摘要
目的:探究小檗碱对乌拉坦诱导的肺癌模型小鼠的保护作用及对PI3K/AKT信号通路的调控作用。方法:将120只小鼠随机分为空白组,模型组,顺铂组和小檗碱高、中、低剂量组,每组20只。除空白组外,其他小鼠腹腔注射乌拉坦建立肺癌模型。空白组和模型组小鼠灌胃等量生理盐水;顺铂组和小檗碱高、中、低剂量组小鼠予以药物干预。实验期间记录小鼠的体质量、自主活动,计算肺癌发生率和肺肿瘤结节数,HE染色观察肺组织病理变化,ELISA试剂盒检测血清CEA、CA125含量,免疫组化检测肺组织EMT转化标志E-cadherin、N-cadherin蛋白阳性细胞百分比,Western blotting法检测肺组织PI3K、AKT、p-AKT蛋白表达水平。结果:与空白组比较,模型组小鼠的生存质量较差,肺癌发生率为100%,肺组织出现明显癌变,血清中CEA和CA125的含量增加,肺组织E-cadherin蛋白表达降低,N-cadherin蛋白表达增加,PI3K、AKT、p-AKT蛋白相对表达量增加,差异均有统计学意义(P<0.05)。与模型组比较,小檗碱可改善小鼠的生存质量,降低肺癌发生率和肺肿瘤结节数,肺组织形态显著改善,炎症细胞浸润减轻,血清CEA和CA125的含量降低,肺组织E-cadherin蛋白表达增加,N-cadherin蛋白表达降低,PI3K、AKT、p-AKT蛋白相对表达量降低,差异均有统计学意义(P<0.05),且呈剂量依赖性(P<0.05)。其中,小檗碱高剂量组各指标与顺铂组比较,差异无统计学意义(P>0.05)。结论:小檗碱对乌拉坦诱导的小鼠肺癌具有保护和改善作用,其机制可能与抑制PI3K/AKT信号通路的活化有关。
Objective:To explore the protective effect of berberine on urethane-induced lung cancer model mice and its regulation of PI3K/AKT signaling pathway.Methods:A total of 120 mice were randomly divided into blank group,model group,cisplatin group and berberine high-dose group,berberine medium-dose group,and berberine low-dose group,with 20 mice in each group.Except for the blank group,other mice were intraperitoneally injected with urethane to establish lung cancer models.Mice in the blank group and model group were given the same amount of normal saline.Mice in the cisplatin group and berberine high,medium and low-dose groups were given drug intervention.During the experiment,the body weight and autonomous activities of the mice were recorded,the incidence of lung cancer and the number of lung tumor nodules were calculated,and the pathological changes of lung tissue were observed by HE staining.The serum CEA and CA125 were detected by ELISA kit.The percentage of E-cadherin and N-cadherin protein positive cells were detected by immunohistochemistry.The expression levels of PI3K,Akt and p-Akt were detected by Western blotting.Results:Compared with the blank group,the quality of life of mice in the model group was poor,the incidence of lung cancer was 100%,the content of CEA and CA125 in serum was increased,the expression of E-cadherin in lung tissue was decreased,the expression of N-cadherin was increased,and the relative expression of PI3K,Akt and p-Akt protein was increased,the differences were statistically significant(P<0.05).Compared with the model group,berberine could improve the quality of life,reduce the incidence of lung cancer and the number of lung tumor nodules,significantly improve the morphology of lung tissues,reduce the inflammatory infiltration,reduce the content of serum CEA and CA125,increase the expression of E-cadherin,decrease the expression of N-cadherin,and decrease the expression of PI3K,Akt and p-Akt in the lung tissues.The effect of different d oses of berberine was dose-dependent(P<0.05).There was no significant difference between the berberine h igh-dose group and cisplatin group(P>0.05).Conclusion:Berberine can protect and improve the lung cancer induced by urethane in mice,and its mechanism may be related to inhibiting the activation of PI3K/Akt signaling pathway.
作者
谢育霞
姚志雪
黄文绯
曹罗元
XIE Yu-xia;YAO Zhi-xue;HUANG Wen-fei;CAO Luo-yuan(Ningde Hospital Affiliated to Ningde Normal University,Ningde Fujian 352100,China;Mindong Hospital of Ningde,Ningde Fujian 352000,China)
出处
《中医药导报》
2021年第7期42-46,共5页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
