穿心莲内酯对大鼠腹腔粘连的抑制作用及其可能机制  

Inhibitory effect of andrographolide on abdominal adhesion in rats and its possible mechanism

作　　者：瞿慧 周继法 QU Hui;ZHOU Ji-fa(Department of Pharmacy,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanning 210029,China)【Abstract】ObjectiveTo investigate the inhibitory effect)

机构地区：[1]南京中医药大学附属医院药剂科,江苏省南京市210029

出　　处：《广西医学》2020年第6期715-720,768,共7页Guangxi Medical Journal

摘　　要：目的探讨穿心莲内酯(Ad)对大鼠腹腔粘连的抑制效果及其可能机制。方法(1)将60只SD雄性大鼠分为正常对照组、模型组、地塞米松组、Ad低剂量(20 mg/kg)组、Ad中剂量(40 mg/kg)组、Ad高剂量(80 mg/kg)组,各10只。除正常对照组外,其余各组大鼠均采用摩擦盲肠法制备腹腔粘连模型;建模后48 h,各药物组给予相应的药物干预10 d。给药结束后,评估各组大鼠腹腔粘连程度,并测定血清白细胞介素(IL)-1β、IL-18、肿瘤坏死因子α(TNF-α)水平,以及腹腔液中转化生长因子β(TGF-β)、结缔组织生长因子(CTGF)水平。(2)另收集50只雄性SD大鼠腹腔液,制备腹膜间皮细胞后分为照组、模型组、模型+不同浓度Ad组,各10只。模型组细胞加入TGF-β1培养,模型+不同浓度Ad组细胞加入TGF-β1和相应浓度的Ad(终浓度分别为10、20、40μmol/L)培养。培养24 h后检测各组细胞内Ⅰ型胶原(Col-Ⅰ)蛋白、Smad7、Smad2/3及磷酸化Smad2/3(p-Smad2/3)蛋白水平。结果(1)其他组粘连程度均重于正常对照组,地塞米松组与Ad中、高剂量组的粘连程度均轻于模型组(均P<0.05)。模型组血清IL-1β、IL-18与TNF-α水平均高于正常对照组(均P<0.05);各剂量Ad组血清IL-1β和TNF-α水平均较模型组降低;Ad中、高剂量组血清TNF-α水平均低于Ad低剂量组,Ad低剂量组、Ad中剂量组、Ad高剂量组血清IL-1β依次降低(均P<0.05)。模型组腹腔液TGF-β1和CTGF水平均高于正常对照组,Ad各剂量组的TGF-β1水平、Ad中、高剂量组的CTGF水平均低于模型组,Ad低剂量组、Ad中剂量组、Ad高剂量组的CTGF水平依次降低(均P<0.05)。(2)模型+不同浓度Ad组的Col-Ⅰ蛋白表达水平均低于模型组,且模型+10μmol/L Ad组、模型+40μmol/L Ad组、模型+20μmol/L Ad组的Col-Ⅰ蛋白表达水平依次降低(均P<0.05)。与模型组比较,模型+20μmol/L Ad组的p-Smad2/3与Smad2/3比值降低,模型+20μmol/L Ad组、模型+40μmol/L Ad组的Smad7蛋白表�Objective To investigate the inhibitory effect of andrographolide(Ad)on abdominal adhesion in rats and its possible mechanism.Methods(1)Sixty male SD rats were divided into normal control group,model group,dexamethasone group,low-dose Ad(20 mg/kg)group,moderate-dose Ad(40 mg/kg)group and high-dose Ad(80 mg/kg)group,with 10 rats in each group.Except the normal control group,abdominal adhesion model was established by rubbing caecum of the rats in the other groups;after 48 hours of modeling,all the drug groups were treated with corresponding medicine for 10 days.After drug withdraw,the degree of abdominal adhesion was assessed in the rats of all groups,besides,serum levels of interleukin(IL)-1β,IL-18 and tumor necrosis factorα(TNF-α),as well as the levels of transforming growth factorβ(TGF-β)and connective tissue growth factor(CTGF)in peritoneal fluid were detected.(2)Peritoneal fluid was collected from another 50 male SD rats,then the peritoneal mesothelial cells were prepared and divided into control group,model group,model+Ad with various concentration groups,with 10 rats in each group.Cells in the model group were cultured with TGF-β1,and cells in the model+Ad with various concentration groups were cultured with TGF-β1 and Ad with corresponding concentration(final concentration was 10,20 or 40μmol/L).After 24 hours of culture,the levels of collagen typeⅠ(Col-Ⅰ)protein,Smad7,Smad2/3 and phosphorylated Smad2/3(p-Smad2/3)proteins were measured in the cells of all groups.Results(1)The adhesion degree of the other groups was more severe than that of the normal control group,and the dexamethasone group and the moderate-and high-dose Ad groups obtained milder adhesion as compared with the model group(all P<0.05).The serum IL-1β,IL-18 and TNF-αlevels in the model group were higher than those in the normal control group(all P<0.05);each Ad group exhibited lower serum IL-1βand TNF-αlevels compared with the model group;the serum TNF-αlevel in the moderate-and high-dose Ad groups was lower than that in the

关 键 词：腹腔粘连 穿心莲内酯 炎症因子 结缔组织生长因子 转化生长因子Β SMAD信号通路 大鼠 大鼠腹膜间皮细胞 

分 类 号：R285[医药卫生—中药学] R619[医药卫生—中医学]