ABSTRACT
Objective@#To investigate the interventional effects of BAY11-7082 on lung inflammatory response at the early stage and acute lung injury of rats with severe burns.@*Methods@#(1) Experiment 1. Twelve Sprague-Dawley (SD) rats were divided into control (C) group and burn (B) group according to the random number table, with 3 rats in group C and 9 rats in group B. Rats in group C did not receive any special treatment. Rats in group B were inflicted with 30% total body surface area full-thickness burn on the back. Immediately after injury, rats in group B were intraperitoneally injected with normal saline in the dosage of 50 mL/kg. Abdominal aorta blood and lung tissue samples were collected from three rats in group B at post injury hour (PIH) 12, 24, and 48, respectively. The interleukin-1β (IL-1β) and the IL-18 content of serum were determined with enzyme-linked immunosorbent assay. The mRNA expressions of IL-1β and IL-18 in lung tissue were determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR). Sample collection and determination in rats of group C were performed as above. (2) Experiment 2. Eighteen SD rats were divided into control (C) group, simple burn (SB) group, and BAY11-7082 intervention (BI) group according to the random number table, with 6 rats in each group. Rats in group C did not receive any special treatment. Rats in groups SB and BI were inflicted with injury as in experiment 1. Immediately after injury, rats in group SB were intraperitoneally injected with normal saline in the dosage of 50 mL/kg, and those in group BI with 8 mg/mL (final mass concentration) BAY11-7082 solution in the dosage of 50 mL/kg. Lung tissue and bronchoalveolar lavage fluid (BALF) of rats with burns were collected at the optimal observation time point concluded from experiment 1. The morphology of lung tissue was observed with hematoxylin-eosin staining, and the pathological damage of lung tissue was graded. The myeloperoxidase (MPO) content of lung tissue and the total protein content of BALF were detected by microplate reader. The protein expressions of nucleotide-binding oligomerization domain-like receptor-3 (NLRP3) and cysteine-aspartic proteases 1 (caspase-1) in lung tissue were determined with Western-blotting. The mRNA expressions of IL-1β, IL-18, NLRP3, and caspase-1 in lung tissue were determined with real-time fluorescence quantitative RT-PCR. Sample collection and determination in rats of group C were performed as above. Data were processed with one-way analysis of variance and LSD-t test.@*Results@#(1) The IL-1β and IL-18 content of serum in rats of group B at PIH 12, 24, and 48 were significantly higher than those of group C (t=10.55, 22.05, 12.47, 10.60, 15.22, 11.94, P<0.01). The mRNA expressions of IL-1β and IL-18 in rats of group B at PIH 12, 24, and 48 were significantly higher than those of group C (t=3.62, 7.19, 5.28, 3.20, 12.62, 7.31, P<0.05 or P<0.01). PIH 24 was the optimal observation time point for the following experiment. (2) At PIH 24, compared with those in group SB, the inflammatory cell infiltration and erythrocyte exudates of alveolar in group BI were obviously reduced, and the pulmonary interstitial edema obviously subsided. The pathological damage score of lung tissue in rats of group SB was (9.00±1.00) points, significantly higher than (1.10±0.26) points of group C (t=13.23, P<0.01). The pathological damage score of lung tissue in rats of group BI was (4.93±0.70) points, which was significantly lower than that of group SB (t=5.76, P<0.01) but still significantly higher than that of group C (t=8.84, P<0.01). At PIH 24, the MPO content of lung tissue and the total protein content of BALF in rats of group SB were (1.83±0.15) U/mg and (1.39±0.20) mg/mL, respectively, significantly higher than (0.51±0.10) U/mg and (0.44±0.05) mg/mL of group C (t=12.50, 7.86, P<0.01). The MPO content of lung tissue and the total protein content of BALF in rats of group BI were (0.91±0.12) U/mg and (0.60±0.10) mg/mL, respectively, significantly lower than those of group SB (t=8.36, 6.06, P<0.01). At PIH 24, the