卡托普利及氯沙坦对百草枯中毒大鼠肺纤维化和肺组织PlGF表达的影响  

The effect of captopril and Iosartan on paraquat-induced pulmonary fibrosis and PIGF expression in the lungs of rats

作　　者：郑敏辉[1] 戴木森 林立芳 

机构地区：[1]武警福建总队医院呼吸内科,福州350003 [2]福建医科大学省立临床学院 [3]福建省心血管病重点研究所

出　　处：《中华劳动卫生职业病杂志》2017年第9期656-662,共7页Chinese Journal of Industrial Hygiene and Occupational Diseases

摘　　要：目的探讨百草枯（PQ）中毒大鼠肺纤维化模型中胎盘生长因子（P1GF）的表达及卡托普利（Captopril）、氯沙坦（Losartan）对PQ中毒肺纤维化的干预作用。方法84只健康成年雌性SD大鼠随机分为对照组、单纯染毒组（PQ）、卡托普利治疗组和氯沙坦治疗组，每组分别观察7、14和28d。单纯染毒组和两组治疗组于实验开始一次性PQ（40mg／kg）灌胃染毒而对照组予以等量的生理盐水灌胃，而后两个治疗组每日分别予以卡托普利（60mg／kg）、氯沙坦（10mg／kg）灌胃，对照组和单纯染毒组则以等量生理盐水灌胃。取肺组织行半定量的病理组织学检查、羟脯氨酸测定，并利用RT—PCR和免疫组化方法测定P1GFmRNA和蛋白水平的表达。结果PO染毒后大鼠肺泡炎、肺纤维化程度积分明显增高，肺组织羟脯氨酸含量明显增高。卡托普利和氯沙坦治疗组大鼠肺泡炎、肺纤维化程度积分均较单纯染毒组减轻，7、14d时卡托普利和氯沙坦治疗组肺泡炎积分与PQ组的差异有统计学意义（P〈0．05）；28d时卡托普利和氯沙坦治疗组肺纤维化积分均与PQ组的差异有统计学意义（P〈0．05）。3个时点卡托普利治疗组、氯沙坦治疗组羟脯氨酸含量均较PQ组明显降低，差异有统计学意义（均P〈0．01）。PQ组肺组织P1GFmRNA表达明显增高，7、14、28d分别1．28±0．29、0．80±0．07、0．65±0．13，均高于对照组（0．10±0．01、0．10±0．01和0．10±0．01），3个时点两治疗组的P1GFmRNA表达均较PQ组降低，卡托普利治疗组分别为0．94±0．04、0．71±0．09、0．52±0．24、氯沙坦治疗组分别为0．80±0．12、0．66±0．11、0．51±0．03，7、14d两个治疗组P1GFmRNA与PO组的差异有统计学意义（均P〈0．05）。PQ组肺组织P1GF免疫组化阳性指数明显增高，均高于对照组，3个时点两治疗组的P1GF免疫组化阳性指数均较PQ组降低，7d时点Objective To investigate the dynamic expression of placenta growth factor（P1GF） in the lungs and its role in paraquat-induced pulmonary fibrosis and to evaluate the effect of ACEI captopril and AT （ 1 ）- receptor blocker losartan on paraquat-induced pulmonary fibrosis. Methods 84 adult healthy female Sprague- Dawley（SD） rats were randomly divided into four groups of different treatments designated as： Control, PQ alone （PQ）, captopril treatment, losartan treatment. Each group was divided into three subgroups of seven animals each. The animals were killed at either 7, 14 or 28 days after PQ administration. The rats in PQ group, treatment group were treated intragastrically （ig） with PQ （40 mg/kg） and the rats in control group were treated with the same dose of saline at the beginning of the experiment. The treatment group received Captopril （60 mg/kg ; ig） or Losartan （ 10 mg/kg ; ig） once a day respectively after PQ administration and the other two groups received saline. At the given timepoint, animals were sacrificed and lungs were harvested. A scmiquantitative assay of histological examination, hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of P1GF. Results Inflammatory cell infihration and fibrotic scores were more prominent in the model group, hydroxyproline contents in lung tissue were significantly increased after PQ administration compared to the control group. Captopril, losartan apparently attenuated the degree of lung injury and pulmonary fibrosis. On 7th, 14th days, the levels of alveolitis in the intervention groups were significantly alleviated as compared with the model group （P〈0.05）. On 28th days, the levels of pulmonary fibrosis in the intervention groups were significantly alleviated as compared with model group （P〈0.05）. The hydroxyproline contents in the intervention groups were significantly decreased as compared wit

关 键 词：百草枯 大鼠 肺纤维化 胎盘生长因子 

分 类 号：R595.4[医药卫生—内科学] R-332[医药卫生—临床医学]