血必净注射液对脓毒症大鼠内皮微粒及肾脏皮质微循环的影响

来源 :中华危重病急救医学 | 被引量 : 0次 | 上传用户:Ivy1234
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
目的:明确脓毒症大鼠肾脏皮质微循环特点及其与血浆内皮微粒(EMP)表达之间的关系,评价血必净注射液作为抗菌药物辅助治疗的干预效果。方法:将8~10周龄无特定病原体(SPF)级雄性SD大鼠按随机数字表法分为假手术组(Sham组)、阳性药物对照组和血必净组,每组10只。采用高位结扎的盲肠结扎穿孔术(CLP)制备脓毒症大鼠模型;Sham组只翻动盲肠,不进行结扎穿孔。基于高位结扎CLP致死率高,血必净组于制模后即刻经尾静脉注射血必净注射液4 mL/kg、12 h 1次,亚胺培南/西司他丁注射液90 mg/kg、6 h 1次;阳性药物对照组以相同方法给予生理盐水和亚胺培南/西司他丁注射液;Sham组给予等量生理盐水以相同频次进行干预。术后48 h记录大鼠平均动脉压(MAP)和血乳酸(Lac);应用测流暗场成像技术监测肾脏皮质微循环血流;采用哌莫硝唑免疫组化法评估肾组织缺氧程度;应用流式细胞仪检测血浆EMP水平,并分析EMP与肾脏皮质微循环灌注指标的相关性;同时测量血肌酐(SCr),并采用肾组织损伤评分(Paller评分)评价肾组织病理损伤严重程度。结果:与Sham组相比,阳性药物对照组和血必净组大鼠灌注血管密度(PVD)、微血管流动指数(MFI)和MAP均明显下降,缺氧指示剂哌莫硝唑阳性表达明显增加,Lac、EMP、Paller评分和SCr均明显升高。但与阳性药物对照组比较,血必净组大鼠肾脏皮质微循环血流明显改善,PVD和MFI显著升高〔PVD(mm/mmn 2):16.20±1.20比9.77±1.12,MFI:2.46±0.05比1.85±0.15,均n P<0.05〕,Lac水平明显降低(mmol/L:4.81±1.23比6.08±1.09,n P0.05〕,提示血必净注射液可改善脓毒症大鼠肾脏皮质微循环灌注,而这种效应不依赖于MAP的改变。血必净组肾脏皮质哌莫硝唑阳性表达量较阳性药物对照组明显降低〔(35.89±1.13)%比(44.93±1.37)%,n P<0.05〕,提示血必净注射液能减轻脓毒症大鼠肾脏缺氧程度。血必净组大鼠血浆EMP水平较阳性药物对照组显著降低(×10n 6/L:3.49±0.17比5.78±0.22,n P<0.05),且EMP水平与PVD和MFI均呈显著负相关(n r值分别为-0.94和-0.95,均n P<0.05),提示脓毒症大鼠血浆EMP水平升高与肾脏皮质微循环障碍高度相关,血必净注射液能抑制EMP的产生。血必净组Paller评分较阳性药物对照组显著降低(分:46.90±3.84比62.70±3.05,n P<0.05),SCr水平亦明显低于阳性药物对照组(μmol/L:121.1±12.4比192.7±23.9,n P<0.05),提示血必净注射液能减轻脓毒症大鼠肾损伤程度,改善肾功能。n 结论:作为抗菌药物的辅助治疗,血必净注射液可抑制脓毒症大鼠血浆EMP表达,改善肾脏皮质微循环,减轻肾损伤。“,”Objective:To clarify the characteristics of renal cortical microcirculation and its relationship with the expression of plasma endothelial microparticle (EMP) in septic rats, and to evaluate the effect of Xuebijing injection as an adjuvant therapy of antibiotics on septic AKI.Methods:The 8-10 weeks old specific pathogen free (SPF) male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), positive drug control group and Xuebijing group by the random number table method, with 10 rats in each group. The cecal ligation and puncture (CLP) with large ligation (ligated 75% of the cecum) was used to prepare a rat high-grade sepsis model; in the Sham group, the cecum was stretched without ligation or puncture. Due to the high mortality of CLP with large ligation, Xuebijing injection (4 mL/kg, 12 hours per time) and imipenem/cilastatin injection (90 mg/kg, 6 hours per time) were administered to the rats in the Xuebijing group via the tail vein immediately after the model was produced. Normal saline and imipenem/cilastatin were administered to the rats by the same methods in the positive drug control group. The rats in the Sham group were treated with the same volume of normal saline as any of the other two groups at the same frequency. At 48 hours after model reproduction, the mean