扶正解毒颗粒对脂多糖致急性肺损伤小鼠的保护作用与机制研究

Protective Effect and Mechanism of Fuzheng Jiedu Granules on Lipopolysaccharide-induced Acute Lung Injury in Mice

目的探讨扶正解毒颗粒(淡附片、金银花、五指毛桃、广藿香等)对脂多糖致急性肺损伤小鼠的作用及机制。方法将72只雄性KM小鼠随机分成正常组、模型组、醋酸泼尼松片组(10 mg·kg^(-1))及扶正解毒颗粒低、中、高剂量组(7.5、15、30 g·kg^(-1)),灌胃给药,每日1次,连续2周。采用脂多糖咽后壁滴注建立急性肺损伤小鼠模型。计数肺泡灌洗液中的细胞总数及中性粒细胞数;采用HE染色法观察肺组织病理变化并进行病理学评分;检测肺组织匀浆中的白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量。将60只KM小鼠(雌雄各半)随机分成空白组、醋酸泼尼松片组(10 mg·kg^(-1))及扶正解毒颗粒低、中、高剂量组(7.5、15、30 g·kg^(-1)),灌胃给药,每日1次,连续2周。测定小鼠碳粒廓清指数及吞噬指数。结果与正常组比较,模型组小鼠支气管肺泡灌洗液中的细胞总数和中性粒细胞显著升高(P<0.01),肺组织匀浆中的IL-1β、IL-6、TNF-α含量显著升高(P<0.01),肺组织病理学评分显著增高(P<0.01)。与模型组比较,扶正解毒颗粒组小鼠支气管肺泡灌洗液中的细胞总数有不同程度降低(P<0.05);小鼠肺组织匀浆中的IL-1β、IL-6含量明显降低(P<0.05,P<0.01);肺组织病理评分显著降低(P<0.01)。与空白组比较,扶正解毒颗粒组小鼠的碳粒廓清指数和吞噬指数明显降低(P<0.05)。结论扶正解毒颗粒能在一定程度上抑制脂多糖诱导的小鼠急性肺损伤,改善肺组织病理学变化,其作用机制可能与抑制炎性细胞因子(IL-1β、IL-6)的分泌发挥抗炎作用以及抑制非特异性免疫作用有关。

Objective To investigate the effect and mechanism of Fuzheng Jiedu Granules on lipopolysaccharideinduced acute lung injury(ALI)mice.Methods Seventy-two male KM mice were randomly divided into the normal group,the model group,the Prednisone Acetate Tablets group(10 mg·kg^(-1))and the low-,medium-and highdose of Fuzheng Jiedu Granules groups(7.5,15 and 30 g·kg^(-1)),which were administered by gavage once daily for 2 continuous weeks.A mouse model of ALI was established by using lipopolysaccharide posterior pharyngeal wall drip injection.The total number of cells and neutrophils in the alveolar lavage fluid were counted;the lung histopathological changes were observed by the HE staining and scored pathologically;the interleukin 1β(IL-1β),the interleukin 6(IL-6)and tumour necrosis factorα(TNF-α)levels in lung tissue homogenates were measured.Sixty KM mice(half male and half female)were randomly divided into the normal group,the Prednisone Acetate Tablets group(10 mg·kg^(-1))and the low-,medium-and high-dose of Fuzheng Jiedu Granules group(7.5,15 and 30 g·kg^(-1)),which were administered by gavage once daily for 2 continuous weeks.The carbon particle contouring index and phagocytosis index of mice were measured.Results Compared with the normal group,the total number of cells and neutrophils in the bronchoalveolar lavage fluid of mice in the model group were significantly increased(P<0.01),and the contents of IL-1β,IL-6 and TNF-αin the lung tissue homogenate were significantly increased(P<0.01),and the histopathological score of lung was significantly increased(P<0.01).Compared with model group,the total number of cells in bronchoalveolar lavage fluid of mice in the Fuzheng Jidu Granules group were decreased to different degrees(P<0.05);The contents of IL-1βand IL-6 in lung tissue homogenate of mice were significantly decreased(P<0.05,P<0.01).The pathological score of lung tissue was significantly decreased(P<0.01).Compared with the blank group,the carbon clearance index and phagocytosis index of Fuzheng Jiedu Granules group were significantly decreased(P<0.05).Conclusion Fuzheng Jiedu Granules can inhibit lPS-induced ALI to a certain extent and improve the histopathological changes of lung.The mechanism of action may be related to inhibiting the secretion of inflammatory cytokines(IL-1β,IL-6)and inhibiting the non-specific immune function.