青蒿琥酯对2型糖尿病大鼠肺组织纤维化的防治作用  

Preventive and Therapeutic Effects of Artesunate on Pulmonary Fibrosis in Type Ⅱ Diabetic Rats

作　　者：时荣康 张思琴 李佳芮 赵丹妮 姚兆丰 王玉琛 徐嘉智 农晓琳[1] SHI Rongkang;ZHANG Siqin;LI Jiarui;ZHAO Danni;YAO Zhaofeng;WANG Yuchen;XU Jiazhi;NONG Xiaolin(College&Hospital of Stomatology,Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西医科大学口腔医学院/附属口腔医院,广西南宁530021

出　　处：《中华中医药学刊》2022年第11期81-86,I0031,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81860726)。

摘　　要：目的 观察青蒿琥酯(artesunate, ART)对糖尿病(diabetes mellitus, DM)大鼠肺脏的保护作用,并探讨其对肺组织纤维化的影响。方法 将60只大鼠随机分为5组,正常对照组(CON组),单纯糖尿病组(DM组),ART干预组(ART组),二甲双胍干预组(MET组)及联合用药干预组(COM组)。采用高糖高脂饲料喂养以及一次性腹腔注射链脲佐菌素(streptozocin, STZ)进行2型糖尿病(type 2 diabetes mellitus, T2DM)大鼠造模并行成模鉴定。在模型建立完成并稳定后用药干预4周,处死大鼠后取材。行苏木精-伊红染色(hematoxylin-eosin staning, HE)观察肺组织病理改变;行马松(Masson)与天狼星红染色(picrosirius red staining, PSR)观察肺组织纤维化改变;免疫组织化学染色法检测肺组织转化生长因子β1(transforming growth factor-β1,TGF-β1)、基质金属蛋白酶9(matrix metallopeptidase-9,MMP9)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)蛋白表达;实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction, qRT-PCR)检测肺组织TGF-β1、MMP9 mRNA表达情况。结果 HE染色显示DM组肺部组织结构紊乱,肺泡间隔增厚,出现肺实变;各用药干预组肺实变减轻,肺泡形态结构有所恢复。Masson与PSR染色显示DM组较CON组肺组织纤维化明显增多(P<0.05),各用药干预组较DM组肺组织纤维化均有所改善(P<0.05)。免疫组化染色法发现DM组较CON组肺脏组织中TGF-β1、MMP9、TNF-α、IL-1β蛋白表达显著提高(P<0.01),各用药干预组较DM组肺脏组织中各蛋白表达显著下降(P<0.05)。qRT-PCR结果显示DM组较CON组肺脏组织中TGF-β1、MMP9 mRNA表达显著升高(P<0.01),各用药干预组较DM组肺脏组织中TGF-β1、MMP9 mRNA表达均明显降低(P<0.05)。结论 结果表明ART对T2DM大鼠肺部纤维化具有防治作用,该作用与抑制TGF-β1、MMP9、TNF-α、IL-1β因子的表达有关。Objective This experiment observes the protective effect of Artesunate(ART)on the lungs of diabetes mellitus(DM)rats and explores its effect on lung fibrosis.Methods Sixty rats were randomly divided into 5 groups:normal control group(CON group),simple diabetes group(DM group),ART intervention group(ART group),metformin intervention group(MET group)and combination intervention group(COM group).The rats were fed with high-sugar and high-fat feed and a one-time intraperitoneal injection of streptozotocin(STZ)for modeling type 2 diabetes mellitus(T2 DM)rats.T2 DM models were made and model identification was performed.After the model was established and stabilized,the drug was used for 4 weeks.The rats were sacrificed and lung tissue samples were taken out.Hematoxylin-eosin staining(HE)was performed to observe the pathological changes of lung tissue.Masson and picrosirius red staining(PSR)were performed to observe the changes of lung tissue fibrosis.Immunohistochemical staining was processed to detect the expressions of transforming growth factor-β1(TGF-β1),matrix metallopeptidase-9(MMP9),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in lung tissue.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expressions of transforming growth factor-β1(TGF-β1)and matrix metalloprotein9(MMP9)mRNA in lung tissue.Results HE showed that the lung tissue structure of the DM group was disordered,the alveolar compartment was thickened and the lung consolidation appeared.In each medication intervention group,lung consolidation was reduced and alveolar structure had recovered.Masson and PRS staining showed that the DM group had significantly more lung fibrosis than the CON group(P<0.01).Compared with those of the DM group,the pulmonary tissue fibrosis of each medication intervention group was reduced(P<0.05).Immunohistochemical staining found that the expressions of TGF-β1,MMP9,TNF-αand IL-1βin the lung tissues of the DM group was significantly higher than that of the CON group(P<0.01).Co

关 键 词：2型糖尿病 青蒿琥酯 肺组织纤维化 TGF-Β1 炎症 大鼠 

分 类 号：R282.71[医药卫生—中药学]