The effects of Rheu compositus on alveolar macrophages NF-κB activity and inflammatory cytokine expres-sion in rats with ARDS / 中华急诊医学杂志

ABSTRACT

Objective Tostudy the effects ofRheu compositus (Dachengqi Decoction, DD) on the NF-κBactivity of alveolar macrophages in ARDS rats and its inflammatory cytokine expression, and hence to explore the molecular mechanism of the anti-inflammatory effects of DD. Method The 65 male Wistar rats were randomly di-vided into the control group (n = 12), the ARDS model group (n = 21), the DD treatment group (n = 16) and the dexamethasone treatment group (n = 16). The rots of model group received 1 mg/(kg·0.5 mL) LPS injected intra-poritoneally and LPS in dose of 5 mg/(kg·0. 5 mL) was administrated by slow dropping endotracbeally 16 hours later. Modeling was successfully established 6 hours later evidenced by arterial gas analysis. The rats of con-trol group received 0.5 mL normal saline injected intravenously through tail vein instead of LPS. Three days after establishment of modeling, DD was given to rats of DD treatment group by intragastric instillation for 3 days in dose of 2.31 g/(kg·d),in which the weight of drug was calculated on the basis of dried herbal medicine. In dexam-ethasone treatment group, rats had intra-peritoneal injection of 2 mg/kg dexamethasone for 3 days after modeling was established. Seventy-two hours later, the arterial blood gas analysis and pathological study were carried out, in rats of all groups, and the findings were graded. The levels of TNF-α, IL-1 and IL-10 both in the plasma and in the brenchoalveolar lavage fluid were determined by using the enzyme linked immunosorbent assay (ELISA). Besides the nucleopretein concentration of pulmonary alveolar macrophage (PAM) was maeasuredwith the BAC method, and the NF-κB activity was determined with the Western Blotting, and with the evaluation of the DD' s effect on the transcription activity of PAM inflammatory cytokines. All the experimental data were processed by the SPSS 13.0 for statistical analysis. The analysis of variance was used for the comparison between groups, and P < 0. 05 showed the statistical significance of the difference. Results DD didn' t significantly reduce the TNF-α level [(510.97±76.20) pg/mL,(476.16±98.03) pg/mL, P >0.05], but significantly deceased the plasma IL-1 level [(381.99±34.30) pg/mL, (300.69 ± 50.99) pg/mL, P <0.05]. At the same time, there was no signif-icant changes in the plasma IL-10 level [(345.96 ± 67.72) pg/mL, (345.30 ± 78.52) pg/mL, P > 0.05]. Whereas TNF-α level in BALF was significantly decreased [(130.94 ± 33.51) pg/mL, (106.59 ± 26.64) pg/ mL, P < 0. 05, so was the IL-1 level in BALF (82.5 ± 25.36) pg/mL, (63.89 ± 22.96) pg/mL, P < 0. 05], but IL-10 level in the BALF was significantly increased[(77.09 ± 26.05) pg/mL, (148.05 ± 53.50) pg/mL, P <0.01]. DD significantly reduced the nueleoprotein level of PAM[(5.35 ± 2.44) μg/μL, (3.54 ± 2.01) μg/ μL, P < 0.05]and significantly inhibited the NF-κB activity [electrophoretic band optical density × area/consult mtio(1.45±0.71),(1.11±0.28), P <0.05]aswell. Conclusions DD regulated systemic pro-inflammato-ry media/anti-inflammatory media balance in rats with ARDS by mainly reducing the level of IL-1. The regulatory effects of DD on the local lung injury not only inhibit the producing of TNF-α and IL-1 level,but also increase the IL-10 level to reestablish the local pro-inflammatory factors/anti-inflammatory factors balance so as to inhibit the lo-cal excessive irranune response. DD inhibits the NF-κB activity in the PAM of ARDS rats so as to restrain the pro-duction of pro-inflammatory cytokines (TNF-α and IL-1). This kind of multi-target bidirectional regulation plays an active role in regulating the immune balance and protecting the target organ from the excessive injury.