参附注射液对脓毒症大鼠血管内皮损伤的影响及机制  

Effect and mechanism of Shenfu injection on vascular endothelial injury in septic rats

作　　者：郭倩 刘丰进 康海[2] 郑鑫寅 GUO Qian;LIU Fengjin;KANG Hai;ZHENG Xinyin(Medical College of Qingdao University,Qingdao 266300,Shandong,China;Yantai Yuhuangding Hospital Affiliated to Qingdao University,Yantai 264000,Shandong,China)

机构地区：[1]青岛大学医学部,山东青岛266300 [2]青岛大学附属烟台毓璜顶医院,山东烟台264000

出　　处：《现代中西医结合杂志》2024年第1期60-65,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：烟台毓璜顶医院科研发展基金项目(2022-17);睿意急诊医学研究基金(22322012007);心血管多学科整合思维研究基金项目(Z-2016-23-2001-32)。

摘　　要：目的 探讨早期应用参附注射液对脓毒症大鼠血管内皮损伤的保护作用及其机制。方法 将48只成年SD雄性大鼠随机分为假手术组、脓毒症组、参附注射液组,每组16只。脓毒症组、参附注射液组大鼠采用盲肠结扎穿孔法制备脓毒症模型,假手术组仅开腹暴露盲肠后还纳腹腔。造模后参附注射液组每隔12 h腹腔注射1次参附注射液(6 mL/kg),假手术组和脓毒症组腹腔注射等体积生理盐水。观察各组大鼠术后48 h内的行为学表现,统计大鼠存活率;术后48 h处死各组存活大鼠,HE染色观察主动脉组织病理学形态,ELISA法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、组织因子(TF)、血栓调节蛋白(TM)、血管性血友病因子(vWF)、纤溶酶原激活物抑制剂-1(PAI-1)水平,Western blot法检测主动脉组织中核因子κB抑制蛋白α(IKBα)、核因子-κB(NF-κB)p65蛋白及各自磷酸化情况。结果 脓毒症组大鼠毛发束立,对外界反应迟钝,腹泻,鼻及眼部可见渗血;肠道黏膜充血水肿、坏死,光镜下显示主动脉内皮细胞增生、肿胀、脱落,内弹力膜断裂。与脓毒症组比较,参附注射液组大鼠精神和毛发状态、活动度、腹泻、鼻及眼部渗血情况、肠道水肿和坏死情况、光镜下主动脉病理改变均明显好转。术后48 h,参附注射液组大鼠存活率明显高于脓毒症组(P<0.05)。脓毒症组和参附注射液组大鼠外周血中TNF-α、IL-10、TF、TM、vWF、PAI-1水平和主动脉组中p-IKBα、p-NF-κB p65蛋白相对表达量均明显高于假手术组(P均<0.05),参附注射液组外周血中TNF-α、IL-10、TF、TM、vWF、PAI-1水平和主动脉组中p-IKBα、p-NF-κB p65蛋白相对表达量均明显低于脓毒症组(P均<0.05)。结论 早期应用参附注射液可抑制脓毒症大鼠机体炎症反应,减轻血管内皮损伤,对脓毒症导致的凝血功能障碍有一定保护作用,机制可能与抑制IKBα/NF-κB信号通路�Objective It is to investigate the protective effect of early application of Shenfu injection on vascular endothelial injury in rats with sepsis,and to explore its possible mechanism.Methods Forty-eight male SD rats were randomly divided into sham operation group,sepsis group and Shenfu injection group,with 16 rats in each group.The rats of the sepsis group and Shenfu injection group were prepared by cecum ligation and perforation to establish models of sepsis,while the rats of the sham operation group only underwent laparotomy to expose the cecal.Starting from 1 h after cecal ligation puncture,the Shenfu injection group was injected intraperitoneally with Shenfu injection(6 mL/kg)every 12 h,and the remaining two groups were injected with equal quality normal saline at the same time.The behavioral performance of rats in each group was observed in 48 h after surgery,and the survival rate of rats was counted;the surviving rats in each group were executed in 48 h after surgery,and the histopathological morphology of aortic tissue was observed by HE staining,the serum levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),tissue factor(TF),thrombomodulin(TM),von Willebrand factor(vWF),and fibrinogen activator inhibitor-1(PAI-1)were determined by ELISA,and the expressions of inhibitory subunit of NF-κBα(IκBα),nuclear factor-κB(NF-κB)p65 protein and their respective phosphorylation in aortic tissues were detected by Western blot.Results Poor hair,sluggish response to the outside world,diarrhea,blood oozing from the nose and eyes,congestion,edema and necrosis of the intestinal mucosa were found in the rats of the sepsis group,and light microscopy showed that there were hyperplasia,swelling and detachment of the aorta endothelial cells with rupture of the inner elastic membrane.Compared with the sepsis group,the mental and hair status,activity,diarrhea,blood oozing from the nose and eyes,intestinal edema and necrosis,and pathological changes of the aorta under light microscopy of the rats of the Shenfu in

关 键 词：脓毒症 炎症反应 内皮损伤 凝血功能 核因子-ΚB信号通路 

分 类 号：R-332[医药卫生]