protein expressions of NLRP3 and caspase-1 in lung tissue of rats of group SB were 3.10±0.09 and 2.99±0.30, respectively, significantly higher than 1.00 and 1.00 of group C (t=9.06, 11.28, P<0.01). The protein expressions of NLRP3 and caspase-1 in lung tissue of rats of group BI were 1.13±0.08 and 1.81±0.11, respectively, significantly lower than those of group SB (t=7.24, 3.91, P<0.05 or P<0.01). At PIH 24, the mRNA expressions of IL-1β, IL-18, NLRP3, and caspase-1 in lung tissue of rats in group SB were 5.0±0.4, 3.32±0.21, 3.54±0.42, and 6.3±1.0, respectively, significantly higher than 1.0, 1.00, 1.00, and 1.0 of group C (t=13.97, 14.14, 11.78, 7.13, P<0.01). The mRNA expressions of IL-1β, IL-18, NLRP3, and caspase-1 in lung tissue of rats in group BI were 2.6±0.5, 2.00±0.28, 1.39±0.21, and 2.5±0.5, respectively, significantly lower than those of group SB (t=7.11, 5.80, 9.99, 4.65, P<0.05 or P<0.01).@*Conclusions@#Applying BAY11-7082 at the early stage of acute lung injury of rats with severe burn can reduce the expression of caspase-1, decrease the levels of IL-1β and IL-18, and decrease the MPO content of lung tissue and the total protein content of BALF through inhibiting NLRP3, thus alleviating the lung inflammatory response and lung injury.
ABSTRACT
OBJECTIVE: To explore the clinical effects of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine ( Fuchunsan ) on the treatment of postburn hyperplastic scar. METHODS: Sixty-three patients with hyperplastic scar after burn injury hospitalized from February 2012 to June 2014 in our department were treated with lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan). Patients were divided into early stage group (E, n = 35), middle stage group (M, n = 25), and late stage group ( L, n = 3) according to the formation time of scar, which was respectively 3 weeks to 3 months, longer than 3 months and less than or equal to 6 months, and 3 to 15 years in groups E, M, and L. The number of times of laser treatment of patients in each group was recorded. The degree of scar pain in patients of the three groups was assessed by the Numerical Rating Scale (NRS) before treatment and after treatment for 1, 2, and 3 times. The scar condition of patients in groups E and M was assessed by the Vancouver Scar Scale (VSS) before treatment and after treatment for 1, 3, and 5 times. Patients in group L did not receive VSS assessment but were evaluated by clinical observation only. Photos of scar in treating area were taken before treatment and after treatment for 3 and 5 times to evaluate the clinical effect. Data were processed with t test. RESULTS: Patients in groups E and M were treated with laser for (4.8 ± 1.1) and (7.7 ± 2.1) times respectively. In group L, the treatment was stopped in 2 patients after laser treatment for 5 times, and 1 patient received laser treatment for 12 times. The degree of pain in patients of groups E and M was alleviated significantly after treatment for one time, and the number of patients scoring 1-4 point(s) in NRS increased from 5 cases to 38 cases. After treatment for 2 and 3 times, the increase in the number of patients scoring 1-4 point (s) in NRS was on a small scale. Before treatment and after treatment for 1 time, VSS scores of patients in groups E and M were similar (with values respectively 0.641 and 0. 082, P values above 0. 05). After treatment for 3 and 5 times, VSS scores of patients in group E were respectively (9.2 ± 0.8) and (7.0 ± 1.1) points, which were significantly lower than those in group M [ (9.7 ± 1.0) and (8.2 ± 1.0) points, with values respectively -1.993 and -4.433 , P < 0.05 or P < 0.01]. After treatment for 3 times, the rate of improvement in appearance was respectively 88.6% (31/35) and 72.0% (18/25) in groups E and M, and it was respectively 100.0% (35/35) and 96.0% (24/25) after treatment for 5 times. No significant effect in appearance was found in the 3 patients in group L. CONCLUSIONS: Early application of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan) for the treatment of postburn hyperplastic scar is effective.
