自噬相关基因LC3和Beclin1在大鼠急性坏死性胰腺炎中的表达和意义

Signifi cance of expression of autophagy-related proteins LC3 and Beclin-1 in acute necrotizing pancreatitis in rats

目的:研究大鼠急性坏死性胰腺炎(ANP)胰腺组织LC3、Beclin1的表达,并探讨其在ANP中的作用及意义.方法:36只SD大鼠随机分为假手术(SO)组和ANP组,ANP组采用胰胆管逆行注射5%牛磺胆酸钠诱导制作大鼠ANP模型,SO组开腹后翻动胰腺后关腹,各组再分3、6和12h3个不同时间点.观察各组大鼠血清炎症因子及胰腺的病理改变,运用免疫组织化学法检测各组大鼠在不同时间点胰腺组织LC3和Beclin1的变化.结果:ANP组血浆淀粉酶(U/L)、TNF-α(μg/L)较SO组明显增加(血浆淀粉酶:3h:4936±1207vs1447±355;6h:5464±768vs1513±333;12h:6139±710vs1539±231;TNF-α:3h:111.24±21.86vs56.14±7.69;6h:107.55±33.05vs57.13±11.30;12h:108.24±24.83vs58.60±9.54,均P<0.05),且ANP组大鼠胰腺病理改变随着时间延长加重.正常大鼠胰腺腺泡细胞LC3、Beclin1低表达,大鼠ANP3h后胰腺细胞LC3、Beclin1表达开始增多,在6和12h呈强表达.结论:大鼠ANP后胰腺组织Beclin1和LC3增多,表明ANP后胰腺自噬活性增强,其表达与炎症变化程度相关,细胞自噬增强是可能对损伤的反应.

AIM： To examine the expression of microtubuleassociated protein 1 light chain 3 （LC3） and Be-clin-1 in acute necrotizing pancreatitis （ANP） in rats and to analyze their signif icance.METHODS： Thirty-six Sprague-Dawley rats were randomized into sham operation （SO） group and ANP group. ANP was induced in rats by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct. Rats were killed at 3, 6, and 12 h after sodium taurocholate injection. Pancreatic histopathological changesand serum levels of several inflammatory factors were measured. The expression of LC3 and Beclin-1 in ANP at different time points was detected by immunohistochemistry.RESULTS： Pancreatic pathological changes were gradually exacerbated with time in the ANP group. Serum levels of amylase （AMY, U/L） and TNF-α （μg/L） were significantly higher in the ANP group than in the SO group at all time points （AMY： 3 h： 4 936 ± 1 207 vs 1 447 ± 355; 6 h： 5 464 ± 768 vs 1 513 ± 333; 12 h： 6 139 ± 710 vs 1 539 ± 231; TNF-α： 3 h： 111.24 ± 21.86 vs 56.14 ± 7.69; 6 h： 107.55 ± 33.05 vs 57.13 ± 11.30; 12 h： 108.24 ± 24.83 vs 58.60 ± 9.54, all P 0.05）. The expression levels of LC3 and Beclin-1 in the pancreas were maintained at a very low level in the SO group, but started to elevate at 3 h in the ANP group and showed strong expression at 6 and 12 h （all P 0.05）.CONCLUSION： The expression levels of LC3 and Beclin-1 increased in ANP in rats, suggesting that up-regulation of autophagic activity may represent a response to injury in rats with ANP.