DAR疗法对ANP大鼠门静脉血内毒素含量和胰腺组织核因子-κB表达的影响

Effect of DAR therapy on endotoxin and activation of NF-κB in rat model of ANP

目的研究DAR疗法治疗急性坏死性胰腺炎(ANP)的机制。方法实验动物为40只SD大鼠,用5%牛黄胆酸钠逆行胰胆管注射法制备ANP模型,造模成功后,随机分为DAR组和对照组,每组20只大鼠。DAR组用地塞米松(0.2mg/kg)、山莨菪碱(0.2mg/kg)腹腔注射,用生大黄(200mg/kg)灌胃;对照组用等量生理盐水替代地塞米松、山莨菪碱和大黄,用法同DAR组。两组大鼠均于6h后活杀,所有动物均取胰腺组织,用免疫组化法观察核因子-κB(NF-κB)的表达;每组随机选择10只动物,抽门静脉血,检测血清内毒素含量。结果DAR组门静脉血内毒素含量显著低于对照组(P=0.027),NF-κB表达强度明显弱于对照组(P=0.045),但两组NF-κB阳性细胞计数差异无统计学意义(P=0.862)。结论DAR疗法可能通过降低门静脉血内毒素含量、抑制NF-κB的表达强度来减轻ANP时的炎症反应,但又能避免过分抑制ANP时的炎症反应而造成的不良反应,从而可能起到预防多器官功能障碍综合征,降低ANP病死率的作用。这可能是DAR疗法治疗ANP的部分机制。

Objective To study the mechanism of action of DAR therapy on acute necrotizing pancreatits（ANP）. Methods 40 SD rats were randomly divided into DAR group and control group. Each group had 20 SD rats. 5% taurocholate was employed to develop ANP model. In DAR group dexamethasone （0. 2 mg/kg） and anisodamine （0. 2 mg/kg）were injected into peritoneal cavity, rhubarb （200 mg/kg） were lavaged. In control group, equal amont of normal saline were used the same way as used in DAR group. In 6 hs the animals were sacrificed and we harvested pancreatic tissue from 20 SD rats to assay activation of nuclear factor kappa -B （NF-κB） in each group. Portal vein blood samples were randomly collected with pyrogen free tubes from 10 SD rats for endotoxin measurement in each group. Results The content of portalvein venous plasma endotoxin in DAR group was significantly lower than that in control group （ P = 0. 027）. Strong activation of NF-κB in pancreas tissue in DAR group was significantly lower than that in control group （ P = 0. 045）. While the positive cells of NF -κB in two groups did not show significant difference （ P = 0. 862 ）. Conclusion DAR therapy might via decrease portal blood endotoxin, might through inhibit the activation of NF-κB to inhibit cascade inflammation in ANP, but not overwhelm inflammatory response in ANP. Thus DAR therapy might protect ANP from multiple organ dysfunction syndrome, and then decrease the mortality. These might be part of the treatment mechanisms of DAR therapy on ANP.