银杏苦内酯B对重症急性胰腺炎大鼠血浆细胞因子的影响

Effect of Ginkgolide B on plasma levels of cytokines in severe acute pancreatitis in rats

目的:观察重症急性胰腺炎(SAP)大鼠血浆中TNF-α,血小板活化因子(PAF),IL-10, IL-12,sTNFR的水平变化及其银杏苦内酯B(BN52021)的影响.方法:实验选用Wistar♂大鼠45只,随机分成SAP模型组(SAP,n=15),BN52021治疗组(BN,n=15)和阴性对照组(NC,n=15)．前两组以50 g／L牛磺胆酸钠逆行注入主胰管制成SAP模型,NC组开腹后仅翻动十二指肠并触摸胰腺数次关腹．制模15 min后,SAP组经股静脉以5 mL／mg注射生理盐水;BN组以BN52021(5 mg／kg)代替生理盐水静注．制模后分别于1,6,12 h采血,应用ELISA技术测定血浆TNF-α,PAF,IL-10,IL-12和sTNFR水平．结果:SAP组,NC组和BN组大鼠血浆TNF-α和PAF水平相比,具有显著性差异,SAP组(746．2±374．1,82．5±35．4 ng／L)显著高于NC组(385．1±86．3．1．1±1．9 ng／L),BN组(503．7±177．9,39．9±29．9 ng／L)显著低于SAP组(P<0．05)．血浆sTNFR水平三组相比存在明显差异,SAP组(488．7±363．8 ng／L)显著高于NC组(50．0±21．0 ng／L),BN组(883．4±552．5 ng／L)显著高于SAP组(488．7±363．8 ng／L)(P<0．05)．血浆IL-12三组相比存在明显差异,SAP组(97．1±55．9 ng／L)显著高于NC组(20．4±19．4 ng／L),BN组在1 h时相点(133．5±33．4 ng／L)显著高于SAP组(55．9±14．7 ng／L)(P<0．05)．血浆IL-10三组相比不存在明显差异(P>0．05)．结论:SAP大鼠促炎细胞因子和抗炎细胞因子均显著升高．BN52021能降低血浆促炎因子含量,提高IL-12和细胞因子拮抗剂sTNFR含量．

AIM： To observe the level changes of tumor necrosis factor-alpha （TNF-α）, platelet activating factor （PAF）, interleukin-10 （IL-10）, interleukin-12 （IL-12） and soluble TNF receptors （sTNFR） in rats with severe acute pancreatitis （SAP） and the influences of Ginkgolide B （BN52021） on the changes.METHODS： Male Wistar rats were randomly divided into 3 groups： SAP model group （SAP, n = 15）, BN52021 treatment group （BN, n = 15） and negative control group （NC, n = 15）. SAP was induced by retrograde infusion of 50 g/L sodium taurocholate into the pancreatic duct of rats. Sham operation was performed in the rats of NC group, while the rats in SAP and NC groups received the femoral vein injection of normal saline （5 mL/kg） 15 min after induction of SAP. Moreover, the rats in BN group received BN52021 injection instead of normal saline. After operation, the animals were sacrificed at 1^st, 6^th and 12^th h for plasma cytokines detection with enzyme-linked immunosorbent assay （ELISA）.RESULTS： The levels of plasma TNF-α and PAF were significantly higher in SAP group than those in NC group （746.2 ± 374.1 ng/L vs 385.1 ± 86.3 ng/L, P〈0.05; 82.5 ± 35.4 ng/L vs 1.1 ± 1.9 ng/L, P〈0.05）, but they were significantly decreased in BN group （503.7 ± 177.9, 39.9 ± 29.9 ng/L）（both P〈0.05）. The levels of plasma sTNFR were 50.0 ± 21.0, 488.7 ± 363.8, and 883.4 ± 552.5 ng/L in NC, SAP and BN group, respectively, and there were significant differences among them （P〈0.05）. Plasma IL-12 level was markedly increased in SAP group as compared with that in NC group （97.1 ± 55.9 ng/L vs 20.4 ± 19.4 ng/L, P〈0.05）, while it was further increased at the Ist h in BN group as compared with that in SAP group （133.5 ± 33.4 ng/L vs 55.9 ± 14.7 ng/L, P〈0.05）. The level of IL-10 was not significant different among the three groups （P 〉 0.05）.CONCLUSION： The plasma levels of pro- and anti-cytokines are increased in SAP rats, and BN52021 can inhibit the production of pro- cytokines and promote the secretion of anti- cytokines such as IL-12 and sTNFR to some extent.