盐酸戊乙奎醚对脓毒症大鼠肺组织高迁移率族蛋白B1 mRNA表达的影响

Effect of penehyclidine hydrochloride on the expression of high mobility group box 1 mrna in the lung tissue in septic rats

目的探讨盐酸戊乙奎醚对脓毒症大鼠肺组织高迁移率族蛋白B1（HMGBl）mRNA表达的影响。方法雄性Wistar大鼠30只，体质量200～250g，采用随机数字表法，将其随机分为3组（n=10）：假手术组（S组）、脓毒症组（L组）、盐酸戊乙奎醚组（PH组）。除S组外，其他2组采用盲肠结扎穿孔术制备大鼠脓毒症诱发急性肺损伤模型。PH组于术毕腹腔注射盐酸戊乙奎醚0．45mg／kg，S组和L组给予等容量生理盐水。分别于术后24、48h时处死5只大鼠，取肺组织，测定HMGBlmRNA表达、髓过氧化物酶（MPO）活性和核因子κB（NF-κB）活性，光镜下观察肺组织病理学结果。结果与s组比较，其他2组肺组织HMGB1 mRNA表达上调，MPO活性升高（P〈0．05）；与L组比较，PH组肺组织HMGBlmRNA表达下调，MPO活性降低（P〈0．01）。PH组肺组织NFxB活性逐渐降低，肺组织损伤程度逐渐减轻。结论盐酸戊乙奎醚减轻脓毒症大鼠急性肺损伤的机制与下调肺组织HMGBl基因表达有关，其下调HMGBl基因表达的机制与抑制NF-κB活化有关。

Objective To investigate the effect of penehyclidine hydrochloride on expression of high mobility group box 1 （HMGB1） mRNA in lung tissue in septic rats. Methods Thirty male Wistar rats weighing 200 250 g were randomly divided into 3 groups （ n = 10 each） ：group sham operation （group S）, group sepsis（group L）, group penehyclidine hydrochloride （groups PH）. Sepsis was induced by cecal ligation and puncture in groups L, PH. Penehyclidine Hydrochloride 0.45 mg/kg were injected intraperitoneally at the end of operation in groups PH. Five animals in each group were sacrificed at 24 and 48 h after operation respectively. The lungs were removed for microscopic examination and determination of HMGB1 mRNA expression, MPO activity and activation of NF-κB. Results Sepsis up-regulated HMGB1 mRNA and increased MPO activity and activation of NF-κB and induced lung histopathological damage. Penehyclidine Hydrochloride attenuated the above mentioned sepsis-induced changes in a dose- dependent manner. Conclusions Penehyclidine Hydrochloride can attenuate sepsis-induced acute lung injury by down regulating HMGB1 mRNA expression and inhibiting activation of NF-κB.