丹参酮ⅡA磺酸钠对环境细颗粒物所致大鼠肺部炎性损伤的影响

Intervention effect of sulfotanshinone ⅡA sodium on lung inflammation induced by ambient fine particulate matters in rats

[背景]吸入环境细颗粒物(PM_(2.5))易造成机体肺部炎性损伤,寻找有效的干预物质十分必要。[目的]研究丹参酮ⅡA磺酸钠(TanⅡA)对PM_(2.5)所致大鼠肺部炎性损伤的影响。[方法]健康SD雄性大鼠,随机分为4组,每组6只,分别为对照组、模型组、TanⅡA组,地塞米松阳性对照组。采用气管滴注细颗粒物建立大鼠肺部炎症模型。除对照组气管滴注生理盐水外,其他组均按5.4 mg·kg^(-1)行气管滴注PM_(2.5)悬液染毒,每3 d 1次,共10次;除给予滴注染毒外,TanⅡA组以15 mg·kg^(-1)TanⅡA,地塞米松阳性对照组以0.5 mg·kg^(-1)地塞米松,从染毒第1天起,每天1次腹腔注射,持续28 d;最后1次染毒后2 d内处死。比较各组大鼠体重,光镜下观察各组肺组织形态变化,检测肺泡灌洗液中白细胞计数和中性粒细胞、嗜酸性粒细胞百分比,以及总蛋白质量浓度和碱性磷酸酶、乳酸脱氢酶活性。[结果]染毒结束时,与对照组相比,模型组大鼠体重降低(P<0.01);肺组织病理可见黑色细颗粒物沉积于肺泡隔,沉积部分局灶性多量炎性细胞浸润,肺间隔增宽,肺泡闭锁等损伤;肺泡灌洗液中白细胞数量升高[(2.46±0.74)×10^(6) mL^(-1) vs(0.91±0.51)×10^(6) mL^(-1)](P<0.01),中性粒细胞、嗜酸性粒细胞百分比升高,分别为[(45.2±10.3)%vs(24.7±7.5)%、(5.7±2.7)%vs(2.0±1.4)%](均P<0.01),总蛋白质量浓度和碱性磷酸酶、乳酸脱氢酶活性升高,分别为[(0.4±0.1)g·L^(-1) vs(0.2±0.1)g·L^(-1)、(65.4±6.5)U·L^(-1) vs(43.1±10.5)U·L^(-1)、(151.4±29.0)U·L^(-1) vs(82.5±18.5)U·L^(-1)](均P<0.01)。与模型组相比,TanⅡA组大鼠体重升高(P<0.05);光镜下仅可见少量炎性细胞,肺泡壁结构紊乱、肺间隔增厚程度与模型组相比均较轻;肺泡灌洗液中白细胞数量降低[(1.14±0.48)×10^(6) mL^(-1) vs(2.46±0.74)×10^(6) mL^(-1)](P<0.01),中性粒细胞、嗜酸性粒细胞百分比降低,分别为[(32.3±6.1)%vs(45.2±10.3)%、(2.8±1.8)%vs(5.7±2.7)%](均P<0.05),总蛋白质量浓度和碱性磷酸酶、乳酸脱氢酶活性降低[(0.2±0.1)g·L^(-1) vs(0.4±0.1)g·L^(-1)、(50.9±3.0)U·L^(-1) vs(65.4±6.5)U·L^(-1)、(97.4±12.8)U·L^(-1) vs(151.4±29.0)U·L^(-1)](P<0.05,P<0.01)。TanⅡA组各项指标与对照组及地塞米松阳性对照组比较差异无统计学意义(均P>0.05)。[结论]TanⅡA能减轻PM_(2.5)导致的大鼠肺部炎性损伤。

[Background] Inhaling ambient fine particulate matters(PM_(2.5)) can cause inflammatory damage to the lungs, so it is necessary to find a medicine for effective intervention.[Objective] This experiment investigates the intervention effect of sulfotanshinoneⅡA sodium(TanⅡA) on lung inflammation induced by ambient PM_(2.5) in rats.[Methods] Healthy male SD rats were randomly divided into four groups, with six rats in each group: control group, model group, TanⅡA group, and dexamethasone positive control group. A rat lung inflammation model was established by tracheal instillation of PM_(2.5). Each group except the control group was exposed to PM_(2.5)(5.4 mg·kg^(-1)) once every three days for a total of 10 times. The rats of the TanⅡA group(15 mg·kg^(-1) TanⅡA) and the dexamethasone positive control group(0.5 mg·kg^(-1) dexamethasone), from the first day of exposure, were treated by intraperitoneal injection once a day for 28 days. All rats were neutralized within two days after the last exposure. The body weight, morphological changes of lung tissues, the counts of leukocytes, the proportions of neutrophils and eosinophils, the concentration of total protein, and the activities of alkaline phosphatase and lactate dehydrogenase in bronchoalveolar lavage fluid were detected. [Results] Compared with the control group, after designed treatment, the body weight of the model group decreased(P < 0.01);the pathological results of lung tissues showed black fine particles deposited in alveolar septum, along with focal inflammatory cell infiltration, pulmonary septal broadening, alveolar atresia, and other injuries;the number of leukocytes [(2.46±0.74)×10^(6) mL^(-1) vs(0.91±0.51)×10^(6) mL^(-1)](P < 0.01), the proportions of neutrophils and eosinophils [(45.2±10.3)% vs(24.7±7.5)%,(5.7±2.7)% vs(2.0±1.4)%](both P < 0.01), the concentration of total protein, and the activities of alkaline phosphatase and lactate dehydrogenase [(0.4±0.1) g·L^(-1) vs(0.2±0.1) g·L^(-1),(65.4±6.5) U·L^(-1) vs(43.1±10.5) U·L^(-1), and(151.4±29.0) U·L^(-1) vs(82.5±18.5) U·L^(-1)](all P < 0.01) increased. Compared with the model group, the body weight of the Tan IIA group increased(P < 0.05);under light microscope, few inflammatory cells were observed, and the degree of injury such as disordered alveolus and thickened alveolar septum was alleviated;and the number of leukocytes [(1.14±0.48)×10^(6) mL^(-1) vs(2.46±0.74)×10^(6) mL^(-1)](P < 0.01), the proportions of neutrophils and eosinophils [(32.3±6.1)% vs(45.2±10.3)%,(2.8±1.8)% vs(5.7±2.7)%](both P < 0.05), and the concentration of total protein, and the activities of alkaline phosphatase and lactate dehydrogenase [(0.2±0.1) g·L^(-1) vs(0.4±0.1) g·L^(-1),(50.9±3.0) U·L^(-1) vs(65.4±6.5) U·L^(-1), and(97.4±12.8) U·L^(-1) vs(151.4±29.0) U·L^(-1)](P < 0.05, P < 0.01) decreased. There were no significant differences in the above-mentioned indexes between the TanⅡA group and the control group or the dexamethasone positive control group(all P > 0.05).[Conclusion] TanⅡA may reduce the lung inflammation induced by PM_(2.5) in rats.