GPIHBP1基因敲除小鼠在严重高三酰甘油血症急性胰腺炎导致肺损伤研究中的应用

Application of GPIHBP 1 gene knockout mice in the study of lung injury induced by acute pancreatitis with severe hypertriglyceridemia

目的旨在通过基因修饰的高三酰甘油血症小鼠建立急性胰腺炎模型,观察胰腺与肺病理改变。方法采用野生小鼠与糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1,GPIHBP1)基因敲除小鼠,腹腔注射雨蛙素,诱导急性胰腺炎,检测血浆脂质与不同时间下淀粉酶活性,观察胰腺与肺组织病理形态改变。结果GPIHBP1基因敲除小鼠的血浆三酰甘油极度升高,在诱导急性胰腺炎后,淀粉酶活性明显改变,胰腺病理损伤加重,同时伴有肺损伤病变,肺泡灌洗液细胞数目明显增加。结论GPIHBP1基因敲除小鼠诱导急性胰腺炎后,胰腺与肺病理损伤明显加重,对进一步探讨高脂血症急性胰腺炎导致肺损伤及远隔器官损伤的发病机制具有一定的意义。

Objective To establish a model of acute pancreatitis in genetically modified mice with hypertriglyceridemia and to observe pathological changes of pancreas and lung tissues.Methods Wild type and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1(GPIHBP1)gene knockout mice with hypertriglyceridemia were used to induce acute pancreatitis via intraperitoneal injection of caerulein.Amylase activity and plasma levels of lipids were detected.Pathological changes of pancreas and lung tissues were observed.Results GPIHBP1 knockout mice showed extremely high plasma levels of triglycerides.Amylase activity was significantly altered after induction of acute pancreatitis.The pathological injury of pancreas was aggravated,accompanied by lung injury,and the cell number of alveolar lavage fluid significantly increased.Conclusion After induction of acute pancreatitis,the pathological damage of pancreas and lung tissues in GPIHBP1 knockout mice was significantly aggravated,indicating that it has certain significance for further exploring the pathogenesis of hyperlipidemic acute pancreatitis leading to lung and remote organ injury.