熊果酸通过抑制TLR4/NF-κB通路以及Caspase-3蛋白的表达对慢阻塞疾病大鼠的影响  

Effects of ursolic acid on Caspase-3 protein expression in rats with chronic obstructive disease via TLR4/NF-κB pathway

作　　者：余晓丹[1] 李铮[1,2] YU Xiao⁃dan;LI Zheng(Department of Respiratory and Critical Care Medicine,The Fifth People's Hospital of Chengdu,Chengdu 611130,China)

机构地区：[1]成都市第五人民医院呼吸与危重症医学科,四川成都611130 [2]成都市第五人民医院神经内科,四川成都6111130

出　　处：《解剖学研究》2019年第6期483-486,共4页Anatomy Research

基　　金：四川省卫生计划生育委员会科研项目(17PJ046)

摘　　要：目的探究熊果酸(UA)通过Toll样受体//核转录因子κB(TLR4/NF-κB)通路对慢阻塞疾病(COPD大鼠Caspase-3蛋白表达的影响。方法 SD大鼠随机分为对照组、COPD组、COPD+UA组和COPD+EVP4593组。通过烟雾暴露+脂多糖建立COPD模型。比较各组大鼠肺功能、肺组织苏木精-伊红(HE)染色情况。检测和比较各组大鼠血清炎性因子和TLR4、NF-κB p65和Caspase-3蛋白表达水平。结果建模后COPD组大鼠的FEV0.3%/FVC和MMEF均显著低于对照组(P<0.01),的COPD+UA组和COPD+EVP4593组FEV0.3%/FVC和MMEF显著高于COPD组(P<0.01)。COPD组肺泡结构紊乱,肺泡间隙明显增厚,肺组织浸润大量炎症细胞,间质出血出现充血和出血改变。COPD组和COPD+EVP4593组的肺泡结构较正常,炎症浸润很少。COPD组的血清炎性因子显著升高(P<0.01),COPD+UA组和COPD+EVP4593组的TNF-α、IL-1β、IL-6水平显著低于COPD组(P<0.01)。COPD组的TLR4、NF-κB p65和Caspase-3蛋白水平显著升高,COPD+UA组和COPD+EVP4593组的TLR4、NF-κB p65和Caspase-3蛋白水平显著低于COPD组(P<0.01)。结论 UA可能通过抑制TLR4/NF-κB通路,减少炎性因子的表达和Caspase-3蛋白的水平,减少COPD大鼠肺损伤,保护肺功能。Objective To explore the effects of ursolic acid on Caspase-3 protein expression in rats with chronicobstructive disease via TLR4/NF-κB pathway.MethodsSD rats were randomly divided into control group,COPD group,COPD+UA group and COPD+EVP4593 group. A COPD model was constructed by exposure to smoke + lipopolysaccharide.The lung function and HE staining of lung tissue were compared between the groups. Serum inflammatory factors and TLR4,NF-κB p65 and Caspase-3 protein expression levels were detected and compared in each group.ResultsAfter modeling,the FEV0.3%/FVC and MMEF of the COPD group were significantly lower than the control group(P<0.01). The FEV0.3%/FVC and MMEF in the COPD+UA group and the COPD+EVP4593 group were significantly higher than those in the COPDgroup(P<0.01). In the COPD group,the alveolar structure was disordered,the alveolar space was thickened,and the lungtissue infiltrated a large number of inflammatory cells. Interstitial hemorrhage showed hyperemia and hemorrhage. Thealveolar structure of the COPD group and the COPD+EVP4593 group were normal and the inflammation infiltration was rare.The serum inflammatory factors in the COPD group were significantly increased(P<0.01). The levels of TNF-α,IL-1β andIL-6 in COPD+UA group and COPD+EVP4593 group were significantly lower than those in COPD group(P<0.01). Thelevels of TLR4,NF-κB p65 and Caspase-3 in the COPD group were significantly increased. The levels of TLR4,NF-κBp65 and Caspase-3 in COPD+UA group and COPD+EVP4593 group were significantly lower than those in COPD group(P<0.01).ConclusionUA could reduce lung injury and protect lung function by inhibiting TLR4/NF-κB pathway,reducinginflammatory factor expression and Caspase-3 protein levels in COPD rats.

关 键 词：慢性阻塞性肺病 熊果酸 TOLL样受体 核转录因子ΚB 半胱氨酸天冬氨酸蛋白酶-3 

分 类 号：R285.5[医药卫生—中药学]