Comparative Study on the Pharmacodynamics of Xiangzhu Fanggan Formula(香术防感方)by Sniffing and Nasal Drops for Prevention of Influenza A H1N1 Virus Infection in Mice
ABSTRACT Objective To compare the effectiveness and mechanism of Xiangzhu Fanggan Formula(香术防感方)by sniffing and nasal drops for preventing influenza A H1N1flu.Methods Fifty-six BALB/c mice were random-ly divided into normal group,model group,zanamivir group,high-concentration sachet group,low-concentration sa-chet group,high-concentration nasal drops group,and low-concentration nasal drops group,with 8 mice in each group.In the low-and high-concentration sachet groups,15 g and 30 g of Xiangzhu Fanggan Formula sachet were used for sniffing for 24 h per day;while in the low-and high-concentration nasal drops groups,nasal drops of Xiangzhu Fanggan Formula were given at a concentration of 0.11 and 0.22 g/ml,20 μl each time,twice a day;in the zanami-vir group,zanamivir was given at a concentration of 1.025 mg/ml of 20 μl each time,twice a day;in the normal group and the model group,nasal drops of normal saline were given at 20 μl each time,twice a day.Each group was given prophylactic intervention for 5 days.On day 5,1 h after the administration of the drug,the mice in all groups except the normal group received 35 μl of 50 LD50A/PR/8/34/H1N1 viral solution as nasal drops to prepare influenza A H1N1 model mice.The body mass of the mice was recorded and the rate of change of body mass was calculated daily from day 5 to day 9 of the experiment,and the general status was observed.The mice were sampled on day 9,and the lung index and the inhibition rate of lung index were calculated;HE staining was used to detect pathological changes in lung tissues and to score lung tissue lesions;RT-qPCR was used to detect viral load in lung tissues;and ELISA was used to detect secretory immunoglobulin A(sIgA)and serum tumour necrosis factor α(TNF-α)and interleukin 2(IL-2),interleukin 6(IL-6),and interferon γ(IFN-γ)in the lavage fluid of the upper respiratory tract.Results On days 7,8 and 9 of the experiment,the rate of change in body mass of mice in the model group significantly lower than that in the normal group at the same time points(P＜0.05 or P＜0.01).On days 8 and 9 of the experiment,the rate of change in body mass of mice in the zanamivir group and the high-concentration nasal drops group increased when compared with the model group(P＜0.05 or P＜0.01).Compared with the normal group,mice in the model group had significantly higher lung index,lung tissue lesion score,lung tissue viral load,significantly higher serum TNF-α,IL-6,IL-2,IFN-γ levels,and significantly lower sIgA levels in the upper respiratory lavage fluid(P＜0.01).Com-pared with the model group,the lung index and lung tissue viral load reduced,serum IFN-γ,TNF-α,IL-2,IL-6 levels reduced,and sIgA levels increased in the zanamivir group and the high-concentration nosal drops group(P＜0.05 or P＜0.01);except for low-concentration sachet group,lung tissue lesion scores of the drug intervention groups reduced compared with those of the model group(P＜0.01).Compared with the zanamivir group,the lung index increased in the low-concentration sachet group and the low-and high-concentration nasal drops groups,and the serum TNF-α and IL-2 levels increased in all Xiangzhu Fanggan Formula intervention groups(P＜0.05 or P＜0.01).Compared with high-concentration nasal drops group,serum TNF-α and IFN-γ levels elevated in the high-concen-tration increased group,and lung tissue viral load elevated in the low-concentration nasal drops group(P＜0.05 or P＜0.01).The lung index inhibition rate was 80.84％in the zanamivir group,41.61％and 17.90％in the high-and low-concentration sachet groups,and 35.40％and 25.40％in the high-and low-concentration nasal drops groups,re-spectively.HE staining showed that the lung tissues of the model group showed thickening of alveolar septa,alveolar collapse,and infiltration of inflammatory cells;whereas,in each drug intervention group,the inflammation of the lung tissues of the mice and the damage reduced,and the most obvious improvement was in the zanamivir group and the high-concentration nasal drops group.Conclusion Xiangzhu Fanggan Formula by sniffing and nasal drops could both prevent influenza A H1N1 virus infection,with antiviral and anti-inflammatory effects,also could improve the pathological damage of lung tissue,and improve the immunity of respiratory mucosa.The nasal drops may be better than sachets in inhibiting inflammatory response,especially the high-concentration nasal drops showed more effective.
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