磷脂酶A_2在大鼠急性胰腺炎并发肺损伤中的作用及维拉帕米的治疗效应

Role of phospholipase A_2 in injury of lung complicated by acute pancreatitis and the therapeutic effect and mechanism of verapamil on it

目的 :观察磷脂酶 A2 (PL A2 )在大鼠急性胰腺炎 (AP)并发肺损伤中的作用及维拉帕米 (verapamil)的治疗效应 ,并对其治疗作用的机制进行探讨。方法 :取 82只 SD大鼠 ,雌雄不拘 ,随机数字表法分为模型组、维拉帕米组及假手术组 ;经胰胆管逆行注射质量分数为 3%的牛磺脱氧胆酸钠 (0 .1ml/10 0 g) ,制成 AP模型 ,并按分组情况分别给予药物或生理盐水 ;制模后 4 h、8h记录腹水量 ,测定血浆中钙离子浓度和淀粉酶活性及腹水和肺组织匀浆中 PL A2 活性的变化 ,计算肺系数 ,光镜下观察胰腺及肺组织的病理变化 ,记录动物的存活时间及 2 4 h死亡率。结果 :维拉帕米能有效减轻 AP大鼠胰腺及肺组织的病理性损伤 ,减少腹水生成 ;与模型组相比 ,维拉帕米组血浆钙离子浓度进行性下降的程度减轻 ,淀粉酶活性降低 ,腹水及肺匀浆中 PL A2 活性显著降低 ;维拉帕米可降低 AP大鼠的死亡率 ,延长动物的生存时间。结论 :PL A2 在 AP并发肺损伤的病理过程中发挥重要的作用 ,维拉帕米可以通过钙通道拮抗作用抑制 PL A2 的活性 ,减轻胰腺及肺的损伤而对 AP并发肺损伤发挥治疗作用。

Objective: To investigate the role of phospholipase A 2(PLA 2) in injury of lung complicated by acute pancreatitis(AP) and the therapeutic effect of verapamil, furthermore to explore its possible mechanism. Methods: Eightytwo SpragueDawley rats both male and female were divided into three groups. AP was induced by injecting 3% sodium deoxycholate (1 ml/kg) into the biliopancreatic duct except the rats of sham operation group. Ten minutes after operation, rats were injected intraperitoneally with saline or verapamil, respectively. At 4 hours and 8 hours after treatment, the volume of ascites and pulmonary coefficient were measured. The amylase activity and calcium concentration in plasma and PLA 2 in ascites and homogenate of lung were determined. The survival time and mortality of rats in different groups were recorded, and the pathomorphism of pancreas and lung was observed under microscope. Results: Verapamil reduced the mortality ( P <0 05), and prolonged the survival time of rats with AP significantly ( P <0 05), attenuated ascites volume, amylase activity and hypocalcemia in plasma, PLA 2 activity in ascites and lung homogenate, and ameliorated the inflammatory injury of pancreas and lung. Conclusion: The results suggest that PLA 2 plays a role in the injury of lung complicated by AP and verapamil possesses a therapeutic effect on the AP induced by sodium deoxycholate in rats, in which the mechanism might be due to inhibit PLA 2 activity by blocking calcium channel to ameliorate the damage of pancreas and lung which is induced by the overload of Ca 2+ .