CAJ | 학술논문

目的：探讨铜绿假单胞菌甘露糖敏感血凝素（PA-MSHA）对脓毒症致急性肺损伤的影响及可能机制。方法以盲肠结扎穿孔法（CLP）复制大鼠脓毒症模型。按随机数字法将120只健康SD大鼠分为假手术对照组（SC组）、脓毒症组（CLP组）、术前治疗组（PreT组）和术后治疗组（PosT组），每组各30只。于制模后12、24、36 h分别采集外周血测定血清肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-10及转化生长因子β（TGF-β）浓度并计算肺损伤病理评分。采用逆转录聚合酶链反应（RT-PCR）方法检测肺组织Toll样受体4（TLR4）mRNA表达，并作肺组织TLR4 mRNA表达与病理学评分的Pearson相关性分析。结果 SC组各时间点血清细胞因子浓度无明显变化（F＝0.04、0.09、1.25、1.77，P均>0.05）。与CLP组和PosT组相比，各时间点PreT组的血清TNF-α、IL-6浓度明显较低，而IL-10、TGF-β浓度明显较高（P均<0.05），而PosT组仅在术后36 h的IL-10高于CLP组（P<0.05）。四组大鼠间的肺组织TLR4 mRNA表达水平及四组间各时间点肺组织病理学评分比较，差异均有统计学意义（F＝66.01、20.03、71.21、69.02，P均<0.05）， SC组及PreT组明显优于CLP组和PosT组（P均<0.05）。同时，肺组织TLR4 mRNA表达与病理学评分存在明显的相关性（r＝0.732，P<0.05）。结论术前给予PA-MSHA可减轻脓毒症大鼠肺病理损伤，其机制可能与调节外周血单核细胞TLR4表达水平、调控细胞因子平衡、减轻炎症级联放大效应有关。
목적：탐토동록가단포균감로당민감혈응소（PA-MSHA）대농독증치급성폐손상적영향급가능궤제。방법이맹장결찰천공법（CLP）복제대서농독증모형。안수궤수자법장120지건강SD대서분위가수술대조조（SC조）、농독증조（CLP조）、술전치료조（PreT조）화술후치료조（PosT조），매조각30지。우제모후12、24、36 h분별채집외주혈측정혈청종류배사인자α（TNF-α）、백세포개소6（IL-6）、IL-10급전화생장인자β（TGF-β）농도병계산폐손상병리평분。채용역전록취합매련반응（RT-PCR）방법검측폐조직Toll양수체4（TLR4）mRNA표체，병작폐조직TLR4 mRNA표체여병이학평분적Pearson상관성분석。결과 SC조각시간점혈청세포인자농도무명현변화（F＝0.04、0.09、1.25、1.77，P균>0.05）。여CLP조화PosT조상비，각시간점PreT조적혈청TNF-α、IL-6농도명현교저，이IL-10、TGF-β농도명현교고（P균<0.05），이PosT조부재술후36 h적IL-10고우CLP조（P<0.05）。사조대서간적폐조직TLR4 mRNA표체수평급사조간각시간점폐조직병이학평분비교，차이균유통계학의의（F＝66.01、20.03、71.21、69.02，P균<0.05）， SC조급PreT조명현우우CLP조화PosT조（P균<0.05）。동시，폐조직TLR4 mRNA표체여병이학평분존재명현적상관성（r＝0.732，P<0.05）。결론술전급여PA-MSHA가감경농독증대서폐병리손상，기궤제가능여조절외주혈단핵세포TLR4표체수평、조공세포인자평형、감경염증급련방대효응유관。
Objective To investigate the effects and possible mechanism of pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on acute lung injury in septic rats. Methods Rats septic model was reproduced by cecal ligation puncture (CLP). Totally 120 healthy SD rats were randomly divided into the sham operation group (SC group), sepsis group (CLP group), PA-MSHA treatment before CLP (PreT group), PA-MSHA treatment after CLP (PosT group), 30 rats in each group. Rats in each group were sacrificed respectively at 12, 24, 36 h after operation, and serum tumor necrosis-α (TNF-α), interleukin-6 (IL-6), IL-10 and transforming growth factor-β (TGF-β) were examined. The lung tissue samples were collected to calculate the pulmonary pathological scores and determine the expression of TLR4 mRNA by reverse transcription-polymerase chain reaction. Pearsonˊs method was employed to analyze the correlation between the expression of TLR4 mRNA and the pulmonary pathological scores. Results There were no significant differences in the serum cytokine concentrations at each time point (F=0.04, 0.09, 1.25, 1.77; all P>0.05). In the PreT group, the levels of TNF-αand IL-6 were lower, IL-10 and TGF-β were higher at each time point than those in the CLP and PosT groups (all P<0.05), and IL-10 in the PosT group only at 36 h was higher than those in the CLP group (P < 0.05). The expressions of TLR4 mRNA and lung injury pathological score at each time point all showed significant differences among the four groups (F = 66.01, 20.03, 71.21, 69.02; all P<0.05), which were better in the SC and PreT groups than those in the CLP and PosT groups (all P < 0.05). Meanwhile, the expression of TLR4 mRNA was correlated with the pulmonary pathological scores (r = 0.732, P < 0.05). Conclusions The pathological injury in lung was milder when the septic rat was treated with PA-MSHA before CLP. The mechanism may be related to the adjusted levels of TLR4 expression in peripheral blood mononuclear cells, the regulated inflammatory cytokine balance and the reduced inflammation cascade effect.