title: [Influences and mechanisms of somatostatin on inflammation in endotoxin-induced acute lung injury mice].
abstract: OBJECTIVE
  To investigate the effects of somatostatin on inflammation in endotoxin-induced acute lung injury mice and its underlying mechanisms.
  
  
  METHODS
  72 ICR male mice of specific pathogen free (SPF) were randomly divided into four groups: control group, SST control group, model group and SST intervention group, each group included 18 mice. The ALI model was reproduced by intraperitoneal injection of 40 mL/kg endotoxin, and the mice in control group was given intraperitoneal injection of equivalent normal saline. The mice in SST intervention group was given the subcutaneous injection of SST (20 μg, 20 mL/kg) at 0.5, 2, 6 and 12 hours after model reproduction. Six mice were sacrificed at 3, 8 and 16 hours after the first injection of LPS or NS. The lung wet/dry ratio (W/D) was calculated with oven drying method. Pathological changes in lung tissues were observed by light microscope. Serum SST, tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-10) levels were determined by enzyme linked immunosorbent assay (ELISA). The mRNA and protein expressions of Toll like receptor 4 (TLR4) and nuclear factor-ΚBp65 (NF-ΚBp65) were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.
  
  
  RESULTS
  There were no significant differences in above indexes between control group and SST control group. Compared with control group, lung W/D ratio, serum SST, TNF-α, IL-6, IL-10, and the mRNA and protein expressions of TLR4 and NF-ΚBp65 in model group were significantly increased. The W/D ratio, IL-6, IL-10, and the mRNA and protein expressions of TLR4 all peaked at 16 hours (W/D ratio: 6.32±0.18 vs. 4.14±0.14, IL-6: 673.78±56.13 ng/L vs. 50.17±7.06 ng/L, IL-10: 481.13±40.78 ng/L vs. 61.71±10.05 ng/L, TLR4 mRNA: 0.740±0.099 vs. 0.180±0.028, TLR4 protein: 0.935±0.067 vs. 0.222±0.019, all P<0.05), and SST, TNF-α, the mRNA and protein expressions of NF-ΚBp65 peaked at 8 hours (SST: 254.97±38.75 ng/L vs. 95.87±13.95 ng/L, TNF-α: 139.69±19.06 ng/L vs. 21.90±4.52 ng/L, NF-ΚBp65 mRNA: 0.753±0.065 vs. 0.190±0.026, NF-ΚBp65 protein: 1.214±0.079 vs. 0.303±0.067, all P<0.05). Compared with model group, the lung injury in SST intervention group was significantly improved, and the indexes were significantly decreased except for serum SST which was gradually increased (16-hour W/D ratio: 5.21±0.14 vs. 6.32±0.18, 8-hour TNF-α: 80.48±8.52 ng/L vs. 139.69±19.06 ng/L, 16-hour IL-6: 394.99±37.17 ng/L vs. 673.78±56.13 ng/L, 16-h IL-10: 326.95±36.41 ng/L vs. 481.13±40.78 ng/L, 16-hour TLR4 mRNA: 0.240±0.028 vs. 0.740±0.099, 16-hour TLR4 protein: 0.618±0.066 vs. 0.935±0.067, 8-hour NF-ΚBp65 mRNA: 0.240±0.045 vs. 0.753±0.065, 8-hour NF-ΚBp65 protein: 0.784±0.041 vs. 1.214±0.079, all P<0.05).
  
  
  CONCLUSIONS
  SST has significant protective effects on endotoxin-induced ALI via direct suppression of the TLR4-NF-ΚB cytokine pathway, thus alleviate lung tissue inflammation.
authors.affiliation: Department of Emergency, the First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, Zhejiang, China. Corresponding author: Lu Zhongqiu, Email: lzq640815@163.com.
authors.forename: Liyan
authors.initials: L
authors.lastname: Xu
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenwen
authors.initials: W
authors.lastname: Han
authors.forename: Chao
authors.initials: C
authors.lastname: Nan
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Guangliang
authors.initials: G
authors.lastname: Hong
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhao
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004731:Endotoxins / Q000009:adverse effects; D007249:Inflammation / Q000188:drug therapy*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000235:genetics; D013004:Somatostatin / Q000494:pharmacology* / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; C556062:IL10 protein, mouse; D015850:Interleukin-6; D012333:RNA, Messenger; C498144:Rela protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013004:Somatostatin