1、 B1 45 SD , , 15 , 2 6 MV-X 20 Gy 48 h -1qd, 2 0.9%Na Cl 2 , - (HE) , , (qRT-PCR) (Western blot) B1 (HMGB1) (RAGE) kappa B (NF- - 6 (IL-6) 2 (COX-2) HE , , (3.42 (P0.05) HMGB1 RAGE NF- TNF- IL-6 COX-2 mRNA mRNA mRNA , HMGB1 , ( P0.05) HMGB1 ; B1; ; (1982-) , , , , , , , Tel: (0719) 8843185E-mail: (B
2、2016139) Prevention effects of ulinastatin on the early radiation-induced lung injury in rats by inhibiting high mobility group box 1 protein pathway TANG Ji-ying CAO Feng-jun WANG Xuan-bin CAI Xiao-jun LI Hong-liang LIU Ming CAO Yang XIANG Long-chao Affilicated to Hubei University of Medicine; Affi
3、licated to Hubei University of Medicine; Abstract Objective To observe the preventive and therapeutic effects of ulinastatin on early radiation-induced lung injury in rats and to explore its possible mechanism.Methods A total of 45 healthy female SD rats were randomly divided into normal group, mode
4、l group and experimental group, with 15 rats in each group.Radiation-induced lung injury model were established in the model group and the experimental group (whole-thorax irradiation utilizing 6 MV-X-ray, 20 Gy by X-ray) , while the normal group received no treatment.The experimental group were tre
5、ated with -1 qd) 48 h after irradiation, while the other two groups were given 0.9% Na Cl.After2 weeks, lung tissue was collected and HE staining was used to observe the morphology of lung tissue.The number of white blood cells and red blood cells in alveolar lavage fluid were calculated.The express
6、ion of high mobility group box-1 (HMGB1) , receptor for advanced glycation end-products (RAGE) , nuclear factor kappa B (NF- crosis factor alpha (TNF- (IL-6) and cyclooxygenase 2 (COX-2) were measured by qRT-PCR and Western blot.Results The degree of alveolitis in experimental group was significantl
7、y alleviated when compared with the model group.The number of white blood cells and red blood cells in the alveolar lavage fluid of of white blood cells and red blood cells in the alveolar lavage fluid of rats in the experimental group were also significantly lower than that in the model group (P 0.
8、05) .The expression of HMGB1, RAGE, NF- - -6 and COX- respectively.The expression of HMGB1 signaling pathway in the lung tissue of experimental group was significantly decreased when compared with the model group (P 0.05) .Conclusion Ulinastatin could alleviate the inflammatory changes of rat lung t
9、issue by regulating HMGB1 signaling pathway. Keyword ulinastatin; high mobility group box-1; radiation-induced lung injury; , , , 1 , 2 B1 (HMGB1) 3, HMGB1 1 SPF SD 45 , 180200 g, :SCXK ( ) 2014-0004 , : :031611044, (qRT-PCR) , Ta KaRa -Tubulin) HMGB1 (RAGE) kappa B (NF- - 6 (IL-6) 2 (COX-2) (HRP) ,
10、 Cell Signaling Technology 7300 , ABI ;Chemi DocXRS+ , Bio-Rad 2 4 SD 45 , , 15 10% , , , , SSD=100 cm, 6MV-X , 20 Gy , 48 h 10 d, 2 0.9%Na Cl 2 5 , , 4% , - (HE) ; , - 3 3.1 4 2 5 , , (PBS) 2 m L 3 , 5 min, PBS 3 PBS 4 m L 3.2 qRT-PCR HMGB1 mRNA 5 RNA, qRT-PCR HMGB1 GAPDH , 40 Ct 2 GAPDH, :5-AGGTCG
11、GTGTGAACG-GATTTG-3, :5-GGGGTCGTTGATG-GCAACA-3 HMGB1, :5-GCTGA-CAAGGCTCGTTATGAA-3, :5-CCTTT-GATTTTGGGGCGGTA-3 RAGE, :5-CTTGCTCTATGGGGAGCTGTA-3, :5-ATTGCCTGGCACCGGAAAA-3 NF- :5-ATGGCAGACGATGATCCCTAC-3, :5-CGGAATCGAAATCCCCTCTGTT-3 TNF- :5-CAGGCGGTGCCTATGTCTC-3, :5-CGATCACCCCGAAGTTCAGTAG-3 IL-6, :5-CTGC
12、AAGAGACTTC-CATCCAG-3, :5-AGTGGTATAGACAG-GTCTGTTGG-3 COX-2, :5-CACG-GACTTGCTCACTTTGTT-3, :5-GGAGAAGCGTTTGCGGTA-3 3.3 HMGB1 6 , , (SDS-PAGE) , , 10% 2 h, ( -Tubulin HMGB1 RAGE NF- TNF- IL-6 COX-2 , 000) 2 h, 4 SPSS 19.0 x , , LSD-t , Dunnetts T3 1 , , , , 2 , , 2 2 , (P0.05) , , 1 3 HMGB1 HMGB1 RAGE N
13、F- TNF- IL-6 COX-2 mRNA mRNA mRNA , HMGB1 mRNA (P0.05) , HMGB1 mRNA 4 HMGB1 , HMGB1 , HMGB1 , HMGB1 , , 1 1 1 Effect of ulinastatin on leukocyte and erythrocyte count in rat alveolar 1 B1 (HMGB1) Figure 1 Effect of ulinastatin on the expression of high mobility group box-1 (HMGB1) signaling pathway
14、protein in rat lung tissue HMGB1:High mobility group box 1;RAGE:Receptor for advanced glycation end-products;NF- - factor- -6:Interleukin-6;COX-2:Cyclooxygenase 2 , , , , 2 , 2 , 1 , HE , , HMGB1 , RAGE , NF- , TNF- IL-6 COX-2 , 7-8 , HMGB1 RAGE NF- TNF- IL-6 COX-2 , HMGB1 , 9 (EMT) , EMT 10-11 , HM
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18、017, 37 (1) :1-7. 8TOBON-VELASCO J C, CUEVAS E, TORRES-RAMOS M A.Receptor for AGEs (RAGE) as mediator of NF- inflammation and oxidative stressJ.CNS Neurol Disord Drug Targets, 2014, 13 (9) :1615-1626. 9DING N H, LI J J, SUN L Q.Molecular mechanisms and treatment of radiation-induced lung fibrosisJ.C
19、urr Drug Targets, 2013, 14 (11) :1347-1356. 10KIM J S, SON Y, JUNG M G, et al.Geranylgeranylacetone alleviates radiation-induced lung injury by inhibiting epithelialto-mesenchymal transition signalingJ.Mol Med Rep, 2016, 13 (6) :4666-4670. 11GAO F, SUN Z, SUN X, et al.Ulinastatin exerts synergistic effects with taxotere and inhibits invasion and metastasis of breast cancer by blocking angiogenesis and the epithelial-mesenchymal transitionJ.Cancer Biother Radiopharm, 2013, 28 (3) :218-225.
