蒙古扁桃油对肺纤维化大鼠的保护作用研究  

Protective Effect of Amygdalus mongolica Oil Against Pulmonary Fibrosis in Rats

作　　者：李倩 白万富[1] 周红兵[1] 郝海梅 李想 常虹[1] 石松利[1,2] Li Qian;Bai Wanfu;Zhou Hongbing;Hao Haimei;Li Xiang;Chang Hong;Shi Songli(Baotou Medical College,Baotou 014060;Institute of Bioactive Substance and Function of Mongolian Medicine and Chinese Materia Medica,Baotou Medical College,Baotou 014060)

机构地区：[1]包头医学院药学院,包头014060 [2]包头医学院蒙中药活性物质与功能研究所,包头014060

出　　处：《中药药理与临床》2021年第4期90-96,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81760782、81641137);内蒙古自然科学基金项目(编号:2019MS 08189、2018LH03027);内蒙古自治区“草原英才工程”青年创新创业人才项目(一层次人选,编号:Q2017046);内蒙古自治区第十一批“草原英才”人才项目(内组通字,【2021】8号);包头医学院博士科研基金项目(编号:BSJJ201809);内蒙古自治区2020年硕士研究生科研创新资助项目(编号:SZ2020056)。

摘　　要：目的:探究蒙古扁桃油对肺纤维化大鼠的影响。方法:将60只SPF级雄性SD大鼠按体重随机分为6组:正常对照组、模型对照组、醋酸泼尼松0.0015 g/kg组、蒙古扁桃油5、10、15 g/kg组。除正常对照组外,其他各组通过气管内滴注博莱霉素5 mg/kg建立肺纤维化模型,各组连续灌胃相应药物或生理盐水28 d后摘取肺组织用于苏木素-伊红(HE)、马森(Masson)等组织病理学分析及检测肺脏器指数、肺组织白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、Ⅲ型胶原(COL-Ⅲ)、Ⅳ型胶原(COL-Ⅳ)、透明质酸(HA)、层粘连蛋白(LN)、羟脯氨酸(HYP)等肺纤维化相关生化指标及转化生成因子β1(Tgf-β1)、Smad3及Smad7 mRNA表达。结果:与正常对照组比较,模型对照组大鼠HE及Masson病理组织学分析显示模型对照组炎症细胞明显浸润,间质水肿,肺泡结构丧失和纤维化病变,肺组织显示出严重的胶原沉积和纤维化病变,肺脏器指数、肺组织IL-6、IL-1β、COL-Ⅲ、COL-Ⅳ、HA、LN及HYP含量显著升高(P<0.01),肺组织Tgf-β1、Smad3 mRNA表达水平显著上调,Smad7 mRNA表达水平显著下调(P<0.01);与模型对照组比较,蒙古扁桃油5、10、15 g/kg组肺炎症较轻,可明显降低肺脏器指数(P<0.05或P<0.01),降低组织COL-Ⅳ、LN、IL-6、IL-1β、HYP及HA含量,以10 g/kg组降低最明显(P<0.05或P<0.01)。蒙古扁桃油10 g/kg能够明显改善胶原沉积和纤维化,明显下调大鼠组织中Tgf-β1、Smad3 mRNA(P<0.05或P<0.01)表达水平,促进Smad7 mRNA表达(P<0.05)。结论:蒙古扁桃油可有效减轻肺纤维化大鼠细胞外基质沉积,抑制胶原纤维增生,缓解肺部炎症及肺纤维化,可能通过调节TGF-β1/Smad信号通路对肺纤维化大鼠起到保护作用。Objective:To explore the effects of Amygdalus mongolica oil(AMO) against pulmonary fibrosis in rats.Methods:Sixty SPF male SD rats were randomly divided into the following six groups according to their body weight: a normal group, a model group, a prednisone acetate group(0.001 5 g/kg), and high-(15.0 g/kg), medium-(10.0 g/kg), and low-dose(5.0 g/kg) AMO groups.Pulmonary fibrosis model in rats was induced by intratracheal infusion of bleomycin(5 mg/kg) in all groups except for the normal group. After 28 days of intragastric administration, lung tissues were harvested for histopathological analysis after hematoxylin-eosin(HE) staining and Masson staining, followed by the detection of the organ index and biochemical indicators related to pulmonary fibrosis [such as interleukin-6(IL-6), IL-1β,type Ⅲ collagen(COL-Ⅲ), COL-Ⅳ,hyaluronic acid(HA),laminin(LN),and hydroxyproline(HYP)] and pathway proteins [such as transforming growth factor β1(TGF-β1),mothers against decapentaplegic homolog 3(Smad3),and Smad7].Results:As revealed by the histopathological analysis, the model group showed obvious infiltration of inflammatory cells, interstitial edema, loss of alveolar structure, fibrotic lesions, and serious collagen deposition and fibrosis in lung tissues compared with the normal group.Additionally, the model group displayed increased lung organ index, and IL-6,IL-1β,COL-Ⅲ,COL-Ⅳ,HA,LN, and HYP levels(P<0.01), up-regulated TGF-β1 andSmad3 mRNA levels, and down-regulated Smad7 mRNA level(P<0.01). Compared with the model group, the AMO groups, especially the medium-dose AMO group, relieved pneumonia, decreased lung organ index(P<0.05 or P<0.01), and dwindled COL-IV,LN,IL-6,IL-1β,HYP, and HA levels(P<0.05 or P<0.01). AMO at the medium dose improved collagen deposition and fibrosis, down-regulated TGF-β1 and Smad3 mRNA expression(P<0.05 or P<0.01), and stimulated the mRNA expression of Smad7(P<0.05). Conclusion:AMO effectively reduces the extracellular matrix deposition in pulmonary fibrosis rats, inhibits the p

关 键 词：蒙古扁桃油 博莱霉素 肺纤维化 转化生成因子β1/Smad3信号通路 肺脏保护 

分 类 号：R285.5[医药卫生—中药学]