盐酸小檗碱对脓毒症诱导急性呼吸窘迫综合征小鼠的保护作用及机制研究  

Study on the protective effects and mechanism of berberine hydrochloride on sepsis induced acute respiratory distress syndrome in mice

作　　者：武晓灵 喻莉[1] 龙鼎 杨军辉 WU Xiaoling;YU Li;LONG Ding;YANG Junhui(Intensive Care Unit,The Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430014,China)

机构地区：[1]华中科技大学附属武汉中心医院重症医学科

出　　处：《实用医学杂志》2019年第22期3452-3456,共5页The Journal of Practical Medicine

基　　金：湖北省科技计划项目(编号:2017CFC851)

摘　　要：目的观察盐酸小檗碱(berberine,BBR)对脓毒症诱导急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)小鼠的保护作用及机制。方法将54只野生型C57BL/6小鼠随机分为对照组、脂多糖(lipopolysaccharide,LPS)组、脂多糖+盐酸小檗碱(LPS+BBR)组,每组各18只。脓毒症ARDS小鼠模型采用LPS诱导构建,试验组用BBR进行干预。肺组织切片HE染色观察肺损伤程度,并计算肺湿/干重比值;各炎症因子的表达水平用ELISA、实时荧光定量PCR方法检测;p65和p-P65的蛋白水平采用蛋白免疫印迹法(WB)检测。结果 LPS可成功诱导脓毒症ARDS小鼠模型。LPS+BBR组小鼠肺组织损伤较LPS组明显减轻,微血管内只有少量充血和出血,肺泡腔和肺间质仅少量炎性渗出,肺泡间隔也明显变薄。LPS组肺组织损伤评分大于LPS+BBR组及对照组,LPS组肺组织湿/干重比值大于LPS+BBR组及对照组(均P <0.05)。炎症因子TNF-α、IL-6的水平LPS组大于LPS+BBR组及对照组(P <0.05),抗炎因子IL-10的水平LPS组小于LPS+BBR组及对照组(P <0.05),LPS+BBR组NF-κB p65的表达水平较LPS组明显降低(P <0.05)。结论盐酸小檗碱可以减轻LPS诱导的小鼠肺组织的炎症反应和损伤,可能的机制为抑制肺组织中NF-κB信号通路的异常激活。Objective To observe the protective effect and mechanism of berberine hydrochloride on sepsis-induced acute respiratory distress syndrome(ARDS)mice. Methods 54 wild-type C57BL/6 mice were randomly divided into control group,lipopolysaccharide(LPS)group,lipopolysaccharide + berberine hydrochloride(LPS+BBR)group with 18 in each group. The mouse model of sepsis ARDS was induced by LPS,and BBR was intervened. The degree of lung injury was observed by HE staining,and the ratio of lung wet/dry weight was calculated. The expression levels of each inflammatory factor were detected by ELISA and real-time fluorescent quantitative PCR. The protein levels of P65 and p-P65 were detected by Western Blot(WB). Results LPS can successfully induce sepsis ARDS mouse model. The LPS+BBR group had significantly less lung tissue damage than the LPS group. There was only a small amount of congestion and hemorrhage in the microvessels. and a small amount of inflammatory exudation in the alveolar space and interstitial lung,and the alveolar septum was also significantly thinner. The lung tissue injury score of LPS group was higher than that of LPS+BBR group and the control group. The wet/dry weight ratio of LPS group was higher than that of the LPS+BBR group and the control group(P < 0.05).The levels of inflammatory factors TNF-α and IL-6 were higher in LPS group than in LPS+BBR group and the control group(P < 0.05). The level of anti-inflammatory factor IL-10 was lower in the LPS group than in the LPS+BBR group and the control group(P < 0.05). The expression level of NF-κB p65 in LPS+BBR group was significantly lower than that in LPS group(P < 0.05). Conclusions Berberine hydrochloride can alleviate the LPS-induced inflammatory response and injury in mouse lung tissue,and the possible mechanism is to inhibit the abnormal activation of NF-κB signaling pathway in lung tissue.

关 键 词：急性呼吸窘迫综合征 盐酸小檗碱 炎症反应 脓毒症 

分 类 号：R28[医药卫生—中药学]