摘要
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/mm^(2)):16.20±1.20比9.77±1.12,MFI:2.46±0.05比1.85±0.15,均P<0.05〕,Lac水平明显降低(mmol/L:4.81±1.23比6.08±1.09,P<0.05),MAP略有升高〔mmHg(1 mmHg=0.133 kPa):84.00±2.00比80.00±2.00,P>0.05〕,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)%,P<0.05〕,提示血必净注射液能减�
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 pos
作者
刘景峰
王振洲
李甜
国新杰
庞冉
段美丽
Liu Jingfeng;Wang Zhenzhou;Li Tian;Guo Xinjie;Pang Ran;Duan Meili(Department of Critical Care Medicine,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2021年第10期1203-1208,共6页
Chinese Critical Care Medicine
基金
国家自然科学基金(81471849)。
关键词
脓毒症
急性肾损伤
微循环
血必净注射液
内皮微粒
Sepsis
Acute kidney injury
Microcirculation
Xuebijing injection
Endothelial microparticle
