摘要
目的研究高脂血症所致大鼠急性胰腺炎早期基因表达变化。方法以高脂饮食(77%普通饲料+20%猪油+3%胆固醇)制备高脂血症SD大鼠模型,取正常和高脂大鼠各18只,铃蟾肽腹腔注射制备急性水肿型胰腺炎(AEP),两组其余各38只动物逆行胰胆管注射牛磺胆酸钠制备急性坏死型胰腺炎(ANP)。观察各组大鼠3、6、24 h胰腺组织病理学变化差异(每组6只),并比较1周时两组ANP大鼠的死亡率(每组20只)。采用高密度寡核苷酸芯片观察急性胰腺炎早期胰腺基因表达谱变化。结果1周时高脂ANP组死亡率明显高于单纯ANP组(75%比50%);参照Schmidt胰腺组织半定量积分法,高脂各组较相对应正常血脂组的胰腺坏死、出血、炎性细胞浸润程度均加重,尤以6 h组为最。6 h时,高脂AEP组与正常血脂AEP组相比,水肿、坏死、出血、炎性细胞浸润指数分别为:3.92±0.20比3.00±0.00、3.92±0.20比2.42±0.49、1.83±0.26比0.42±0.20、1.83±0.26比0.58±0.38,差异有统计学意义(P值均<0.05)。高脂ANP与正常血脂ANP组相比,坏死、出血、炎性细胞浸润指数分别为:4.00±0.00比3.25±0.29、3.42±0.80比1.80±1.09、2.67±1.03比1.13±0.25,差异有统计学意义(P值均<0.05);水肿指数为3.58±0.38比3.25±0.29,差异无统计学意义(P>0.05)。急性胰腺炎诱导3 h后,高脂组及正常血脂组胰腺表达均上调的基因有10个,表达均下调的基因有49个(其中11个为表达序列标签,EST)。结论高脂血症可增加大鼠ANP时的死亡率,加重大鼠AEP和ANP时胰腺病理变化;其机制可能为高脂血症影响信号转导,加重氧化应激、能量代谢紊乱等。
Objective To study the changes of pancreatic gene expression in Sprague-Dawley(SD) rats with acute pancreatitis induced by hyperlipidemia. Methods One hundred and twemy four SD rals were divided into two groups, half of which were fed a high-fat diet( 77 % normal diet+ 20 % animal fal + 3% cholesterol) for three weeks, the other half received normal diet. Acute edemalous pancrealitis (AEP) was induced by intraperitoneal injection of caerulein, while acute necrotizing pancreatilis(ANP) was induced by retrograde injections of taurocholate. Histology was compared at 3, 6 and 24 hours. The death rate was compared on the seventh day in ANP rats. Gene expression was evaluated by microarrays of full-length rat gene chips. Results Death rate, pancreatic injury scores were higher in hyperlipidemia groups than in normal diel groups. Ten up-regulated genes and 49 down-regulated genes including 1 t expressed sequence tags(ESTs) were found in both AEP and ANP models. They might limit or expand the severity of the disease in the condition of hyperlipidemia. Conclusions Hyperlipidemia can exacerbate pancreatic injury in acute pancreatitis in rats. The possible mechanism may lie in abnormal signal transduction, energy metabolic disorder and oxidative stress.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2007年第5期322-325,共4页
Chinese Journal of Digestion
关键词
胰腺炎
高脂血症
寡核苷酸序列分析
Pancreatitis
Hyperlipidemia
Oligonucleotide array sequence analysis