摘要
目的:考察莲心碱对佛波酯(TPA)所致耳肿胀炎症模型小鼠的抗炎作用,并探讨其作用机制。方法:将40只小鼠随机分为空白组、模型组、阳性对照组(地塞米松,2.5 mg/kg)和莲心碱低、高剂量组(5、15 mg/kg),每组8只。除空白组外,其余各组小鼠均于右耳内外侧涂抹TPA建立耳肿胀炎症模型;造模同时,各给药组小鼠均按20μL/只于右耳内外侧涂抹相应药液(以丙酮为溶剂),空白组和模型组小鼠涂抹等体积丙酮溶液。给药6 h后,测定小鼠耳厚度和耳肿胀度,苏木精-伊红染色后观察小鼠耳组织病理学变化,采用酶联免疫吸附法测定小鼠耳组织中炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β]水平,Western blot法测定小鼠耳组织中核转录因子κB信号通路相关蛋白[NF-κB p65和NF-κB抑制蛋白(IκBα)]的磷酸化水平,并采用实时荧光定量-聚合酶链式反应法检测小鼠耳组织中环氧化酶2(COX-2)、诱导型一氧化氮合成酶(iNOS)mRNA表达。结果:与空白组比较,模型组小鼠耳厚度、耳肿胀度和耳组织中炎症因子水平、NF-κB信号通路相关蛋白的磷酸化水平以及COX-2、iNOS mRNA表达水平均显著升高(P<0.05);耳组织发生增厚、炎性细胞浸润增多等变化。与模型组比较,各给药组小鼠耳厚度、耳肿胀度及耳组织中上述指标水平均显著降低(P<0.05),耳组织增厚和炎性细胞浸润等均得到显著减轻。结论:莲心碱对TPA所致耳肿胀炎症模型小鼠具有较好的抗炎作用,其机制可能与抑制耳组织中NF-κB p65、NF-κB蛋白的磷酸化,进而抑制炎症因子COX-2、iNOS mRNA表达有关。
OBJECTIVE:To investigate the anti-inflammatory effects of liensinine on 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced ear edema inflammatory model mice,and to investigate its mechanism.METHODS:The 40 mice were randomly divided into blank group,model group,positive control group(dexamethasone,2.5 mg/kg)and liensinine low-dose and high-dose groups(5,15 mg/kg),with 8 mice in each group.Except for blank group,other groups were given TPA for external use on both inner and outer sides of right ear to induce ear edema inflammatory model.During modeling,administration group was given relevant medicine 20μL/mice for external use on both inner and outer sides of right ear(using acetone as solvent);blank group and model group were given constant volume of acetone.6 h after administration,ear thickness and ear edema degree of mice were determined.The pathological changes of ear tissue were observed by HE staining.The levels of inflammatory factors(TNF-α,IL-6,IL-1β)in ear tissue were detected by ELISA.The phosphorylation levels of nuclear factorκB(NF-κB)signaling pathway related protein[NF-κB p65,NF-κB inhibitory protein(IκBα)]were detected by Western blot assay.mRNA expressions of COX-2 and iNOS were detected by RT-PCR.RESULTS:Compared with blank group,degree of ear edema,the levels of inflammatory factors in ear tissue,phosphorylation levels of NF-κB signaling pathway related protein,mRNA expressions of COX-2 and iNOS were increased significantly(P<0.05).There were ear tissue thickening and increase of inflammatory cell infiltration,etc.Compared with model group,ear edema degree and above indexes of ear tissue in administration group were decreased significantly(P<0.05);ear tissue thickening and increase of inflammatory cell infiltration were relieved significantly.CONCLUSIONS:Liensinine shows good anti-inflammatory effects on TPA-induced ear edema inflammatory model mice,the mechanism of which may be associated with inhibiting the phosphorylation levels of NF-κB p65 and NF-κB protein and inhibiting the mRNA
作者
姚茹
张锐虎
王璐
王晨阳
郭民
宋国华
陈朝阳
YAO Ru;ZHANG Ruihu;WANG Lu;WANG Chenyang;GUO Min;SONG Guohua;CHEN Zhaoyang(Laboratory Animal Center of Shanxi Medical University/Shanxi Key Lab of Experimental Animal Science and Animal Model of Human Disease,Taiyuan 030001,China)
出处
《中国药房》
CAS
北大核心
2018年第17期2364-2368,共5页
China Pharmacy
基金
山西省科技厅实验动物专项资金项目(No.2015K02)
