腹炎消通过调控Notch2/Hes-1通路对重症胰腺炎大鼠急性肺损伤的影响

Effects of Fuyanxiao on acute lung injury in rats with severe acute pancreatitis via Notch2/Hes-1 pathway

目的探究腹炎消对重症急性胰腺炎大鼠急性肺损伤的影响及可能的作用机制。方法SD大鼠随机选取12只作为假手术组,其余大鼠采用3.5%牛磺胆酸钠诱导建立重症急性胰腺炎模型。造模成功后将大鼠分为模型组,DAPT(Notch信号通路抑制剂)组,腹炎消低、高剂量组,腹炎消+DAPT组,每组12只,给药24 h。计算肺组织湿/干质量比,采用血气分析仪测定血氧分压(PaO_(2))和二氧化碳分压(PaCO_(2)),并计算氧合指数(PaO_(2)/FiO_(2)),比色法检测血清淀粉酶(AMY)活性,ELISA法检测肺匀浆液中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、细胞间粘附分子-1(ICAM-1)水平,HE染色观察胰腺、肺组织病理学变化,免疫组化法和RT-qPCR法检测肺组织Notch2、Hes-1蛋白和mRNA表达。结果与假手术组比较,模型组大鼠PaO_(2)、PaO_(2)/FiO_(2)降低(P<0.05),PaCO_(2),肺组织湿/干质量比,血清AMY活性,肺组织TNF-α、IL-6、ICAM-1水平及Notch2、Hes-1蛋白和mRNA表达升高(P<0.05),胰腺和肺组织水肿严重、炎性细胞浸润明显,有出血和坏死,肺泡间隔增厚;与模型组比较,DAPT组和腹炎消各剂量组以上指标均得到改善(P<0.05)。结论腹炎消可能通过抑制Notch2/Hes-1通路的激活,降低肺部炎症,改善与重症急性胰腺炎相关的急性肺损伤。

AIM To explore the effects of Fuyanxiao on acute lung injury in rats with severe acute pancreatitis,and to investigate its possible mechanism.METHODS SD rats,except twelve of them randomly assigned into the sham operation group,were induced into severe acute pancreatitis models by 3.5%sodium taurocholate,after which the rats were divided into model group,DAPT(Notch signal pathway inhibitor)group,groups for low dose and high dose Fuyanxiao use,and a group for intervention of DAPT and high dose Fuyanxiao,with 12 rats in each group,for 24 hours corresponding administration.The rats had their pulmonary wet/dry mass ratio calculated;their partial pressure of blood oxygen(PaO_(2))and carbon dioxide(PaCO_(2))measured by blood gas analyzer for the oxygenation index(PaO_(2)/FiO_(2))calculation;their activity of serum amylase(AMY)detected by colorimetry;their levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and intercellular detected by ELISA;their histopathological changes of pancreas and lung observed by HE staining;and their pulmonary expressions of Notch2,Hes-1 proteins and mRNA detected by immunohistochemistry and RT-qPCR.RESULTS Compared with the sham operation group,the model group displayed lower PaO_(2)and PaO_(2)/FiO_(2)(P<0.05),higher PaCO_(2),pulmonary wet/dry mass ratio,serum AMY activity,pulmonary levels of TNF-α,IL-6 and ICAM-1,and expressions of Notch2,Hes-1 proteins and mRNA(P<0.05),more severe edematous pancreas and lung tissues,more obvious inflammatory cell infiltration,bleeding and necrosis,and thickened alveolar septum as well.But the aforementioned indicators levels in the DAPT group and each Fuyanxiao group were improved significantly(P<0.05).CONCLUSION Fuyanxiao may reduce lung inflammation and improve acute lung injury in severe acute pancreatitis via inhibiting the activation of Notch2/Hes-1 pathway.