血管生成素及其他炎症介质在大鼠急性胆源性胰腺炎中的变化规律及意义

Changes and significance of angiogenin and other inflammatory mediators in rats with acute biliary pancreatitis

目的:探讨血管生成素及其他炎症介质在急性胆源性胰腺炎中的变化及其意义。方法:将70只SD大鼠随机分成急性胆源性胰腺炎组(ABP组,胆总管末端结扎,n=56)和假手术组(SO组,仅行开腹后翻转胰腺,n=14),分为7个时间点(术后0、6、12、24、48、72、120 h)。各组处理后于相应时间点留取大鼠的胰腺和静脉血,测得胰腺含水量,观察ABP组及SO组胰腺病理变化及评分并检测血中淀粉酶(AMY)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、血管生成素-1(Ang-1)、血管生成素-2(Ang-2)的变化。结果:ABP组胆总管末端结扎术后各时间点的AMY、IL-10、TNF-α、NF-κB均高于同时间点的SO组(P<0.05),并于120 h达到观察期内峰值。Ang-1术后0 h即较SO组显著降低(P<0.01),后升高并于12 h后保持平稳,但始终低于SO组(P<0.05),与胰腺病理评分无相关性;Ang-2术后0 h即较SO组显著升高(P<0.01),并于48 h到达峰值,且与胰腺病理评分呈正相关(r=0.943,P<0.01),后缓慢下降但显著高于SO组,并失去与胰腺病理评分的正相关性。ABP组0~12 h,Ang-2与胰腺含水量呈正相关(r=0.830,P<0.01),24 h后无明显相关性。ABP早期,胰腺含水量急剧升高与Ang-1的下降及Ang-2的升高相对应。结论:炎症介质在ABP的发生发展中起到重要作用,而Ang-1水平与ABP严重程度无明显相关性,Ang-2水平在ABP早期上升,峰值提前于其他炎症介质,与胰腺病理评分及胰腺含水量呈正相关,Ang-2可能在ABP早期起到促炎及促血管渗漏的作用,预示胰腺炎的严重程度,或可用于指导临床治疗。

Objective：To study the function of angiogenin and other inflammatory mediators in rats with acute biliary pancreatitis （ABP）. Methods：Seventy SD rats were randomly divided into the ABP group （n=56, ligating bile pancreatic duct） and the SO （sham operation, only flipped pancreas） group （n=14）. The rats were sacrificed at 0, 6, 12, 24, 48, 72, and 120 hours after operation. The samples of blood serum and pancreas tissues were collected at each time point for detecting AMY, IL-10, TNF-α, NF- kB, Ang-1, Ang-2 levels using ELISA, pathological score and pancreatic moisture content. Results：The levels of AMY, IL-10, TNF-α, NF-kB at each time point in the ABP group were significantly higher than those in the SO group （P〈0.05）, and reached their peak value at 120 h during the observation period. The level of Ang-1 in the ABP group at 0 h decreased significantly（P〈0.01 ）, getting a little higher and remaining stable after 12 h. Ang-1 had no relationship with the severity of ABP. Ang-2 in the ABP group increased from 0 h, reaching its peak value at 48 h, and decreased at 72 h and 120 h. The level of Ang-2 in the ABP group was significantly higher than that in the SO group at each time point （P〈0.01）. Moreover, the level of Ang-2 was significantly positively correlated with ABP pathological score at the first 48 h （r=0.943, P〈0.01 ）, but the relationship was lost after 48 h. Similarly, the level of Ang-2 was also correlated with pancreatic moisture content during 12 h （r=0.830, P〈0.01）. Moreover, at first 6 h, pancreatic moisture content was significantly increased, which was corresponding to the decrease of Ang-1 and the increase of Ang-2. Conclusion：Inflammatory mediators play an important role in ABP. Ang-1 had no relationship with the severity of ABP. Elevated Ang-2 was significantly positively correlated with ABP pathological score and pancreatic moisture content in the early stage of ABP. Ang-2 may play a significant role in promoting vascular leak and proinflammatory effect in early stage of ABP, which indicates the severity of pancreatitis, or can be used to guide clinical treatment.