川芎嗪对油酸诱导的大鼠急性肺损伤抗炎和稳定血管的作用

Effects of Ligustrazine on Anti-inflammation and Vascular Stability in Rats with Oleic Acid-induced Acute Lung Injury

目的观察川芎嗪对油酸诱导的急性肺损伤(acute lung injury,ALI)大鼠炎症反应和血管稳定性的作用。方法取60只雄性SD大鼠,随机分为对照组、川芎嗪组、油酸组和油酸+川芎嗪组,每组各15只。油酸组和油酸+川芎嗪组大鼠尾静脉注射油酸以制备ALI模型,对照组和川芎嗪组注射等量的0. 9%氯化钠注射液; 4 h后川芎嗪组和油酸+川芎嗪组大鼠腹腔注射川芎嗪,对照组和油酸组则注射等量的0. 9%氯化钠注射液; 8 h后取各组静脉血及肺组织。观察肺损伤情况,检测细胞凋亡率,记录血清炎症因子水平及对磷脂酰肌醇-3-羟激酶(phosphatidy inositol 3-kinase,PI3K)/Akt信号通路的影响。结果对照组与川芎嗪组大鼠肺组织结构完整,肺泡腔清晰;油酸组与油酸+川芎嗪组大鼠肺泡腔内有炎性因子浸润,肺组织水肿,且油酸组肺损伤更严重。与对照组比较,油酸组、油酸+川芎嗪组细胞凋亡率、白细胞介素(IL)-6、诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、IL-1β及Caspase-9表达水平明显升高,血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)、磷酸化-PI3K(p-PI3K)/PI3K和p-Akt/Akt的表达水平降低,差异有统计学意义(P <0. 01);与油酸组比较,油酸+川芎嗪组细胞凋亡率、IL-6、i NOS、TNF-α、IL-1β及Caspase-9表达水平显著降低,VEGF、VEGFR2、p-PI3K/PI3K和p-Akt/Akt的表达水平明显升高,差异有统计学意义(P <0. 01)。结论川芎嗪通过促进PI3K/Akt通路激活以抑制ALI大鼠肺组织炎症反应,促进血管稳定。

Objective To investigate the effects of ligustrazine(LGT)on inflammatory response and vascular stability of rats with oleic acid-induced acute lung injury(ALI).Methods A total of60SD male rats were divided into control group,LGT group,oleic acid group and oleic acid+LGT group,with15rats in each group.The rats in oleic acid group and oleic acid+LGT group were injected with oleic acid(0.9mL/kg)to establish lung acute injury model of rats.Those in control group and LGT group were injected with0.9%sodium chloride injection.After treatment with OA for4h,rats in LGT group and oleic acid+LGT group were intraperitoneally injected with0.6%LGT(10mL/kg),while those in control group and oleic acid group were injected with0.9%sodium chloride injection.After treatment with LGT for8h,the venous blood and lung tissues of each group were collected.The lung injury was observed,the apoptosis rate was measured,and the serum inflammatory factor level and the influence on phosphatidy inositol3-kinase(PI3K/Akt)signaling pathway were recorded.Results There was intact lung tissue and clear alveolar cavity in control group and LGT group.Inflammatory factor infiltration in the alveolar cavity and lung tissue edema were found in oleic acid group and oleic acid+LGT group,in addition to more serious lung injury in the oleic acid group.Compared with control group,the cell apoptosis rate,the level of interleukin(IL)-6,inducible nitric oxide synthase(iNOS),tumor necrosis factor(TNF)-α,IL-1βand Caspase-9in oleic acid group and oleic acid+LGT group were increased significantly,while the protein level of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor2(VEGFR2),the ratio of p-PI3K/PI3K and p-Akt/Akt were decreased markedly.The significant differences were observed(P<0.01).Compared with oleic acid group,the cell apoptosis rate,the level of IL-6,iNOS,TNF-α,IL-1βand Caspase-9in oleic acid+LGT group were down-regulated markedly,whereas the protein level of VEGF,VEGFR2,the ratio of p-PI3K/PI3K and p-Akt/Akt in oleic acid+LGT group were up-regulated notably,suggesting significant differences(P<0.01).Conclusion LGT inhibits inflammation and promotes vascular stability of ALI rats by activating PI3K/Akt pathway.