犀角地黄汤合银翘散及其单方对小鼠流感病毒性肺炎治疗作用的比较

Comparison of therapeutic effects of Xijiao Dihuang Decoction combined with Yinqiao Powder and its disassembled prescriptions on influenza pneumonia in mice

目的比较截断疗法经典方犀角地黄汤合银翘散及其单方对小鼠流感病毒性肺炎的治疗作用,探究犀角地黄汤和银翘散在截断疗法中的不同作用。方法ICR小鼠和BALB/c小鼠,随机分为正常组、模型组、犀角地黄汤合银翘散组(简称合方组)、犀角地黄汤组、银翘散组、达菲组,除正常组外其余小鼠以流感病毒滴鼻感染,1 h后给药。各组分别以对应的水煎剂或溶液灌胃,每日1次,连续6 d。ICR小鼠观察14 d,记录小鼠体重及生存时间;BALB/c小鼠分别在感染后第2、4、6天取材,光镜下观察肺组织病理切片、RT-PCR法检测肺组织中甲型流感病毒核蛋白(IAV-NP)mRNA水平、ELISA法检测肺组织肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平。结果合方组可提高感染小鼠生存率,延长生存时间,推后死亡极期,效果优于犀角地黄汤组和银翘散组,而犀角地黄汤组优于银翘散组;合方组在第6天可减轻感染小鼠肺组织炎性病理改变,效果优于犀角地黄汤组和银翘散组,犀角地黄汤组比银翘散组病变轻。在第2、4、6天,银翘散组IAV-NP mRNA表达降低,与模型组比较差异有统计学意义(P<0.01),且在第4、6天,银翘散组IAV-NP mRNA表达低于合方组(P<0.01);第4、6天,犀角地黄汤组IAV-NP mRNA表达与模型组比较,差异无统计学意义。在第4、6天,合方组、犀角地黄汤组和银翘散组肺组织TNF-α和IL-6水平低于模型组(P<0.05、P<0.01),合方组肺组织TNF-α和IL-6水平低于犀角地黄汤组和银翘散组(P<0.05、P<0.01)。犀角地黄汤组第6天TNF-α水平低于银翘散组(P<0.05),而其第2、4天IL-6水平低于银翘散组(P<0.01)。结论银翘散以抗病毒作用为主,而犀角地黄汤以抗炎作用为主,两方合用可在病毒感染早期截断病邪深入,又在疾病极期扭转严重炎症,以达到治疗效果。

Objective To compare the therapeutic effects of Xijiao Dihuang Decoction combined with Yinqiao Powder and its disassembled prescription on influenza pneumonia in mice,and to explore the different effects of Xijiao Dihuang Decoction and Yinqiao Powder in the interruptive therapy.Methods ICR mice and BALB/c mice were randomly divided into the normal group,model group,Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)group,Xijiao Dihuang(XD)Decoction group,Yinqiao Powder(YQ)group,and Tamiflu group.The mice in all groups except the normal group were infected with influenza virus by nasal drops.Each group was administered with the corresponding decoction or solution 1 h after infection,once a day for 6 consecutive days.The ICR mice were observed for 14 days,and their weight and survival time were recorded.The BALB/c mice were sampled on the 2nd,4th,and 6th days after infection,and lung tissue pathological sections were observed under the light microscope.The levels of IAV-NP mRNA in lung tissue were detected by RT-PCR,and the levels of TNF-αand IL-6 in lung tissue were detected by ELISA.Results In the XDY group,improved survival rate,prolonged survival time and postponed extreme death period of infected mice were observed,and the effect was better than that of either the XD group or YQ group,with better effect in XD group than YQ group.The effect of the XDY group was better than that of either the XD group or YQ group in alleviating the inflammatory pathological changes of lung tissue infected mice on the 6th day,with the lesions of XD group less than those of YQ group.Compared with the model group,the expression of IAV-NP mRNA in the YQ group was down-regulated on the 2nd,4th and 6th days(P<0.01),and the IAV-NP mRNA expression on the 4th and 6th days was lower than that in the XDY group(P<0.01),while there was no significant difference in the IAV-NP mRNA expression of XD group and the model group on the 4th and 6th days.The levels of TNF-αand IL-6 in lung tissues of the XDY,XD and YQ groups were lower than that of the model group on the 4th and 6th days(P<0.05,P<0.01),with the levels of the XDY group lower than that of either XD or YQ group(P<0.05,P<0.01).The level of TNF-αin XD group on the 6th day was lower than that in YQ group(P<0.05),while the level of IL-6 in XD group on the 2nd,4th days was lower than that in YQ group(P<0.01).Conclusion With an antiviral effect of the Yinqiao Powder and anti-inflammatory effect of the Xijiao Dihuang Decoction,the combination of the two prescriptions seems to stop the pathogen in the early stage of viral infection,and reverse the severe inflammation in the extreme stage to achieve the therapeutic effect.