磷脂酶A2抑制剂对急性胰腺炎肠黏膜损伤的保护研究

目的探讨应用磷脂酶A2（PLA2）抑制剂对大鼠重症急性胰腺炎（SAP）埘肠黏膜损伤的保护作用及其机制。方法雄性Wistar大鼠36只，随机分为3组（n=12）：假手术组（SO组）、SAP组、PLA2抑制剂治疗组（抑制剂组）。胰胆管逆行注射5％牛磺胆酸钠诱导SAP模型，治疗组在造模后30rain腹腔注射PLA2抑制剂s5920／LY315920Na（0．5mg／100g）。各组于术后12h点处死大鼠，观察胰腺和肠黏膜组织病理学变化，检测血清淀粉酶（AMY）、血清和肠黏膜组织中sPLa22活性的变化，RT-PCR法检测肠黏膜组织sPLA2 mRNA表达。结果SAP组胰腺和肠黏膜组织病理改变明显，血清AMY水平、IL-1β含量、血清和肠组织sPLA2活性、sPLA2 mRNA表达水平均明显高于SO组（P〈0．05）。PLA2抑制剂治疗组胰腺和肠黏膜组织病理损害程度较轻，上述指标均明显低于SAP组（P〈0．05），但仍高于SO组（P〈0．05）。结论PLA2抑制剂可通过降低血清IL-1B、抑制sPLA2mRNA表达和下调血清及肠组织PLA2的活性等减轻SAP大鼠肠黏膜损伤。

Experimental Study on Therapeutic Effect of PhospholipaseA2 Inhibitor in Intestinal Mucosal Injury of Severe Acute Pancreatitis Rats

Objective To investigate the protective effects of phospholipase A2 inhibitor on severe acute pancreatitis（SAP）-associated intestinal mucosal injury in rats and its mechanism. Methods Thiry-six male Wistar rats were randomly divided into sham operation group （SO group）, SAP group and phospholipase A2 inhibitor treatment group （inhibitor group）. SAP model was induced by retrograde infusion of 5% sodium taurocholate into the biliopancreatie duct, and the inhibitor group was injected intraperitoneally with phospholipid A2 inhibitor S5920/LY315920Na（0.5mg/100g） 30min afte SAP model. Rats in all groups were executed at 12h after induction, the pathological changes of pancreas and intestinal mucosa were observed, and serum amylase, IL-113 contents and sPLA2 activity as well as sPLA2 activity in intestinal tissue were determined. The expression of sPLA2 mRNA in intestinal tissue was measured. Results In SAP group, the pathological changes of pancreas and intestinal mucosa were obvious, amylase, IL-1β contents in serum, sPLA2 activity in serum and intestinal tissue, and the expression of sPLA2 mRNA were significantly higher than those in SO group. The corresponding values in inhibitor group were lower than SAP group（P 〈0.01 ）, but were higher than SO group （P 〈0.01 ）. Conclusion Phospholipase A2 inhibitor has protective effect on intestinal mucosal injury in SAP rats through down-regulating the expression of sPLA2 mRNA and decreasing IL-1β level and sPLA2 activity in serum and intestinal tissue.