arterial pressure (MAP) and blood lactic acid (Lac) of the rats were measured. The renal cortical microcirculation was monitored by using side stream dark-field imaging. Renal hypoxia signals were assessed by pimonidazole chloride immunohistochemistry. Plasma EMP levels were determined by using flow cytometry, and then the correlation between EMP and microcirculation parameters of renal cortex was analyzed. At the same time, the serum creatinine (SCr) was measured, and the renal injury score (Paller score) was used to evaluate the severity of renal tissue pathological damage.Results:Compared with the Sham group, perfused vessel density (PVD), microvascular flow index (MFI) and MAP in the positive drug control group and the Xuebijing group decreased significantly, the positive expression of hypoxia probe (pimonidazole) increased, Lac, EMP, Paller score and SCr increased significantly. However, compared with the positive drug control group, the renal cortical microcirculation in the Xuebijing group was improved significantly, PVD and MFI were increased significantly [PVD (mm/mmn 2): 16.20±1.20 vs. 9.77±1.12, MFI: 2.46±0.05 vs. 1.85±0.15, both n P < 0.05], Lac was reduced significantly (mmol/L: 4.81±1.23 vs. 6.08±1.09, n P 0.05], suggested that Xuebijing injection improved renal microcirculation perfusion in septic rats, and this effect did not depend on the change of MAP. The positive expression of pemonidazole in renal cortex of the Xuebijing group was significantly lower than that of the positive drug control group [(35.89±1.13)% vs. (44.93±1.37) %, n P < 0.05], suggested that Xuebijing injection alleviated renal hypoxia. The plasma EMP levels of rats in the Xuebijing group were significantly lower than those in the positive drug control group (×10 n 6/L: 3.49±0.17 vs. 5.78±0.22, n P < 0.05), and the EMP levels were significantly negatively correlated with PVD and MFI ( n r values were -0.94 and -0.95, respectively, both n P < 0.05), indicated that the increase of plasma EMP was highly correlated with renal microcirculation disorder, and Xuebijing injection inhibited the increase of plasma EMP levels. The Paller score in the Xuebijing group was significantly lower than that in the positive drug control group (46.90±3.84 vs. 62.70±3.05, n P < 0.05), and the level of SCr was also significantly lower than that in the positive drug control group (μmol/L: 121.1±12.4 vs. 192.7±23.9, n P < 0.05), which suggested that Xuebijing injection relieved kidney injury and improved renal function in septic rats.n Conclusion:As an adjuvant therapy of antibiotics, Xuebijing injection could inhibit the expression of plasma EMP in rats with sepsis, improve renal cortex microcirculation, and reduce kidney injury.
