穿心莲内酯对盲肠结扎穿孔诱导的脓毒症大鼠心肺功能和炎症损伤的保护作用  

Protective effects of andrographolide on cardiopulmonary function and inflammatory damage in sepsis rats induced by cecal ligation and perforation

作　　者：吴海涛[1] 周洪礼 宋玉[1] 石海霞[1] WU Haitao;ZHOU Hongli;SONG Yu;SHI Haixia(Department of Emergency Medicine,the Affiliated Hospital of Qinghai University,Xining 810001,China)

机构地区：[1]青海大学附属医院急诊内科,810001

出　　处：《天津医药》2022年第1期67-73,共7页Tianjin Medical Journal

基　　金：2019年青海省卫生健康系统指导性计划课题(2019-wjzdx-63)。

摘　　要：目的探究穿心莲内酯对盲肠结扎穿孔(CLP)诱导的脓毒症大鼠心肺功能和炎症损伤的保护作用。方法75只SD大鼠随机分为假手术组(A组)、脂多糖模型组(B组)、CLP组(C组)、CLP+低剂量穿心莲内酯组(D组)和CLP+高剂量穿心莲内酯组(E组),每组15只。A组仅进行开腹、分离盲肠及关腹手术;B组采用脂多糖腹腔注射建立脓毒症模型,C、D、E组行CLP手术诱导脓毒症,D、E组建模后分别腹腔注射10 mg/kg和20 mg/kg穿心莲内酯。比较各组大鼠心率(HR)、左心室射血分数(LVEF);采用酶联免疫吸附试验(ELISA)检测心肌肌钙蛋白I(c TnI)、肌酸激酶同工酶MB(CK-MB);比较各组大鼠肺损伤评分;采用血气分析仪检测氧分压[p(O2)],计算动脉血氧分压/吸入气氧浓度[PaO2/FiO2];取左肺组织计算湿/干质量(W/D)比值;HE染色观察心肺损伤情况;Western blot检测心肺组织中半胱氨酸天冬氨酸蛋白酶3(Caspase)-3、Caspase-9、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)和P65蛋白的表达;ELISA检测外周血中白细胞介素(IL)-6、肿瘤坏死因子(TNF-α)、IL-1β、中性粒细胞趋化因子1(CINC-1)水平;使用全自动血细胞分析仪检测中性粒细胞(NEU)水平。结果与A组相比,B、C组大鼠HR、LVEF、p(O2)和PaO2/FiO2均显著降低,cTnl、CK-MB、肺损伤评分、肺W/D比值、心肺组织中Caspase-3和Caspase-9蛋白表达、Bax/Bcl-2比值、CINC-1、NEU、IL-6、IL-1β、TNF-α和p-P65/P65水平均显著升高(P<0.05)。与C组相比,D、E组以上指标变化均相反(P<0.05);HE染色示,D、E组大鼠心肌肌纤维断裂溶解减少,肌细胞核溶解、固缩显著减少,肺间质中性粒细胞浸润减轻、肺泡间隔增厚、细胞水肿显著改善。结论穿心莲内酯可以缓解CLP诱导的脓毒症大鼠体内炎症反应并改善大鼠心肺功能,同时抑制凋亡蛋白的表达,保护大鼠心肺组织。Objective To explore the protective effects of andrographolide on cardiopulmonary function and inflammation damage in sepsis rats induced by cecal ligation and puncture(CLP).Methods A total of 75 SD rats were randomly divided into the sham operation group(group A),the lipopolysaccharide model group(group B),the CLP group(group C),the CLP+low-dose andrographolide group(group D) and the CLP+high-dose andrographolide group(group E),15 rats in each group.Rats in the group A only underwent laparotomy,cecum separation and abdominal closure surgery.In the group B,sepsis model was established by intraperitoneal injection of lipopolysaccharide.The group C,group D and group E were induced sepsis by CLP.Rats in the group D and group E were given intraperitoneal injection of 10 and 20 mg/kg andrographolide after modeling,respectively.The heart rate(HR) and left ventricular ejection fraction(LVEF) were compared between the five groups.The cardiac troponin I(cTnI) and creatine kinase MB(CK-MB) were detected by enzyme linked immunosorbent assay(ELISA).The scores of lung injury were compared between the five groups.The oxygen partial pressure p(02) was detected by blood gas analyzer.The partial pressure of arterial blood oxygen/fraction of inspired oxygen[PaO_(2)/FiO_(2)] was calculated.The left lung tissues were collected to calculate wet/dry weight ratio(W/D).The cardiopulmonary damage was observed by HE staining.The expression levels of cysteine proteinase-3(Caspase-3),cysteine proteinase-9(Caspase-9),Bcl-2 associated X protein(Bax),B-cell lymphoma-2(Bcl-2) and P65 in cardiopulmonary tissues were detected by Western blot assay.The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β) and cytokine-induced neutrophil chemoattractant-1(CINC-1) in peripheral blood were detected by ELISA.The level of neutrophils(NEU) was detected by full-automatic blood cell analyzer.Results Compared with the group A,values of HR,LVEF,p(O_(2))and PaO_(2)/FiO_(2) were significantly decreased in the group B and the g

关 键 词：脓毒症 穿心莲内酯 细胞凋亡 盲肠结扎穿孔 炎症 

分 类 号：R515.3[医药卫生—内科学]