核因子-κB在高脂饮食诱导的大鼠胰腺损伤中的作用

Role of nuclear factor kappa B in high fat diet induced pancreatic injuries in rats.

目的研究长期高脂饮食诱导的大鼠胰腺损伤及核因子-κB（NF-κB）在其发病机制中的作用。方法雄性Wistar大鼠14只分为高脂组和正常对照组,分别给予正常饮食和高脂饮食喂养20周。检测血清三酰甘油、总胆固醇及淀粉酶、脂肪酶、葡萄糖水平;常规HE染色观察胰腺病理改变;透射电镜观察胰腺超微结构改变;苦味酸-天狼猩红染色观察胶原形成;免疫组织化学染色检测NF-κB/p65、细胞间黏附分子-1（ICAM-1）和α-平滑肌动蛋白（α-SMA）表达;RT-PCR法检测胰腺组织中NF-κB/p65、ICAM-1、TNF-α、α-SMAmRNA水平。结果高脂组大鼠喂养2周后即出现高脂血症,20周末,高脂组大鼠血清三酰甘油和总胆固醇均高于对照组（P〈0.01）。20周后高脂组大鼠胰腺组织腺泡细胞萎缩、空泡变性;内质网明显扩张,血管内皮细胞间隙增宽,血管内皮断续;胰腺组织内有胶原形成。高脂组大鼠胰腺NF-κB/p65、ICAM-1和α-SMA蛋白高表达;高脂组大鼠NF-κB/p65、ICAM-1、TNF-α、α-SMAmRNA水平均较对照组明显增高（P〈0.05或P〈0.01）。结论长期高脂饮食可引起高脂血症和胰腺组织损伤,其分子机制与NF-κB活化及其下游分子的表达增强有关。

Objective To investigate the high-fat diet induced pancreatic injuries in rats. role of nuclear factor kappa B （NF-κB） in long-term Methods Fourteen male Wistar rats were divided into two groups and were fed for 20 weeks. Rats in control group were fed with normal diets while rats in another group were fed with high fat diets. Serum triacylglycerol, total cholesterol, glucose and pancreatic amylase and lipase were detected by an autoanalyzer. At the end of week 20, pancreatic tissues were obtained from all rats. Histopathological alterations were observed by H＆E staining and transmission electron microscopy; and collagen formation was observed by Sirius red staining under polarizing microscope. The expressions of NF-κB/p65, intercellular adhesion molecule 1 （ICAM-1） and α-smooth muscle actin（α-SMA） in pancreatic tissues were detected by immunohistochemical staining. NF-κB/p65, ICAM-1, TNF-α and α-SMA mRNA levels were determined by RT-PCR. Results Hyperlipidemia was detected in rats from high fat diet group at the end of week 2. After 20 weeks, vacuolization in acinar and islet cells, dilated rough endoplasmic reticulum and modified vascular endothelial cells were observed under light microscope and transmission electron microscope. In addition, NF-κB/p65, ICAM-1 and α-SMA were expressed strongly in pancreatic tissues of rats from high fat diet group. In rats fed with high fat diets, NF-κB/p65, ICAM-1, TNF-α and α-SMA mRNA levels were all elevated significantly in comparison with normal rats （P 〈 0.05 or P 〈 0.01, respectively）. Conclusions Long term high fat diet can induce hyperlipidemia and chronic pancreatic injuries, and NF-κB activation and its downstream molecules＇ over expression may play an important role in the underlying pathogenesis.