title: Xuebijing exerts protective effects on lung permeability leakage and lung injury by upregulating Toll-interacting protein expression in rats with sepsis.
abstract: Xuebijing (XBJ) is a type of traditional Tibetan medicine, and previous pharmacological studies have shown that the ethanol extract is derived from Chuanxiong, Chishao, Danshen and Honghua. Chuanxiong, Chishao, Danshen and Honghua possesses potent anti-inflammatory activity, and has been used in the treatment of inflammatory infectious diseases. In the present study, we investigated the effects of XBJ on pulmonary permeability and lung injury in cecal ligation and puncture (CLP)-induced sepsis in rats. A CLP sepsis model was established for the control and treatment groups, respectively. Approximately 2 h prior to surgery, an amount of 100 mg/kg XBJ injection was administered to the treatment group. Reverse transcription polymerase chain reaction (PT-PCR) and western blot analysis were used to examine the expression of Toll-interacting protein (Tollip), interleukin-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), nuclear factor-κB65 (NF-κB65) and TNF receptor-associated factor 6 (TRAF6) in lung tissue. ELISA was applied to detect changes of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-4 (IL-4) and interleukin-10 (IL-10) levels in bronchoalveolar lavage (BAL) fluid, and intercellular adhesion molecule 1 (ICAM-1) and von wille-brand factor (vWF) in serum. The number of neutrophils, albumin and total cells in the BAL fluid were measured. For histological analysis, hematoxylin and eosin (H&E) stains were evaluated. Lung permeability, the wet/dry weight ratio (W/D) and the lung pathology score were determined following the induction of ALI by CLP for 24 h. The results demonstrated that XBJ upregulated Tollip expression and blocked the activity of IRAK1, TLR4, NF-κβ65 and TRAF6. Additionally, the number of neutrophils and total cells were significantly decreased in the XBJ group compared to that in the control group. Lung permeability, the wet/dry weight ratio (W/D) and the lung pathology score were significantly decreased in the XBJ group. The histological results also demonstrated the attenuation effect of XBJ on CLP-induced lung inflammation. The results of the present study indicated that XBJ has a significantly reduced CLP-induced lung permeability by upregulating Tollip expression. The protective effects of XBJ suggest its therapeutic potential in CLP-induced acute lung injury treatment.
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Liu
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
authors.forename: Chuan-Yun
authors.initials: CY
authors.lastname: Qian
authors.affiliation: Surgical Intensive Care Unit, The Second Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000009:adverse effects; D008517:Phytotherapy; D011677:Punctures / Q000009:adverse effects; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000209:etiology / Q000517:prevention & control*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D048029:TNF Receptor-Associated Factor 6; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C549376:Xuebijing; C013090:ligatin; C539480:tollip protein, rat; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases