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目的研究白藜芦醇(Resveratrol,Res)对脓毒症大鼠急性肺损伤(Acute lung injury,ALI)的保护作用及对ALI大鼠肺组织中巨噬细胞炎症蛋白-2(Macrophage inflammatory protein,MIP-2)、白细胞介素-10(Interleukin-10,IL-10)和白细胞介素-18(Interleukin-18,IL-18)表达的影响。方法将SD大鼠随机分为空白对照组(Con组)、假手术组(Sham组)、脓毒症组(Sep组)和白藜芦醇组(Res组)。采用盲肠结扎穿刺术(Cecal ligation and puncture,CLP)制备脓毒症相关性ALI大鼠模型,造模24 h后,Res组给予0.3 ml/100 g的Res液,Con、Sham和Sep组给予等量生理盐水,均经尾静脉注射。各组分别于0、6、12、24和48 h,取大鼠肺组织,HE染色观察病理形态学变化,计算肺湿重/干重比值(W/D);ELISA法检测各组大鼠血浆中MIP-2、IL-10和IL-18含量;Western blot法检测各组大鼠肺组织中MIP-2、IL-10和IL-18蛋白的表达水平。结果 Res组在造模后12 h,肺组织病理变化与Sep组相比有所减轻,48 h Res作用达到最强,各种病理改变明显减轻,部分肺组织开始接近正常形态;肺组织W/D比值与Sep组相比均明显降低(P<0.05);Res组在12、24和48 h MIP-2水平均明显低于同时间点Sep组(P<0.05),在24和48 h IL-10水平明显低于同时间点Sep组(P<0.05),12、24和48 h IL-18水平明显低于同时间点Sep组(P<0.05)。Western blot结果显示,造模后24 h,Res组MIP-2、IL-10和IL-18蛋白表达水平明显低于Sep组(P<0.05)。结论白藜芦醇能有效减轻脓毒症所致ALI,作用与抑制MIP-2、IL-10和IL-18的过度表达,实现内稳态有关。
Objective To investigate the protective effect of resveratrol on acute lung injury (ALI) in septic rats and the effect of macrophage inflammatory protein-2 MIP-2), Interleukin-10 (IL-10) and interleukin-18 (IL-18) Methods SD rats were randomly divided into control group (Con group), sham operation group (Sham group), sepsis group (Sep group) and resveratrol group (Res group). The sepsis-related ALI rat model was established by cecal ligation and puncture (CLP). Res 24 hours after the model was established, Res group was given 0.3 ml / 100 g of Res solution, Con, Sham group and Sep group The amount of saline, all via tail vein injection. The rats were sacrificed at 0, 6, 12, 24 and 48 h respectively. The lung tissues of rats were taken out and the pathological changes were observed by HE staining. W / D (W / D) The levels of MIP-2, IL-10 and IL-18 in plasma were detected by Western blot. The expression of MIP-2, IL-10 and IL-18 in lung tissues of rats in each group were detected by Western blot. Results In the Res group, the pathological changes of lung tissue were relieved at 12 h after modeling compared with those in the Sep group. The Res reached the strongest effect at 48 h and all pathological changes were alleviated. Some of the lung tissues began to approach the normal morphology. The W / (P <0.05). The levels of MIP-2 in Res group were significantly lower than those in Sep group at 12, 24 and 48 h (P <0.05) -10 levels were significantly lower than those in the Sep group at the same time point (P <0.05). The IL-18 levels at 12, 24 and 48 h were significantly lower than those in the Sep group at the same time point (P <0.05). Western blot results showed that the expression of MIP-2, IL-10 and IL-18 in Res group was significantly lower than that in Sep group (P <0.05) 24 h after model establishment. Conclusion Resveratrol can effectively reduce the ALI induced by sepsis and its effect is related to the inhibition of the overexpression of MIP-2, IL-10 and IL-18 to achieve the homeostasis.