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Objective To investigate the impact of AG490 on the blood-brain barrier (BBB ) permeability and the expression of interleukin-6 (IL-6 )and tumor necrosis factor-α(TNF-α)after traumatic brain injury (TBI)in rats. Methods A total of 144 healthy male SD rats were randomly divided into a control group,a trauma group,and an AG490 intervention group (n=48 in each group). The rats in each group were redivided into four subgroups (4 h,1 d,3 d,and 7 d subgroups)according to the time points after cerebral injury (n=12 in each subgroup). A brain trauma models were induced by hydraulic shock method. Evans blue was used to determine the changes of the BBB permeability after cerebral injury in each group. Real-time fluorescence quantitative PCR was to detect the expression levels of TNF-αand IL-6 mRNA in rat brain tissue. Immunohistochemistry was used to detect the expression of human phospho tyrosine kinase (P-JAK2). Results (1)The permeability of BBB:The permeability of BBB increased at 4 h,1 d,3 d and 7 d after brain injury in the trauma group (Evans blue permeation:10. 4 ± 1. 2,16. 0 ± 1. 4,22. 3 ± 2. 0,and 8. 4 ± 0. 9μg/g,respectively). Compared with the control group, there were significant differences (all P<0. 01). The Evans blue permeation of the AG490 intervention group were 9. 1 ± 1. 0,12. 8 ± 1. 1,17. 5 ± 1. 4 and 7. 1 ± 0. 8μg/g,respectively at each time point,and they were all significantly lower than those of the trauma group (all P<0. 01). (2)The expression of IL-6 and TNF-α mRNA:The expression levels of IL-6 mRNA and TNF-α mRNA at 4 h,1 d,3 d and 7 d after traumatic brain injury in the trauma group were 2. 31 ± 0. 35,2. 73 ± 0. 35,3. 32 ± 0. 29,2. 14 ± 0. 24 and 7. 46 ± 1. 18,9. 42 ± 1. 54,13. 76 ± 1. 89,and 6. 28 ± 1. 00,respectively,they were all significantly higher than those of the control group (all P<0. 01). The expression levels of IL-6 mRNA and TNF-α mRNA of the AG490 intervention group were 1. 14 ± 0. 22,1. 54 ± 0. 23,1. 94 ± 0. 32,1. 26 ± 0. 21 and 5. 57 ± 0. 88, 7. 78 ± 1. 02,11. 51 ± 1. 29,and 5. 05 ± 0. 97,respectively,they were all lower than those of the trauma group,but they still higher than the control group. There were significant differences (all P<0. 01). (3 )The expression of P-JAK2:The expression levels of P-JAK2-positive cells at each time point after traumatic brain injury in the trauma group were significantly higher than the control group (all P<0. 01),they were 17. 4 ± 2. 7,56. 2 ± 6. 7,26. 1 ± 5. 4,and 15. 3 ± 2. 5,respectively;those of the AG490 intervention group were 12. 2 ± 1. 4,41. 5 ± 4. 6,19. 4 ± 4. 1,and 9. 6 ± 2. 0,respectively,they were all lower than those of the trauma group,but still higher than the control group. There were significant differences (all P<0. 01). Conclusion During the acute phase after TBI,AG490 may activate the factor signaling pathways by inhibiting the non-receptor tyrosine kinase/signal transduction and transcription,significantly inhibit the expression of brain tissue inflammatory cytokines IL-6 IL-6 and TNF-α,reduce the BBB damage,and help to reduce secondary brain injury.
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Objective To evaluate the level of MMP-2 and COX-2 Protein in bladder transitional cell carcinoma tissue and explore their relationships. Methods A total of 42 patients with bladder transitional cell carcinoma, including Ta-T1 (n=18), T2-T4 (n=24), G1(n=12), G2 (n=19), G3 (n=11), metastasis (n=26) and without metastasis (n=16), were enrolled in the study. Eight normal bladder tissues were selected as control group. Western blotting was performed todetect the mRNA level of MMP-2 and COX-2. Results The relative COX-2 protein level of Ta-T1 (0.729±0.458), T2-T4 (1.248±0.425), G1 (0.61±0.486), G2 (1.055±0.406), G3 (1.422±0.341) were all higher than that of the control group significantly (0.31±0.149, t = 3.56, 4.13; F = 5.98, P ＜0.05). The relative MMP-2 protein level of Ta-T1 (0.844±0.345), T2-T4 (1.458±0.463), G1 (0.971 ±0.370), G2(1.445±0.378), G3 (1.755±0.387) were all higher than that of the control group (0.460±0.213, t = 3.91, 4.83;F = 6.35, P ＜0.05). The COX-2 and MMP-2 protein level in tumor tissues with and without metastasis were 1.246±0.426 vs 0.668±0.421, 1.430±0.461 vs 0.814±0.341, t = 5.89, 6.27, P ＜0.01, respectively. The level of COX-2 protein was positively correlated with MMP-2 positively (r =0.48, P ＜0.01). Conclusion MMP-2 and COX-2 protein are highly expressed in bladder transitional cell carcinoma tissue and their expression is positively correlated with the malignant degree. MMP-2 and COX-2 might play a synergetic role in the carcinogenesis of bladder transitional cell carcinoma.
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Objective To investigate the mRNA expression of COX-2 and MMP-2 on transitional cell carcinoma of bladder(TCCB) and their relationship with the invasion and metastasis of the bladder neoplasm. Methods Surgical bladder specimens were obtained from 54 TCCB patients and 5 benign prostate hyperplasia (BPH) patients to make paraffin slices, and 8 specimens which against cancers. In situ hybridization (ISH) was used to assay the mRNA expression of COX-2 and MMP-2. Results The mRNA expression of COX-2 and MMP-2 in bladder neoplasm were 59.2 % and 57.4 % respectively. Compared to the control, their expression was higher (P