摘要
【目的】观察安宫牛黄丸对盲肠结扎穿孔术致脓毒症模型大鼠肺组织高迁移率族蛋白B1(HMGB1)mRNA表达及髓过氧化物酶(MPO)活性的影响。【方法】75只雄性SD大鼠随机分为正常对照组,脓毒症模型组(CLP组),1α-氰基-(3,4-羟基)N-苄苯乙烯胺组[AG490组,术前0.5 h皮下注射8 mg/kg的Janusk激酶2(JAK2)抑制剂AG490],雷帕霉素(RPM)组[RPM组,术前0.5 h皮下注射0.4 mg/kg的信号转导和转录激活子(STAT)抑制剂RPM],安宫牛黄丸低、中、高剂量组(术前0.5 h和术后6 h按1.0、2.0、3.0 g/kg剂量灌胃)。于造模后24 h活杀动物,留取肺组织,采用逆转录—聚合酶链反应(RT-PCR)法检测肺组织HMGB1 mRNA表达水平,同时测定MPO活性。【结果】与正常对照组比较,CLP组肺组织HMGB1 mRNA表达显著增强(P<0.01),MPO活性显著增高(P<0.05)。与CLP组比较,AG490组、RPM组以及安宫牛黄丸低、中、高剂量组HMGB1 mRNA表达显著下调(P<0.01),AG490组、RPM组以及安宫牛黄丸低、中剂量组MPO活性显著降低(P<0.05或P<0.01)。【结论】安宫牛黄丸治疗脓毒症的作用与AG490、RPM等JAK/STAT信号通路抑制剂相似,可下调肺组织HMGB1基因表达,降低肺组织MPO活性,减轻腹腔感染所致的急性肺损伤。
Objective To investigate the effect of Angong Niuhuang Bolus （ ANB ） on mRNA expression of high mobility group box-1 （ HMGB1 ） protein and myeloperoxidase activity in the lung of rats with sepsis induced by cecal ligation and puncture （CLP） method. Methods Seventy-five male SD rats were randomly divided into normal control group, model group, AG490 （a Janusk kinase inhibitor） treatment group （subcutaneous injection of AG490 8mg/kg 0. 5 h before CLP ）, rapamycin （RPM, a signal transduction and transcription activator inhibitor） treatment group （ subcutaneous injection of RPM 0.4 mg/kg 0. 5 h before CLP）, and low-, middle- and high-dose ANB groups （gastric gavage of ANB in the dose of 1.0, 2.0 and 3.0 g · kg^-1· d^-1 respectively）. The animals were sacrificed 24h after CLP, and then lung tissue samples were collected to determine the expression of HMGB1 mRNA by the method of reverse transcription polymerase chain reaction （RT-PCR）. Meanwhile, the activity of pulmonary myeloperoxidase （MPO） was also measured. Results Compared with the normal control group, the mRNA expression of HMGB1 was significantly enhanced （P 〈 0. 01 ） and pulmonary MPO activity was markedly increased （P 〈 0. 05） in the model group. Compared with the model group, HMGB1 mRNA expression was significantly down-regulated in AG490 group, RPM group, and low-, middle- and high-dose ANB groups （P 〈 0. 01 ） , and pulmonary MPO activity was decreased in AG490 group, RPM group, and low- and middle-dose ANB groups （P 〈 0. 05 or P 〈 0. 01 ）. Conclusion ANB can down-regulate pulmonary HMGB1 mRNA expression, decrease pulmonary MPO activity, and reduce acute lung injury induced by abdominal infection, which has an effect similar to AG490 and RPM for the treatment of sepsis in rats.
出处
《广州中医药大学学报》
CAS
2010年第1期27-30,共4页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(编号:30572453)
