【摘要】 目的 观察丹参酮ⅡA磺酸钠(sodium tanshinoneⅡA sulfonate,STS)对百草枯中毒大鼠血清肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白三烯B4(leukotriene B4,LTB4)浓度、肺组织5-脂氧化酶(5-lipoxygenase,5-LOX)蛋白及mRNA表达的影响。方法 75只Sprague-Dawley(SD)雄性大鼠随机分成对照组、百草枯组、STS组,每组25只。对照组腹腔注射生理盐水2 mL,百草枯组给予生理盐水稀释百草枯50 mg/kg至2 mL灌胃染毒,STS组在百草枯染毒后给予STS25 mg/kg腹腔注射,连续注射3 d。各组分别于制模后72 h处死大鼠,心脏取血;腹主动脉取血行血气PO2检测;留取肺组织标本,采用HE染色,光镜下观察肺组织病理变化;酶联免疫法检测血清TNF-α、IL-6及LTB4浓度;Western blot检测5-LOX蛋白表达量;实时荧光定量PCR法检测5-LOX mRNA表达量。结果 ①HE染色对照组大鼠肺组织结构清晰,肺泡无水肿;百草枯组大鼠肺内大量的炎性细胞浸润,肺间隔水肿断裂;STS组大鼠肺间质及肺泡充血水肿明显减轻,少量炎性细胞浸润。②百草枯组(52.76±3.85)mm Hg及STS组(69.12±4.52)mm Hg大鼠动脉血气PO2均显著低于对照组(86.45±5.23)mm Hg(P<0.01);STS组动脉血气PO2显著高于百草枯组(P<0.01)。③百草枯组及STS组大鼠血清TNF-α、IL-6、LTB4浓度显著高于对照组(P<0.01);STS组大鼠血清TNF-α、IL-6、LTB4浓度显著低于百草枯组(P<0.01)。④百草枯组(0.978±0.045)大鼠肺组织5-LOX蛋白表达量均显著高于对照组(0.780±0.022)及STS组(0.712±0.065)(P<0.01);而STS组大鼠肺组织5-LOX蛋白表达量低于对照组(P<0.05)。⑤百草枯组(3.241±0.330)及STS组(2.045±0.234)大鼠肺组织5-LOX mRNA表达量均显著高于对照组(1.332±0.118)(P<0.01);STS组大鼠肺组织5-LOX mRNA表达量显著低于百草枯组(P<0.01)。结论 STS可能通过抑制5-LOX表达和LTB4的释放,减轻炎症级联反应,防止百草枯中毒大鼠肺损伤发生。更多还原

【Abstract】 Objective To investigate the effects of sodium tanshinone ⅡA sulfonate（ STS） on serum level about tumor necrosis factor-α（TNF-α）, interleukin-6（ IL-6） and leukotriene B4（LTB4） and 5-lipoxygenase protein and mRNA expression in paraquat poisoning rats lung. Methods Sprague-Dawley（ SD） male rats were randomly divided into control group, paraquat group, STS group. Each group was made up of 25 rats. Rats in control group were injected by 2 mL intraperitoneal injection of saline. Rats in paraquat group were given saline diluting paraquat 50 mg/kg to 2 mL lavage infected. Rats in STS group were given 25 mg/kg STS by intraperitoneal injection after paraquat poisoning, and were injected continuously for three days. After the model was completed 72 h groups rats were executed respectively. The heart was taken, and the abdominal aorta blood was collected for PO₂inspection. The lung tissue specimens were stained by turbulence eosin（HE） staining, and then were observed the lung tissue pathology. The serum concentration of TNF-α, IL-6 and LTB4 was detected by enzyme-linked immunoassay. 5-LOX protein expression was detected by Western blotting testing.5-LOX mRNA expression was detected by real-time fluorescent quantitative PCR. Results ①It can be seen that lung tissue structure is clear, pulmonary interstitial and alveolar was normal in the control group. In paraquat group, a large number of inflammatory cells infiltrated in the rat lungs, and pulmonary became edema and pulmonary interstitial fractured. In STS group, rat pulmonary interstitial and alveolar congestion edema relieved obviously, a small amount of inflammatory cell infiltrated.②Rat arterial blood gas PO₂ was significantly lower in paraquat and STS groups than that in control group（P <0.01）. In STS group, arterial blood gas PO₂ was significantly higher than that in paraquat group（P <0.01）.③In paraquat and STS group, serum concentration of TNF-α, IL-6 and LTB4 was significantly higher than that in control group（P <0. 01）. In STS group, serum concentration of TNF-α, IL-6 and LTB4 was significantly lower than that in paraquat group（P < 0. 01）.④In paraquat group, the amount of 5-LOX protein expression in rat lung tissue was significantly higher than that in control group and the STS group（ P < 0. 01）. In STS group, 5-LOX protein expression in rat lung tissue was lower than that in control group（P < 0.05）. ⑤In paraquat and STS group, 5-LOX mRNA expression in rat lung tissue was significantly higher than that in control group（ P < 0. 01）. In STS group, 5-LOX mRNA expression in rat lung tissue was significantly lower than that in paraquat group（P <0. 01）. Conclusion STS may restrain 5-LOX expression to inhibit LTB4 releasing, reducing inflammation cascade reaction. STS may suppress lung injury in rats of paraquat poisoning.更多还原