地塞米松对急性胰腺炎中TGF-β_(1)/Smad/ERK信号通路的影响  

Effect of dexamethasone on the TGF-β_(1)/Smad/ERK signaling pathway in acute pancreatitis

作　　者：马彦娟[1] 牛丽丹[1] 张建新[1] 吴畏[1] 孔令宇[1] 蔡君艳 石金河[1] MA Yanjuan;NIU Lidan;ZHANG Jianxin;WU Wei;KONG Lingyu;CAI Junyan;SHI Jinhe(Department of Emergency,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,China)

机构地区：[1]新乡医学院第一附属医院急诊科,卫辉453100

出　　处：《西北药学杂志》2021年第3期395-399,共5页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金青年基金项目(编号:81600677)。

摘　　要：目的探讨地塞米松(DEX)对急性胰腺炎(AP)胰腺组织中转化生长因子β_(1)(TGF-β_(1))/Smad/细胞外信号调节蛋白激酶(ERK)信号通路及miRNA-216a的影响。方法利用蛙皮素建立小鼠AP模型,实验分组为对照组、AP组和DEX组。检测3组小鼠血清中淀粉酶(AMY)与脂肪酶(LPS)的水平,利用RT-qPCR法检测胰腺组织中miRNA-216a mRNA的表达情况,利用Elisa法检测胰腺组织及血清中TGF-β_(1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL^(-1)β)的水平。利用Western Blot法检测各组胰腺组织中TGF-β_(1)、P-Smad3、Smad7与磷酸化细胞外信号调节蛋白激酶1/细胞外信号调节蛋白激酶2(P-ERK1/ERK2)的蛋白表达情况。结果与对照组比较,AP组血清中AMY与LPS的水平显著升高,与AP组相比,DEX组血清中二者的水平均显著降低;酶联免疫吸附(Elisa)结果显示,与AP组相比,DEX组胰腺组织及血清中IL^(-1)β、TNF-α、TGF-β_(1)与IL-6的水平均显著降低;RT-qPCR结果显示,与对照组比较,AP组胰腺组织中miRNA-216a mRNA的表达显著升高,而与AP组比较,DEX组胰腺组织中miRNA-216a mRNA的表达显著降低;Western Blot结果显示,与对照组比较,AP组胰腺组织中TGF-β_(1)、P-Smad3及P-ERK1/ERK2的蛋白表达显著升高,而Smad7的蛋白表达显著降低,与AP组比较,DEX组胰腺组织中TGF-β_(1)、P-Smad3及P-ERK1/ERK2的蛋白表达显著降低,而Smad7的蛋白表达显著升高。结论DEX一方面可抑制TGF-β_(1)的表达,进而促进Smad7的表达,抑制Smad3和ERK1/ERK2蛋白磷酸化,从而抑制TGF-β_(1)/Smad/ERK信号通路的激活;另一方面可抑制miRNA-216a的表达,最终减少炎症因子的合成与释放,对胰腺腺泡细胞具有保护作用。Objective To investigate the effect of dexamethasone(DEX)on the transforming growth factorβ_(1)(TGF-β_(1))/small mothers against decapentaplegic(Smad)/extra cellular signal regulated protein kinase(ERK)signaling pathway and miRNA-216a in pancreas in acute pancreatitis(AP).Methods The mouse AP model was established by using caerulein.The experimental groups were the control group,AP group and DEX group.The levels of amylase(AMY)and lipase(LPS)in serum were detected by using automatic biochemical analyzer.The expression of miRNA-216a mRNA in pancreas was detected by RT-qPCR.The levels of interleukin 1β(IL^(-1)β),tumor necrosis factor-α(TNF-α),TGF-β_(1) and interleukin 6(IL-6)in pancreas tissue and serum was detected by using Elisa method.The expression of miRNA-216a mRNA in pancreas was detected by quantitative real time-polymerase chain reaction(RT-qPCR)and the expression of TGF-β_(1),phosphorylation small mothers against decapentaplegic 3(P-Smad3),small mothers against decapentaplegic 7(Smad7)and phosphorylationextra cellular signal regulated protein kinase 1/extra cellular signal regulated protein kinase 2(P-ERK1/ERK2)protein in pancreas was detected by Western Blot.Results Compared with control group,the levels of AMY and LPS in AP group were significantly higher.Compared with AP group,the levels of AMY and LPS in DEX group were significantly lower.The results of Elisa test showed that the levels of IL^(-1)β,TNF-α,TGF-β_(1)and IL-6 in pancreas tissue and serum significantly reduced in DEX group,compared with the AP group.The RT-qPCR results showed the expression of miRNA-216a mRNA in pancreatic tissue of AP group was significantly higher than that of control group.The miRNA-216a mRNA in pancreatic tissue of DEX group was significantly lower than that of AP group.The results of Western Blot showed that the expression of TGF-β_(1),P-Smad3 and P-ERK1/ERK2 protein significantly increased and Smad7 protein significantly decreased in AP group,compared with control group.The expression of TGF-β_(1),P-Smad

关 键 词：急性胰腺炎(AP) 地塞米松(DEX) 转化生长因子β_(1)(TGF-β_(1))信号通路 miRNA-216a 

分 类 号：R965[医药卫生—药理学]