柚皮苷对百草枯致大鼠肺损伤保护作用的研究  

Study on the protective effect of naringin on paraquat-induced lung injury in rats

作　　者：姚梦雅 刘超[2] 孙兆瑞[2] 黄昌保 张炜[2] 杨志洲[2] 任艺[2] 韩小琴[2] 聂时南[2] Yao Meng-ya;Liu Chao;Sun Zhao-rui;Huang Chang-bao;Zhang Wei;Yang Zhi-zhou;Ren Yi;Han Xiao-qin;Nie Shi-nan(Wannan Medical College,Wuhu 241002,China)

机构地区：[1]皖南医学院研究生院,安徽芜湖241002 [2]东部战区总医院(原南京军区南京总医院)急诊医学科,江苏南京210002 [3]皖南医学院戈矶山医院,安徽芜湖241001

出　　处：《中国急救医学》2022年第3期255-259,共5页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金面上项目(82172182);江苏省社会发展面上项目(BE2017720)。

摘　　要：目的探讨柚皮苷在百草枯(PQ)诱导的大鼠肺损伤过程中的保护作用及其机制。方法将30只雄性SD大鼠随机均分为三组:空白对照组、百草枯组(百草枯20 mg/kg,ip)和百草枯+柚皮苷组(百草枯20 mg/kg,ip;2 h后柚皮苷100 mg/kg,ip),给药3 d后处死大鼠,收取肺组织和血液标本。测定肺湿/干质量比(W/D)与肺组织羟脯氨酸(HYP)含量,行肺组织切片及HE染色;测定大鼠动脉血氧分压(PaO_(2))与二氧化碳分压(PaCO_(2));检测丙二醛(MDA)含量、髓过氧化物酶(MPO)活性及超氧化物歧化酶(SOD)活性;通过ELISA检测肺组织中炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)与肿瘤坏死因子-α(TNF-α)的含量;通过qRT-PCR检测肺纤维化相关的转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)和基质金属蛋白酶2(MMP2)的mRNA表达水平。结果与百草枯组比较,百草枯+柚皮苷组大鼠肺组织病理损伤显著减轻,W/D值显著降低,HYP含量显著减少,血PaO_(2)升高,PaCO_(2)降低,差异均有统计学意义(P<0.05)。同时,百草枯+柚皮苷组大鼠肺组织MDA含量和MPO活性降低,SOD活性显著升高,炎性因子IL-1β、IL-6及TNF-α的表达水平显著降低,肺纤维化相关细胞因子TGF-β1、CTGF和MMP2的mRNA水平显著下调,差异均有统计学意义(P<0.05)。结论柚皮苷在百草枯诱导的大鼠肺损伤过程中可发挥抗氧化、抗炎与抗纤维化作用,从而减轻肺损伤并改善肺功能。Objective To explore the protective role and mechanism of naringin on paraquat-induced lung injury in rats.Methods Thirty male SD rats were randomly and equally divided into three groups:control group,paraquat group(paraquat 20 mg/kg,ip)and paraquat+naringin group(paraquat 20 mg/kg,ip;naringin 100 mg/kg,ip 2 hours after the paraquat).Three days after administration,the rats were executed,the lungs and blood specimens were collected,the lung wet/dry weight ratio(W/D)and hydroxyproline(HYP)content were measured.The lung tissue section and HE staining were performed.The arterial partial pressure of oxygen(PaO_(2))and partial pressure of carbon dioxide(PaCO_(2))were tested.The malondialdehyde(MDA)content,myeloperoxidase(MPO)activity and superoxide dismutase(SOD)activity in lung tissues were determined.The inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in lung tissues were tested by ELISA.The mRNA expression levels of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF)and matrix metalloproteinase 2(MMP2)which were associated with lung fibrosis were measured by qRT-PCR.Results Compared with the paraquat group,the lung histopathological damage of the paraquat+naringin group was significantly reduced,the lung W/D ratio was decreased(P<0.05),HYP content was also reduced(P<0.05),blood PaO_(2) was increased(P<0.05)and PaCO_(2) was decreased(P<0.05).In addition,in paraquat+naringin group,the MDA content and MPO activity in lung tissues were decreased(P<0.05),SOD activity was increased significantly(P<0.05),the expression of inflammatory factors including IL-1β,IL-6 and TNF-αwere significantly decreased(P<0.05).The mRNA levels of lung fibrosis-related cytokines including TGF-β1,CTGF and MMP2 were downregulated(P<0.05).Conclusions Naringin exerted antioxidant,anti-inflammatory and anti-fibrotic effects during paraquat-induced lung injury in rats,thereby reducing lung injury and improving lung function.

关 键 词：柚皮苷 百草枯 肺损伤 氧化应激 

分 类 号：R285.5[医药卫生—中药学]