摘要
目的:探索川芎嗪对内毒素诱导的急性肺损伤大鼠肺纤维化和炎症反应的影响及其机制。方法:大鼠随机分为5组:对照组、LPS模型组、LPS+川芎嗪(50,100,200mg·kg^(-1))组。苏木素伊红(HE)染色观察肺组织病变。Masson染色分析肺纤维化。酶联免疫吸附实验(ELISA)检测白细胞介素(interleukin,IL)-6,IL-1β,肿瘤坏死因子(tTNF-α)和IL-18水平。蛋白印记检测α平滑肌肌动蛋白(α-SMA),转化生长因子β1(TGF-β1),Ⅰ型胶原蛋白(collagen typeⅠ),Ⅲ型胶原蛋白(col-lagen typeⅢ),PI3K,P-PI3K,AKT,P-AKT,mTOR和P-mTOR的蛋白水平。结果:LPS模型组大鼠肺组织湿/干重之比高于对照组(P<0.01)。与LPS模型组相比,LPS+川芎嗪(100,200mg·kg^(-1))组大鼠肺组织湿/干重之比降低(P<0.01)。川芎嗪处理可改善LPS模型组大鼠肺组织病变及纤维化。LPS模型组大鼠α-SMA,TGF-β1,collagen typeⅠ和collagen typeⅢ表达高于对照组(P<0.01)。与LPS模型组相比,LPS+川芎嗪(50,100,200mg·kg^(-1))组大鼠α-SMA、TGF-β1、collagentypeⅠ和collagen typeⅢ表达降低(P<0.01)。与对照组相比,LPS模型组大鼠IL-6、IL-1β、IL-18和TNF-α水平升高(P<0.01)。LPS+川芎嗪(50,100,200mg·kg^(-1))组大鼠IL-6、IL-1β、IL-18和TNF-α水平低于LPS模型组(P<0.01)。LPS模型组大鼠P-PI3K/PI3K,P-AKT/AKT和P-mTOR/mTOR比值高于对照组(P<0.01)。与LPS模型组相比,LPS+川芎嗪(50,100,200mg·kg^(-1))组大鼠P-PI3K/PI3K,P-AKT/AKT和P-mTOR/mTOR比值下降(P<0.01)。结论:川芎嗪可通过抑制PI3K/AKT/mTOR信号通路活化减轻内毒素诱导的急性肺损伤大鼠肺纤维化和炎症反应。
OBJECTIVE To explore the effect of ligustrazine on pulmonary fibrosis and inflammatory response in acute lung injury induced by endotoxin.METHODS Rats were randomly divided into five groups,including control group,LPS modelgroup and LPS+ligustrazine(50,100,200 mg·kg-1)groups.Pathological changes of lung tissues were observed by hema-toxylin-eosin(HE)staining.Fibrosis of lung tissues was analyzed by Masson staining.The levels of interleukin(IL)-6,IL-1β,tumor necrosis factor(TNF-α)and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA).The protein levels ofα-smooth muscle-actin(α-SMA),transforming growth factor-β1(TGF-β1),collagen typeⅠ,collagen typeⅢ,PI3 K,P-PI3 K,AKT,P-AKT,mTOR and P-mTOR were measured by Western blot.RESULTS The rate of wet weight/dry weight(W/D)in LPS model group was higher than that of control group(P<0.01).Compared with LPS model group,the rates ofW/D in LPS+ligustrazine(100,200 mg·kg-1)groups were decreased(P<0.01).The pathological changes and fibrosis oflung tissues were ameliorated by ligustrazine.The expressions ofα-SMA,TGF-β1,collagen typeⅠand collagen typeⅢinLPS model group were higher than those of control group(P<0.01).Compared with LPS model group,the expressions ofα-SMA,TGF-β1,collagen typeⅠand collagen typeⅢin LPS+ligustrazine(50,100,200 mg·kg-1)groups were reduced(P<0.01).Compared with control group,the levels of IL-6,IL-1β,IL-18 and TNF-αin LPS model group were increased(P<0.01).The levels of IL-6,IL-1β,IL-18 and TNF-αin LPS+ligustrazine(50,100,200 mg·kg-1)groups were lower thanthose in LPS model group(P<0.01).The rates of P-PI3 K/PI3 K,P-AKT/AKT and P-mTOR/mTOR in LPS model groupwere higher than those of control group(P<0.01).Compared with LPS model group,the rates of P-PI3 K/PI3 K,P-AKT/AKT and P-mTOR/mTOR in LPS+ligustrazine(50,100,200 mg·kg-1)groups were decreased(P<0.01).CONCLUSIONLigustrazine alleviates the fibrosis and inflammatory response by inhibiting activation of PI3 K/AKT/mTOR pathway in endotoxin-induced acute lung injury rats.
作者
张娟娟
胡仕祥
李华
郭燕可
刘寒阳
ZHANG Juan-juan;HU Shi-xiang;LI Hua;GUO Yan-ke;LIU Han-yang(Department of Emergency Intensive Medicine,Henan Traditional Chinese Medicine Hospital,The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine,Henan Zhengzhou 450002,China)
出处
《中国医院药学杂志》
CAS
北大核心
2019年第3期259-264,共6页
Chinese Journal of Hospital Pharmacy
