Effect of Baicalin on chronic pulmonary infection of multidrug resistant Pseudomonas aeruginosa in rats
LI Lei1* WANG Jing2* CUI Lanfeng3* LYU Siyuan1 GUO Yufei1 QIN Xinxin1 WANG Chengxiang1
1.Department of Respiratory, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, China;
2.Office of Academic Affairs, Beijing University of Chinese Medicine, Beijing 100029;
3.Department of Traditional Chinese Medicine, Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University, Beijing 102218, China
Abstract：Objective To study the effect of Baicalin on chronic pulmonary infection of multidrug resistant Pseudomonas aeruginosa (MDRPA) in rats. Methods Thirty-two SPF male SD rats (6-8 weeks old, weight 180-220 g) were randomly divided into blank group, model group, western medicine group, and Baicalin group, with eight rats in each group. Among them, the model group, western medicine group, and the Baicalin group were injected with MDRPA alginate coated body through ortracheal intubation to establish the rat model of MDRPA chronic pulmonary infection. The Baicalin group was given 0.8 g/(kg·d) Baicalin by gavage, and the western medicine group was given 0.8 g/(kg·d) Piperacillin Tazobactam Sodium intramuscular injection. The blank group and the model group were given the same amount of normal saline as the Baicalin group by gavage. After 14 days of intervention, serum and lung tissues of the four groups were collected, and the lung tissues were observed by hematoxylin-eosin staining. The levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in serum were detected by enzyme-linked immunosorbent assay. The mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor κB (p65 subunit) (NF-κB p65) in lung tissue were detected by quantitative polymerase chain reaction. Results The lung tissue of blank group was normal. In the model group, a large number of inflammatory cells were infiltrated and the alveolar wall was significantly thickened. In Baicalin group, there were fewer inflammatory cells and thinner alveolar wall in lung tissues. The levels of serum TNF-α and the levels of TLR4 and NF-κB p65 mRNA in lung tissues in the model group were higher than those in the blank group, and the level of serum IL-10 was lower than that in the blank group (P ＜ 0.05). The levels of serum TNF-α and the levels of TLR4 and NF-κB p65 mRNA in lung tissues in Baicalin group were lower than those in model group, and the level of serum IL-10 was higher than that in model group (P ＜ 0.05). Conclusion Baicalin can reduce the inflammatory injury of lung tissues in rats with MDRPA chronic lung infection, and the mechanism may be related to the inhibition of TLR4/NF-κB pathway activation.
[1] Kalil A，Metersky M，Klompas M，et al. Management of adults with hospitalacquired and ventilator-associated pneumonia：2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society [J]. Clin Infect Dis，2016，63：e61-e111.
[2] Luyt C，Hekimian G，Koulenti D，et al. Microbial cause of ICU-acquired pneumonia：hospital-acquired pneumonia versus ventilator-associated pneumonia [J]. Curr Opin Crit Care，2018，24：332-338.
[3] Lin C，Kazmierczak B. Inflammation：A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection [J]. J Innate Immun，2017，9（3）：250-261.
[4] Hwang J，Wang C，Chou F. Protective effect of baicalin on tert-butyl hydroperoxide-induced rat hepatotoxicity [J]. Arch Toxicol，2005，79（2）：102-109.
[5] Peng L，Yuan M，Song K. Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-κB pathway activation [J]. Int Immunopharmacol，2019，72：467-472.
[6] Meers P，Neville M，Malinin V，et al. Biofilm penetration，triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections [J]. J Antimicrob Chemother，2008，61（4）：859-868.
[7] 徐淑云，卞如濂，陈修.药理实验方法学[M].3版.北京：人民卫生出版社，2002：202-203.
[8] Maurice N，Bedi B，Sadikot R. Pseudomonas aeruginosa Biofilms：Host Response and Clinical Implications in Lung Infections [J]. Am J Respir Cell Mol Biol，2018，58（4）：428-439.
[9] Mets O，Roothaan S，Bronsveld I，et al. Emphysema is common in lungs of cystic fibrosis lung transplantation patients：a histopathological and computed tomography study [J]. PLoS One，2015，10：e0128062-0128073.
[10] Perera P，Screaton N. Radiological features of bronchiectasis [J]. Eur Respir Mon，2011，52：44-67.
[11] Elborn S，Vallieres E. Cystic fibrosis gene mutations：evaluation and assessment of disease severity [J]. Adv Genomics Genet，2014，4：161-172.
[12] Perros F，Lambrecht B，Hammad H. TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways [J]. Respir Res，2011，12：125-133.
[13] Schoeniger A，Fuhrmann H，Schumann J. LPS- or Pseudomonas Aeruginosamediated activation of the macrophage TLR4 signaling cascade depends on membrane lipid composition [J]. PeerJ，2016，4：1663-1680.
[14] Wieland C，Lieshout M，Hoogendijk A，et al. Host defence during Klebsiella pneumonia relies on haematopoietic-expressed Toll-like receptors 4 and 2 [J]. Eur Respir J，2011，37（4）：848-857.
[15] Greenhill C，Rose J，Lissilaa R，et al. IL-6 trans-signaling modulates TLR4-dependent inflammatory responses via STAT3 [J]. J Immunol，2011，186（2）：1199-1208.
[16] Liu Y，Yin H，Zhao M，et al. TLR2 and TLR4 in autoimmune diseases：a comprehensive review [J]. Clin Rev Allergy Immunol 2014，47（2）：136-147
[17] Wang P，Li N，Li J，et al. The role of endotoxin，TNFalpha，and IL-6 in inducing the state of growth hormone insensitivity [J]. World J Gastroenterol，2002，8（3）：531-536.
[18] Kellum J，Kong L，Fink M，et al. Understanding the inflammatory cytokine response in pneumonia and sepsis：results of the Genetic and Inflammatory Markers of Sepsis（GenIMS）Study [J]. Arch Intern Med，2007，167（15）：1655-1663.
[19] Gilroy D，Maeyer R. New insights into the resolution of inflammation [J]. Semin Immunol，2015，27：161-168.
[20] Qiu J，Chi G，Wu Q，et al. Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NFκB signaling in a murine model [J]. Int Immunopharmacol，2016，31：109-115.
[21] Li Y，Wu R，Tian Y，et al. RAGE/NF-κB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model [J]. Int J Clin Exp Med，2015，8（8）：13371-13376.
[22] 刘凤，杨燕，田应彪，等.石榴皮提取物鞣质对耐药鲍氏不动杆菌超微结构变化的电镜观察[J].中华医院感染学杂志，2015，25（22）：5056-5059.
[23] Oliveira J，Jesus V，Martins A，et al. extract has antimicrobial and anti-inflammatory effects in the absence of cytotoxicity and genotoxicity [J]. Arch Oral Biol，2017，82（10）：271-279.
[24] 周芳芳，杨温仪，王蕾.黄连解毒汤对100株临床多重耐药菌的体外抑菌效果研究[J].国际检验医学杂志，2018，39（24）：3061-3065.
[25] 张颖颖，邵尉，王彦芳，等.黄芩、黄连水提物对常见临床耐药菌株的作用研究[J].食品与药品，2017，19（1）：42-46.
京公网安备 11010502046598号