大黄对大鼠肠缺血再灌注所致肺损伤过程肿瘤坏死因子、一氧化氮和磷脂酶A_2的影响

Effect of rhubarb on tumor necrosis factor,nitric oxide and phospholipase A 2 in the development of lung injury after intestinal ischemiareperfusion in rats

目的：观察肿瘤坏死因子（ＴＮＦ）、内源性一氧化氮（ＮＯ）和磷脂酶Ａ２（ＰＬＡ２）在大鼠小肠缺血再灌注（ＩＲ）所致肺损伤发病过程中的作用，及大黄对ＴＮＦ、ＮＯ和ＰＬＡ２的影响，探讨大黄防治肠源性肺损伤的机制。方法：ＳＤ大鼠随机分为肠缺血再灌注组、假手术组、大黄治疗组和安慰剂组。以１２５Ｉ标记小牛血清白蛋白（ＢＳＡ）肺摄取指数作为评价肺损伤的指标，以髓过氧化物酶（ＭＰＯ）作为评价多形核白细胞（ＰＭＮ）在组织中聚集的指标，分别测定各组动物不同时间血浆、肺组织ＴＮＦ含量，血浆（血清）、肺及小肠组织内源性ＮＯ含量及ＰＬＡ２活性。结果：大黄可显著改善ＩＲ导致的低血压状态并明显抑制再灌注导致的肺ＭＰＯ活性升高（Ｐ＜０．０１）；抑制肠缺血和再灌注早期出现的血浆及肺组织ＴＮＦ水平升高（Ｐ＜０．０１）；抑制肠缺血期和再灌注期血清、肺及小肠组织ＰＬＡ２活性升高（Ｐ＜０．０５或Ｐ＜０．０１）及再灌注期的内源性ＮＯ释放（Ｐ＜０．０５或Ｐ＜０．０１）；降低肺毛细血管通透性（Ｐ＜０．０１）。结论：缺血再灌注早期应用大黄能明显防治大鼠ＩＲ所致的肺损伤，这种作用可能是通过抑制ＴＮＦ、内源性ＮＯ及ＰＬＡ２等介质的释放实现的。

Objective:To investigate the potential role of tumor necrosis factor(TNF),nitric oxide (NO) and phospholipase A 2 (PLA 2) in the development of lung injury,and the effect of rhubarb on TNF,NO and PLA 2 release after intestinal ischemiareperfusion (IIR).Methods:Adult SpragueDawley rats were subjected to intestinal ischemia (45 minutes of superior mesenteric artery occlusion alone) followed by 6 hours of reperfusion.Animals were divided into four groups:①ischemia and reperfusion alone ( n =24);②rhubarb treatment (600 mg/kg 30 minutes before reperfusion, n =24);③placebo controls (normal saline instead of rhubarb, n =16);④sham operated controls (laparotomy, n =16).Lung permeability was measured using bovine serum albumin (BSA) labeled with 125 I,and activity of pulmonary myeloperoxidase (MPO) was expressed as an index of polymorphonuclear (PMN) presence.PLA 2 and NO levels in serum or plasma,small intestine as well as lung tissues were determined at various intervals.In addition,plasma and pulmonary TNF levels in each group were also measured.Results:Treatment with rhubarb improved the hypotensive status caused by IIR( P <0 01),decreased the elevation of plasma and pulmonary TNF levels during ischemia and early stage of reperfusion.Meanwhile,rhubarb could markedly inhibit the release of endogenous NO in plasma,lung as well as intestine tissues ( P <0 05 or P <0 01),and significantly reduce the pulmonary microvascular permeability ( P <0 01).Conclusions:These results indicate that early treatment with rhubarb can prevent lung injury following IIR in rats,and such protective effect may be related to the inhibition of TNF,NO and PLA 2 release.