木犀草素缓解双酚A诱导的小鼠卵巢毒性作用研究  

Effect of luteolin on bisphenol A-induced ovarian toxicity in mouse models

作　　者：张曦倩[1] 姚俐[1] 罗燕群[1] 易艳红[1] 董梅[1] 刘风华[1] Zhang Xiqian;Yao Li;Luo Yanqun;Yi Yanhong;Dong Mei;Liu Fenghua(Reproductive Center,Guangdong Maternal and Child Health Hospital,Guangzhou 511400,China)

机构地区：[1]广东省妇幼保健院生殖中心,广州511400

出　　处：《新医学》2020年第7期539-543,共5页Journal of New Medicine

基　　金：广东省中医药局中医药科研项目(20191038)。

摘　　要：目的观察木犀草素对双酚A诱导的小鼠卵巢毒性的缓解作用及初步探索p38丝裂原活化蛋白激酶(p38 MAPK)和细胞外信号调节蛋白激酶(ERK)是否参与其中。方法 32只昆明小鼠随机分为正常对照组、双酚A组、双酚A和木犀草素共处理组(共处理组)、木犀草素组,每组各8只,其中双酚A组以10 mg/(kg·d)的双酚A溶剂灌胃,共处理组依次以10 mg/(kg·d)的木犀草素溶剂和10 mg/(kg·d)的双酚A溶剂灌胃,木犀草素组以10 mg/(kg·d)的木犀草素溶剂灌胃,正常对照组以等体积玉米油灌胃;给药均持续4周。给药结束后取小鼠卵巢组织,检测各组小鼠卵巢组织中丙二醛水平、超氧化物歧化酶(SOD)及过氧化氢酶(CAT)活性的变化,并检测凋亡相关蛋白Caspase-3的活化片段(cleaved Caspase-3)、磷酸化p38 MAPK、磷酸化ERK蛋白表达。结果经双酚A处理后,小鼠卵巢组织丙二醛水平升高(P <0.05)、SOD和CAT活性降低(P <0.05)、cleaved Caspase-3蛋白相对表达量升高(P <0.05)、p38 MAPK和ERK的磷酸化水平升高(P <0.05);与双酚A单独处理相比,木犀草素与双酚A共处理后小鼠卵巢组织丙二醛水平降低(P <0.05)、SOD和CAT活性增高(P <0.05)、cleaved Caspase-3蛋白相对表达量降低(P <0.05)、而磷酸化p38 MAPK和ERK蛋白相对表达量降低(P <0.05)。木犀草素组与正常对照组各项指标比较差异均无统计学意义(P均>0.05)。结论木犀草素可有效缓解双酚A诱导的小鼠卵巢毒性作用,其可能与p38 MAPK和ERK信号通路的参与有关。Objective To evaluate the alleviating effect of luteolin on bisphenol A-induced ovarian toxicity in mouse models and to explore whether p 38 mitogen-activated protein kinase(p38 MAPK) and extracellular regulatory kinase(ERK) are involved in this process.Methods Thirty-two Kunming mice were randomly divided into 4 groups with 8 mice in each group:negative control group(NC),bisphenol A group(BPA),bisphenol A and luteolin co-treatment group(BPA+Lut),and luteolin group(Lut),respectively.The mice in the BP A group were administrated with BPA solvent at a dose of 10 mg/(kg·d),those in the BPA+Lut group were treated with 10 mg/(kg·d) luteolin solvent and 10 mg/(kg·d) BPA solvent in sequence,animals in the Lut group were administrated with 10 mg/(kg·d) luteolin solution and those in the negative control group were given with an equal volume of corn oil.The above drugs were administered by daily gavage for 4 consecutive weeks.After corresponding administrations,the ovarian tissues were collected.The changes in the activity of malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) were observed.The expression levels of apoptosis-related protein cleaved Caspase-3(cleaved Caspase-3),phosphorylated p38 MAPK and ERK proteins were quantitatively measured.Results MDA levels in the ovarian tissues were significantly increased after BPA treatment(P <0.05),while SOD and CAT activities were markedly reduced(both P<0.05).The expression level of cleaved Caspase-3 protein was significantly up-regulated(P<0.05),p38 MAPK and ERK phosphorylation levels were also significantly increased(both P <0.05).Compared with BPA treatment alone,co-treatment with luteolin and BPA significantly reduced the MDA levels(P <0.05),elevated the SOD and CAT activities(both P <0.05),and down-regulated the relative expression levels of cleaved Caspase-3,phosphorylated p38 MAPK and ERK proteins(all P <0.05).There was no significant difference between Lut and NC(all P> 0.05).Conclusion Luteolin can effectively alleviate BPA-induced ovarian toxicity

关 键 词：木犀草素 双酚A 细胞外信号调节蛋白激酶 P38丝裂原活化蛋白激酶 氧化损伤 

分 类 号：R285.5[医药卫生—中药学]