摘要
目的探讨急性胰腺炎（AP）大鼠P13K／Akt/mTOR信号通路与HIF-1α表达的关系。方法56只雄性SD大鼠随机分为7组：空白对照组（n=8）、假手术组（n=8）、AP模型组（n=8）、wortmannin预处理组（n=8）、rapamycin预处理组（n=8）、wortmannin＋rapamycin预处理组（n=8）和溶剂对照组（n=8）。用逆行胰胆管注射5％牛磺胆酸钠制备大鼠AP模型，wortmannin预处理组、rapamycin预处理组、wortmannin＋rapamycin预处理组分别于AP模型复制前30min腹腔注射wortmannin、rapamycin、wortmannin＋rapamycin DMSO／PBS溶液，溶剂对照组仅注射DMSO／PBS溶液。模型复制成功后6h处死大鼠取胰头部胰腺组织，应用Westernblot检测HIF-1α、Akt、P—Akt、p70^s6k、P—p70^s6k蛋白的表达。结果Akt、p70^s6k蛋白在胰腺组织中表达稳定，各组间差异无统计学意义（P〉0．05），HIF—1α、P—Akt、P—p70^s6k蛋白在空白对照组和假手术组中均有极少量阳性表达，两组间差异无统计学意义（P〉0．05）。AP模型组HIF-1α、P—Akt、P—p70^s6k蛋白含量与空白对照组相比明显升高（P〈0．01）；wortmannin预处理组、rapamycin预处理组、wortmannin＋rapamycin预处理组中HIF-1α、P—p70^s6k蛋白表达明显高于空白对照组（P〈0．01），但较AP模型组明显降低（P〈0．01），其中HIF-1α蛋白表达在wortmannin＋rapamycin预处理组比wortmannin预处理组、rapamycin预处理组降低更明显（P〈0．05）。HIF-1α、P—Akt、P—p70“蛋白含量在溶剂对照组和AP模型组之间差异无统计学意义（P〉0．05）。结论P13K／Akt／mTOR信号通路阻断剂wortmannin、rapamycin能够显著降低急性胰腺炎大鼠HIF-1α的表达，P13K／Akt／mTOR信号通路参与了HIF-1α的表达调控，P13K／Akt／mTOR信号通路可作为AP防治中的新靶点。
Objective To observe the relationship between PI3K/Akt/mTOR signal pathway and the expression of HIF - 1α in rats with acute pancreatitis. Methods Fifty - six male SI） rats were divided randomly into seven groups as normal control group（ n = 8 ）, sham operation group（ n = 8 ）, acute pancreatitis（ AP ） group （ n = 8 ）, wortmannin pretreatment group （ n = 8 ）, rapamiycin pretreatment group （n = 8 ） , wortmannin ＋ rapamycin pretreatment group （ n = 8 ） and the solvent of DMSO/PBS control group（n = 8 ）. The rats model with AP was made by injection with 5% sodium deoxycholate through retrogradely bilio pancreatic ducts. For the groups of wortmannin pretreatment, rapamiycin pretreatment, wortmannin ＋ rapamycin pretreatment were given intraperitoneal injection with the reagents of wortmannin, rapamiycin and wortmannin ＋ capamycin respectively prior to the AP model was made, the solvent control group only given the DMSO/PBS solution and only operation procedure for sham operation group. The pancreatic tissues were harvested at 6 hours after the model set up, the protein expression of HIF - 1α, Akt, p - Akt, p70^s6k, and p - p70^s6k were detected by western blot respectively in pancreatic tissues. Results The proteins expression of Akt, p - p70^s6k were stable, and there is no significant difference in groups （P 〉 0. 05 ）. There were seldom proteins expression of HIF - 1α, p - Akt, p- p70^s6k both in the normal control group and the sham operation control group, and there was no significant difference between these two groups （ P 〉 0. 05 ）. The proteins of HIF - 1 α, p - Akt, p - p70^s6k were significantly higher in the AP group than that in the normal control group （ P 〈 0.01 ）. The expression of HIF - 1 α, p -p70^s6k were significantly decreased in the pretreatment groups of wortmannin, rapamycin and wortmannin ＋ rapamycin compared to that in the AP group （ P 〈 0. 01 ）, among them HIF- 1α was more decreased in wortmannin ＋ rapamycin group than tha
出处
《中国急救医学》
CAS
CSCD
北大核心
2010年第4期330-334,共5页
Chinese Journal of Critical Care Medicine
