高脂摄入上调肺组织CYP 4A1表达缓解丰宫并殖吸虫感染所致大鼠肺损伤  

High⁃fat intake alleviates lung injury induced by Paragonimus proliferus in⁃fection in rats through up⁃regulating CYP 4A1 expression in lung tissues

作　　者：刘思奇 王晴晴 王卫群 吴磊 马志强 王霖 常国楫 丁洁 华丽娟 陈华憶 李生浩 王文林 LIU Siqi;WANG Qingqing;WANG Weiqun;WU Lei;MA Zhiqiang;WANG Lin;CHANG Guoji;DING Jie;HUA Lijuan;CHEN Huayi;LI Shenghao;WANG Wenlin(Department of Hepatology,Clinical Center for Infectious Diseases of Yunnan Province/The Third People’s Hospital of Kunming,Kunming,Yunnan 650041,China;Department of Pathogen Biology,Faculty of Basic Medicine,Kunming Medical University,Kunming,Yunnan 650504,China;Changpo Laboratory,Clinical Center for Infectious Diseases of Yunnan Province/The Third People’s Hospital of Kunming,Yunnan Province,China)

机构地区：[1]云南省传染性疾病临床医学中心/云南省昆明市第三人民医院肝病综合科,云南昆明650041 [2]昆明医科大学基础医学院病原生物学教研室,云南昆明650504 [3]云南省传染性疾病临床医学中心/云南省昆明市第三人民医院长坡检验科,云南昆明650041

出　　处：《中国血吸虫病防治杂志》2023年第2期171-176,共6页Chinese Journal of Schistosomiasis Control

基　　金：国家自然科学基金(82260408);云南省科技厅基础研究专项(202101AT070054);云南省昆明市卫健委卫生科研课题(2022-03-08-011,2022-03-08-005)。

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 m RNA(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。Objective To explore the improvements of high⁃fat intake on lung injury induced by Paragonimus proliferus infec⁃tion in rats,and to preliminarily explore the mechanisms underlying the role of cytochrome P4504A1(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 infec⁃tion 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 opti⁃cal 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 P4504A1(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 alle⁃viated 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 alveoli⁃tis 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 t

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 

分 类 号：R383.23[医药卫生—医学寄生虫学]