Objective: To investigate the pharmacodynamics and acute toxicity of Duodongan Oral Solution. Methods: The test of walking time and raising the front limbs of mice Step down test were used to observe the improvement of Duodongan Oral Solution on the spontaneous activity inhibition and memory acquisition disturbance of mice. Results: Duodongan Oral solution could obviously inhibit the spontaneous activity of mice, and its action is strengthened with the increase of dosage. The step down test showed that the oral solution could prolong the latent peroid and decrease the error rate in 5 minites, which indicated that the drug obviously improved memory acquisition disturbance. The acute toxic test indicated that the maximum tolerance dose is 159 times as much as the clinical dose a day. Conclusion: This oral solution has much low toxicity, and is safety for oral administration.

OBJECTIVETo evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats.

METHODSForty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups.

RESULTSLevels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all P<0.01. IL-6 was increased in the 2 wk and the 4 wk acrolein exposure group [ (33.28 ± 2.27) ng/L, (46.24 ± 3.16) ng/L] compared with the 2 wk and the 4 wk control group [ (16.37 ± 1.49) ng/L, (17.02 ± 1.43) ng/L] in BALF.Ratio of Th17 was higher in the 2 wk and the 4 wk acrolein exposure groups in peripheral blood (1.82 ± 0.18) %, (3.75 ± 0.48) % and BALF [(7.23 ± 0.27) %, (8.12 ± 0.38) %] compared with the 2 wk [(0.96 ± 0.07) %, (5.64 ± 0.63) %] and the 4 wk control group [(1.01 ± 0.08) %, (5.86 ± 0.57) %]. Ratio of Treg in BALF was higher in the acrolein exposure groups [ (8.83 ± 0.52) %, (12.05 ± 0.74) %] compared with the control groups [(4.37 ± 0.27) %, (5.01 ± 0.37) %]. The level of IL-17 mRNA was increased in the 2 wk and the 4 wk acrolein exposure group in peripheral blood [(25.78 ± 2.31), (34.69 ± 2.01) ] and in BALF [(23.04 ± 1.78), (34.56 ± 3.12)] compared with the 2 wk [(11.04 ± 2.53), (11.08 ± 2.05)] and the 4 wk [(12.03 ± 2.34), (12.69 ± 2.69)] control groups. Foxp3 mRNA was increased in the acrolein exposure groups [ (26.37 ± 3.24), (33.19 ± 2.98)] (24.4 ± 2.7), (30.3 ± 2.7) compared with the control groups [(12.37 ± 2.56), (13.12 ± 3.08)]. Th17 in acrolein exposure groups was positively correlated with counts of total cells and macrophages (r=0.5126, 0.5437, all P<0.01).

CONCLUSIONSA changed expression of Th17 and Treg cells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats.

Acrolein ; toxicity ; Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Cytokines ; metabolism ; Forkhead Transcription Factors ; metabolism ; Inflammation ; metabolism ; Male ; Rats ; Rats, Wistar ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology