摘要
目的探讨卡络磺钠对脓毒症大鼠急性肺损伤(ALI)的作用及机制。方法125只雄性Wistar大鼠随机分为假手术组、脓毒症组及卡络磺钠低剂量组(8 mg/kg)、中剂量组(40 mg/kg)、高剂量组(80 mg/kg),每组25只。另取大鼠20只,随机分为自噬抑制剂组(3-MA组)与卡络磺钠中剂量(40 mg/kg)组,每组10只。采用盲肠结扎穿孔法建立脓毒症模型后,腹腔注射不同剂量的卡络磺钠或3-MA。绘制大鼠生存曲线;术后24 h行肺部Micro-CT检查;行动脉血气分析;测量大鼠肺系数及肺血管通透性;HE染色观察肺组织病理变化并进行评分;Western blotting测定大鼠肺组织中LC3-Ⅱ/LC3-Ⅰ比值。结果与脓毒症组比较,各卡络磺钠组大鼠的生存率升高,动脉血氧分压及氧合指数增加,肺系数及肺血管通透性下降,差异有统计学意义(P<0.05)。肺影像学及肺组织HE染色显示,与脓毒症组比较,各卡络磺钠组大鼠肺组织病变及损伤程度减轻(P<0.05)。Western blotting检测结果显示,与假手术组比较,脓毒症组大鼠肺组织LC3-Ⅱ/LC3-Ⅰ比值明显升高(5.1±2.7 vs.2.7±0.7,P<0.05);与脓毒症组比较,卡络磺钠低、中剂量组大鼠肺组织LC3-Ⅱ/LC3-Ⅰ比值明显升高(6.8±2.6、8.9±1.4 vs.5.1±2.7),差异有统计学意义(P<0.05)。与卡络磺钠中剂量组比较,3-MA组大鼠肺组织LC3-Ⅱ/LC3-Ⅰ比值明显降低(3.1±1.7 vs.8.7±1.6),差异有统计学意义(P<0.05)。结论卡络磺钠能减轻脓毒症大鼠肺损伤,其机制与其上调肺组织自噬水平有关。
Objective To explore the effect and mechanism of carbazochrome sodium sulfonate on acute lung injury in septic rats.Methods Healthy male Wistar rats were randomized into 5 groups:sham group(n=25),sepsis group(n=25),low dose group(carbazochrome sodium sulfonate:8 mg/kg)(n=25),middle dose group(carbazochrome sodium sulfonate:40 mg/kg)(n=25),and high dose group(carbazochrome sodium sulfonate:80 mg/kg)(n=25).Two additional groups,the autophagy inhibition group(3-MA)(n=10)and the sepsis middle dose group(carbazochrome sodium sulfonate:40 mg/kg)(n=10),are also included in this study.After the preparation of septic rats by cecal ligation and puncture,the different doses of carbazochrome sodium sulfonate or 3-MA were given by intraperitoneal injection.The survival curve is drawn.After CLP 24 hours,the lung Micro-CT of those survival rats were examined.The arterial blood gas,pulmonary index and vascular permeability of lung tissue were measured.Pathological changes of lung tissues were observed by HE staining.The level of autophagic marker(LC3-Ⅱ/LC3-Ⅰ)of lung tissue was measured by Western blotting.Results Compared with sepsis group,the survival rate of the rats of carbazochrome sodium sulfonate groups increased,the arterial blood oxygen partial pressure and oxygenation index increased,the pulmonary index and vascular permeability decreased,and the differences were statistically significant(P<0.05).Both lung Micro-CT and HE staining showed that the lung lesions were more serious in sepsis group,while carbazochrome sodium sulfonate alleviated these lesions.Western blotting results showed that,the ratio of LC3-Ⅱ/LC3-Ⅰin lung tissue of septic rats was higher than sham group(5.1±2.7 vs.2.7±0.7,P<0.05),while the ratio of LC3-Ⅱ/LC3-Ⅰin lung tissue in the low dose and middle dose carbazochrome sodium sulfonate groups was further increased than sepsis group(6.8±2.6,8.9±1.4 vs.5.1±2.7,both P<0.05).The value of LC3-Ⅱ/LC3-Ⅰin the lung tissue of rats in 3-MA group was significantly lower than that in the middle d
作者
王娇
张秀珑
王佳兴
付鹤鹏
张玉想
Wang Jiao;Zhang Xiu-Long;Wang Jia-Xing;Fu He-Peng;Zhang Yu-Xiang(Graduate School of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Respiratory Medicine,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Critical Care Medicine,the Eighth Medical Center of Chinese PLA General Hospital,Beijing 100091,China;Department of Critical Care Medicine,Cangzhou Hospital of Integrated TCM-WM,Cangzhou,Hebei 061001,China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2021年第6期550-556,共7页
Medical Journal of Chinese People's Liberation Army
基金
军事医学创新工程(18CXZ023)
解放军总医院第八医学中心院内重点课题(2016ZD-008)。
关键词
脓毒症
急性肺损伤
卡络磺钠
自噬
sepsis
acute lung injury
carbazochrome sodium sulfonate
autophagy