其他文献
目的:采用Meta分析方法评价下肢部位神经肌肉电刺激(NMES)对重症监护病房(ICU)机械通气患者的有效性。方法:应用计算机检索Cochrane图书馆数据库、美国国立医学图书馆PubMed数据库、科学网(Web of Science)、荷兰医学文摘Embase数据库、中国生物医学文献服务系统(SinoMed)、中国知网(CNKI)、维普中文科技期刊数据库(VIP)和万方数据中,从建库至2021年5月公开发表的有关ICU机械通气患者下肢部位进行NMES效果的随机对照试验(RCT)。对照组实施常规康复措施;
机械通气是急性呼吸窘迫综合征(ARDS)患者重要的支持治疗手段,但机械通气在提供有效呼吸支持时,若应用不当可导致肺部受到“二次打击”,引起呼吸机相关性肺损伤(VILI),使肺内炎性介质入血,引发或加重全身炎症反应综合征,甚至导致全身多器官功能衰竭。虽然保护性机械通气策略起到了重要的支持治疗作用,但ARDS机械通气患者病死率仍然很高。因此,肺保护性通气策略始终是ARDS的主要研究方向,具有重要的临床意义。本文通过对辅助和非辅助自主呼吸在ARDS机械通气患者中的应用及利弊进行综述,为研究和开发ARDS保护性通
目的:对比病原菌培养阳性脓毒症(CPS)与培养阴性脓毒症(CNS)患者的特征和结局,以了解培养阴性对预后的影响,并探讨其可能的死亡风险因素。方法:采用回顾性队列研究方法,以从美国重症监护医学信息数据库Ⅳv0.4(MIMIC-Ⅳv0.4)中筛选出的脓毒症患者作为研究对象。根据确诊脓毒症前后24 h内病原菌培养结果将患者分为CPS组和CNS组,比较两组患者的一般资料、病情资料及医疗操作等。在3个回归模型下,应用Logistic回归法分析CNS与住院病死率的关系。利用卡方分析及中介效应分析探讨初始抗菌药物治疗和
目的:探讨Toll样受体4(TLR4)通路在脓毒症大鼠心肌损伤和心功能障碍中的作用。方法:将18只雄性SD大鼠按照随机数字表法分为对照组、脂多糖(LPS)组和TLR4特异性抑制剂TAK242预处理组(TAK242+LPS组),每组6只。通过腹腔注射LPS 15 mg/kg诱导脓毒性心脏功能障碍大鼠模型;对照组给予等量生理盐水。TAK242+LPS组在给予LPS刺激前3 h腹腔注射3 mg/kg TAK242〔以0.2 g/L溶于10%二甲基亚砜(DMSO)+90%玉米油中〕;对照组和LPS组给予等量10%
目的:探讨微小RNA-1(miR-1)对缺氧/复氧(H/R)心肌细胞凋亡的调节作用。方法:体外培养大鼠胚胎心脏组织来源心肌细胞株H9c2,将处于对数生长期的细胞分为空白对照组、H/R组、miR-1模拟物(mimics)+H/R组、miR-1抑制剂反义寡核苷酸(ASO)+H/R组和微小RNA阴性对照片段(miRNA NC)+H/R组。用含低浓度胎牛血清(FBS)的低糖DMEM培养基作为缺氧条件下的培养基,置于37 ℃密闭无氧培养箱中(95% Nn 2和5% COn 2)培养12 h后,再
目的:比较右美托咪定(DEX)与咪达唑仑对脓毒性休克患者内源性血浆儿茶酚胺水平以及维持血压的外源性去甲肾上腺素(NE)用量的影响。方法:纳入2018年1月至2019年12月贵州医科大学附属医院重症医学科收治的需要有创机械通气且重症监护病房(ICU)住院时间≥48 h的接受DEX或咪达唑仑镇静的脓毒性休克患者。动态记录患者入ICU 0、12、24、48、72 h血流动力学数据、动脉血乳酸(Lac)水平、动脉血气分析及血管活性药物用量;记录入ICU 0、24、48 h血浆儿茶酚胺水平,入ICU时急性生理学与慢
目的:使用网状Meta分析方法评估序贯器官衰竭评分(SOFA)、快速序贯器官衰竭评分(qSOFA)及全身炎症反应综合征(SIRS)评分对感染或可疑感染患者死亡风险的预测价值。方法:应用计算机检索万方、中国知网(CNKI)、维普、美国国立医学图书馆PubMed、科学网(Web of Science)等中英文数据库,检索时间从2016年2月23日至2020年9月5日,同时追踪已检出文献的参考文献,收集关于比较SOFA、qSOFA与SIRS评分中2种或以上评分对感染或可疑感染患者死亡风险预测价值的队列研究。由2
目的:探讨血必净注射液(血必净)及其组分羟基红花黄色素A对脓毒症大鼠凝血功能和生存率的影响。方法:①凝血功能评估实验:将144只雄性SD大鼠按随机数字表法分为假伤组、盲肠结扎穿孔术(CLP)致脓毒症模型组(CLP组)、CLP+血必净组及CLP+羟基红花黄色素A组,每组36只。采用CLP制备脓毒症大鼠模型;假伤组大鼠仅开腹暴露盲肠后还纳腹腔,其余步骤同CLP组;CLP+血必净组及CLP+羟基红花黄色素A组大鼠术后经尾静脉注射血必净(4 mL/kg、每日2次)或羟基红花黄色素A溶液(0.378 g/L,每次2
目的:探讨长期口服β受体阻滞剂对脓毒症患者心肌损伤及预后的影响。方法:采用回顾性研究方法,选择浙江省立同德医院急诊重症监护病房(EICU)和重症监护病房(ICU)2015年1月至2020年6月收治的患者,将符合脓毒性心肌损伤诊断的289例患者纳入分析,其中确诊前3个月内未服用过β受体阻滞剂的187例患者为非β-blocker组,确诊前每日口服β受体阻滞剂≥3个月的102例患者为β-blocker组。比较两组患者确诊时心率、平均动脉压(MAP),确诊24 h内心肌肌钙蛋白I(cTnI)、脑钠肽(BNP)、肌
目的:探讨多时点急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)对重症脑卒中患者14 d死亡风险的影响,为临床诊疗提供参考。方法:收集美国重症监护医学信息数据库Ⅲ(MIMIC-Ⅲ)中3 229例重症脑卒中患者的相关信息。根据患者主要脑卒中类型分为蛛网膜下腔出血(SAH)、脑出血(ICH)、缺血性脑卒中(IS)及其他类型组;根据年龄分为>60岁和≤60岁组;根据序贯器官衰竭评分(SOFA)基线值分为>3分和≤3分组。计算患者APACHEⅡ评分的每日测量值,以患者入重症监护病房(ICU)14 d内全因死亡为结