was broadened. The sham operation group had normal alveoli with no inflammations. Lung lesions in the experimental and control groups became mild with time at postoperative 1 and 2 weeks. One day postoperatively, hepatocyte swel ing and vacuolar degeneration were severer in the experimental group. Moderate hepatocyte swel ing and vacuolar degeneration occurred in the control group. The sham operation group showed mild hepatocyte swel ing and vacuolar degeneration. The morphology of the liver in each group returned to normal at 2 weeks postoperatively. Fortunately, the heart and kidney structure showed no overt changes in each group. These findings suggest that upconversion nanoparticles cause transient damage to the mouse lung and liver.