Abstract: Objective　To explore the improvements of high⁃fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improvements. Methods　SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high⁃fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high⁃fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high⁃fat diet. All rats were sacrificed 28 weeks post⁃infection, and serum samples and lung specimens were collected. Following hematoxylin⁃eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi⁃quantitative scoring. Serum interleukin⁃1β (IL⁃1β) and tumor necrosis factor alpha (TNF⁃α) levels were measured using enzyme⁃linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real⁃time PCR (qPCR) and Western blotting assays. Results　Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post⁃infection with P. proliferus in rats in the infection and high⁃fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high⁃fat diet group. The semi⁃quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high⁃fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL⁃1β [(151.586 ± 20.492)] pg/mL and TNF⁃α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL⁃1β: (103.226 ± 3.366) pg/mL; TNF⁃α: (144.807 ± 1.348) pg/mL] and the infection and high⁃fat diet group [IL⁃1β: (110.131 ± 12.946) pg/mL; TNF⁃α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high⁃fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion　High⁃fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up⁃regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Key words: Paragonimus proliferus, Cytochrome P450 4A1, High?fat diet, Lung injury, Rat

摘要： 目的　观察高脂摄入对丰宫并殖吸虫感染所致大鼠肺损伤的缓解作用，并初步探讨细胞色素P450酶4A1（cytochrome P450 4A1, CYP 4A1）在该过程中的作用。方法　将SD大鼠分为正常对照组（10只）、感染+普通饮食组（12只）、感染+高脂饮食组（12只）。正常对照组大鼠普通饮食喂养，不予其他任何处理；感染+普通饮食组、感染+高脂饮食组每只大鼠均经腹壁皮下注射8条丰宫并殖吸虫后尾蚴，随后分别给予普通饮食、高脂饲料喂养。饲养28周后处死3组大鼠，收集血清及肺组织。大鼠肺组织苏木素⁃伊红（HE）染色，光学显微镜下观察各组大鼠肺损伤程度，并进行肺泡炎半定量评分；采用酶联免疫吸附试验（ELISA）法检测大鼠血清中白细胞介素（IL）⁃1β和肿瘤坏死因子（TNF）⁃α浓度，通过实时定量PCR（qPCR）及Western blotting检测大鼠肺组织中CYP 4A1 mRNA和蛋白质表达水平。结果　丰宫并殖吸虫感染28周后与感染+普通饮食组相比，感染+高脂饮食组大鼠肺泡壁增厚、水肿、炎症细胞浸润情况较轻，未见肺泡实变；感染+普通饮食组肺泡炎半定量评分[（2.200 ± 0.289）分]显著高于正常对照组[（0.300 ± 0.083）分]和感染+高脂饮食组[（1.300 ± 0.475）分]（P均< 0.05），感染+普通饮食组大鼠血清IL⁃1β [（151.586 ± 20.492） pg/mL]和TNF⁃α [（180.207 ± 23.379） pg/mL]水平均显著高于正常对照组[（103.226 ± 3.366）、（144.807 ± 1.348） pg/mL]和感染+高脂饮食组[（110.131 ± 12.946）、（131.764 ± 27.831） pg/mL]（P均< 0.05），感染+普通饮食组大鼠肺组织中CYP 4A1 mRNA（3.00 ± 0.81）和蛋白表达水平（0.40 ± 0.02）均显著低于正常对照组（5.03 ± 2.05、0.84 ± 0.14）和感染+高脂饮食组（11.19 ± 3.51、0.68 ± 0.18）（P 均< 0.05）。结论　高脂摄入可能通过上调肺组织中CYP 4A1 mRNA及蛋白表达来缓解丰宫并殖吸虫感染所致大鼠肺损伤。

关键词: 丰宫并殖吸虫, 细胞色素P450酶4A1, 高脂饮食, 肺损伤, 大鼠