【摘要】 目的:探讨右美托咪定对脓毒症急性肺损伤(ALI)小鼠基质金属蛋白酶7(MMP7)的抑制作用。方法:制备脓毒症致ALI模型,将昆明小鼠随机分为对照组和ALI组及治疗组,每组32只;损伤组及治疗组腹腔注射大肠杆菌脂多糖10 mg/kg,治疗组在注射脂多糖后给予腹腔注射右美托咪定25μg/kg,对照组仅注射等剂量生理盐水,并按损伤时间点分为1、3、5、8 h。到达相应时间点后,待小鼠麻醉完全后从内龇取血,低温离心留取血清备用,待测定血MMP7浓度的变化,留取右肺下叶行苏木素伊红染色,取下的肺组织放置在10%福尔马林溶液中。右肺中叶和上叶组织进行肺组织匀浆提取蛋白,左肺组织浸泡在2.5%戊二醛中待行染色。结果:治疗组炎性细胞渗出减少,ALI组肺结构破坏严重,炎性细胞渗出增多;电镜下观察肺血管内皮细胞损伤程度,治疗组血管内皮细胞损伤程度较ALI组减轻;治疗组MMP7血清浓度较ALI组降低,对照组及治疗组血清MMP7浓度均低于ALI组,各组间差异有统计学意义(P <0.01);Western结果显示,在损伤3 h时,ALI组MMP7表达较高,治疗组较ALI组相比MMP7表达下降,差异具有统计学意义(P<0.01)。结论:右美托咪定在一定程度上能抑制脓毒症ALI小鼠血清MMP7的产生。更多还原

【Abstract】 Objective:To evaluate the inhibitory effect of dexmedetomidine on matrix metalloproteinase 7(MMP7)in mice with septic acute lung injury. Methods:The sepsis-induced acute lung injury animal model was established,and KM mice were randomly divided into control group,acute lung injury(ALI)group,and treatment group,with 32 mice in each group. The mice in injury group and treatment group were injected E.coli lipopolysaccharide(LPS)10 mg/kg through intraperitoneal administration,the treatment group was given intraperitoneal injection of dexmedetomidine 25 μg/kg after lipopolysaccharide injection,and the control group was injected with the same dose of normal saline,and each group were divided into 4 subgroups according to different injury time points:1 h,3 h,5 h,8 h. After reaching the corresponding time point,when the mice were completely anesthetized,blood was taken from the inner canthus,and the serum was centrifuged at low temperature for reserve,the changes of MMP7 was measured. The lower lobe of the right lung was left for hematoxylin and eosin(HE)staining,and the lung tissue was removed and placed in 10% formalin solution. The middle and upper lobe tissues of the right lung were homogenized to extract protein,and the left lung tissue was immersed in 2.5% glutaraldehyde for electron staining. Results:In the treatment group,inflammatory cell exudation decreased,while in the ALI group,lung structure was severely damaged and inflammatory cell exudation increased. The injury of pulmonary vascular endothelial cells was observed by electron microscopy,and the injury degree of vascular endothelial cells in the treatment group was less than that in the ALI group. The serum concentration of MMP7 in the treatment group was lower than that in the ALI group. The concentration of serum MMP7 in control group and treatment group was lower than that in ALI group. There was statistically significant difference among each group(P<0.01). Western blotting showed that the expression of MMP7 was higher in ALI group at 3 h after injury. The expression of MMP7 in the treatment group was lower than that in the ALI group(P<0.01). Conclusion:Dexmedetomidine can suppress the expression of serum MMP7 in mouse model of ALI caused by sepsis to a certain extent.更多还原