尼群地平对大鼠肺缺血再灌注损伤后TNF-α、IL-6和IL-8变化的影响

Therapeutic effects of nitrendipine on early pulmonary ischemia/reperfusion injury in rats

目的：观察尼群地平（Ｎｉｔｒｅｎｄｉｐｉｎｅ）对大鼠早期肺缺血再灌注损伤的防治作用和可能的机制。方法：将７２只大鼠随机分为手术对照组（ＯＣ）、肺缺血再灌注损伤组（ＩＲ）和尼群地平处理组（ＮＴ），采用肺在体缺血再灌注模型，动态测定肺组织和血浆肿瘤坏死因子－α（ＴＮＦ－α）、白介素－６（ＩＬ－６）、白介素－８（ＩＬ－８）、肺组织总钙、肺组织干／湿重比值（Ｄ／Ｗ）和肺静态顺应性（Ｃｓｔ）变化。结果：肺缺血再灌注损伤早期肺组织总钙水平升高，肺组织ＴＮＦ－α、ＩＬ－６和ＩＬ－８相继释放增加并与肺Ｄ／Ｗ、肺Ｃｓｔ下降呈显著相关性。尼群地平处理后，肺组织总钙和ＴＮＦ－α、ＩＬ－６、ＩＬ－８水平显著降低（Ｐ＜０．０５和Ｐ＜０．０１），肺Ｄ／Ｗ升高，肺Ｃｓｔ改善。结论：尼群地平可通过阻滞钙通道，减少细胞钙内流，抑制炎性细胞因子释放，减轻肺缺血再灌注损伤。

Objective: To determine the therapeutic effects of nitrendipine on early pulmonary ischemia/reperfusion injury and to explore its possible mechanism. Methods: Seventy two rats were randomized into the opetation control group (OC), pulmonary ischemia/reperfusion injury group (IR) and nitrendipine treated group (NT). The animals in IR were inflicted on pulmonary ischemia/reperfusion injury through occlusion of left lung hilus for 45 min while those in NT were inflicted on the same injury and treated with nitrendipine. The dynamic changes of tumor necrosis factor α (TNF α), interleukin 6 (IL 6) and interleukin 8 (IL 8) in both the pulmonary tissue and plasma were observed. The total calcium level of the pulmonary tissue, dry wet weight ratios of the lung tissue (D/W) and static lung compliance (Cst) were also measured during pulmonary ischemia/reperfusion. Results: As compared with OC, the levels of TNF α, IL 6, IL 8 and total calcium in the pulmonary tissue in IR were significantly increased ( P <0.05 and 0.01). These four parameters and D/W and Cst were correlated to one another. In NT, the four parameters were markedly decreased ( P <0.05 and 0.01). Conclusion: Nitrendipine can reduce Ca 2+ influx of the cells by blocking dihydropyridine sensitive calcium channel to inhibit the release of inflammatory cytokines. Therefore, it can alleviate the pulmonary ischemia/reperfusion injury.