马兜铃配伍生地黄对其止咳平喘作用的影响

Effects of Aristolochia debilis combined with raw Rehmannia glutinosa on its antitussive and antiasthmatic impact

为了探究将马兜铃与生地黄配伍降低马兜铃的毒性是否会影响其止咳平喘作用及能否达到减毒存效的作用,试验将豚鼠随机分为5组,分别为空白对照组(灌胃生理盐水)、卵清蛋白(OVA)模型组(灌胃生理盐水)、OVA+马兜铃组(灌胃马兜铃水煎剂,按体重15 g/kg)、OVA+配伍组(灌胃马兜铃与生地黄按体积比4∶1配伍的水煎剂,马兜铃生药含量同OVA+马兜铃组)、OVA+生地黄组(灌胃生地黄水煎剂,生地黄生药含量同OVA+配伍组),除空白对照组外,其他各组均于试验开始的第1天腹腔注射10%OVA溶液使受试豚鼠致敏,建立咳喘模型后,在第16~21天按组灌胃给药,每天1次。观察各组豚鼠咳喘情况;检测血液和肺泡灌洗液(BALF)中白细胞数、嗜酸性粒细胞数,BALF中免疫球蛋白E(IgE)、肿瘤坏死因子-α(TNF-α)质量浓度及血清中γ干扰素(IFN-γ)、白细胞介素-4(IL-4)和白细胞介素-5(IL-5)质量浓度;观察豚鼠肺脏和肾脏组织病理学变化。结果表明:通过OVA致敏成功构建豚鼠咳喘模型;在灌胃给药6 d后,各组豚鼠肾脏组织结构未见异常改变。与空白对照组相比,OVA致敏各组豚鼠的引喘潜伏期均显著缩短(P<0.05),咳嗽次数、激发行为学评分均显著增加(P<0.05),BALF中白细胞数、嗜酸性粒细胞百分比及IgE、TNF-α质量浓度均显著增加(P<0.05),血清中IL-4及IL-5质量浓度均显著增加(P<0.05),IFN-γ质量浓度显著降低(P<0.05)。OVA模型组豚鼠肺脏组织基本结构消失,存在大量水肿、充血、炎性细胞浸润等现象,而OVA+马兜铃组和OVA+配伍组豚鼠肺脏组织病理损伤情况较OVA模型组明显减轻。与OVA模型组相比,OVA+马兜铃组和OVA+配伍组的引喘潜伏期和血清中IFN-γ质量浓度均显著提高(P<0.05),咳嗽次数、激发行为学评分,外周血中白细胞数、嗜酸性粒细胞数,BALF中白细胞数、嗜酸性粒细胞百分比及IgE、TNF-α质量浓度,血清中IL-4、IL-5质量浓度均显著降低(P<0.05)。说明生地黄配伍仍保留马兜铃止咳、平喘、消炎等药理作用。

In order to explore whether Aristolochia debilis combined with raw Rehmannia glutinosa could reduce the toxicity of Aristolochia debilis,its effect on the antitussive and antiasthmatic impact,and whether it could achieve the effect of attenuating and preserving efficacy,in the experiment,Guinea pigs were randomly divided into 5 groups,which were blank control group(gavage saline),OVA model group(gavage with saline),OVA+Aristolochia debilis group(gavage with Aristolochia debilis decoction,15 g/kg by body weight),OVA+compatibility group(gavage with Aristolochia debilis and raw Rehmannia glutinosa were 4∶1 compatible decoction,and the crude drug content of Aristolochia debilis was the same as that of OVA+Aristolochia debilis group)and OVA+raw Rehmannia glutinosa group(gavage with raw Rehmannia glutinosa decoction,the crude drug content of gavage with raw Rehmannia glutinosa was the same as that of OVA+compatibility group).Except for the blank control group,all other groups were intraperitoneally injected with 10%OVA solution on the first day of the trial to sensitize the tested guinea pigs.After the cough and asthma model was established,on the 16th-21st day,the drug was administered by gavage according to the grouping method once a day.The coughing and wheezing of guinea pigs in each group were observed.The number of white blood cells,eosinophils,and the mass concentrations of immunoglobulin E(IgE),tumor necrosis factor-α(TNF-α)in blood and alveolar lavage fluid(BALF),andγinterferon(IFN-γ),interleukin-4(IL-4)and interleukin-5(IL-5)in serum were detected.The histopathological changes of guinea pigs'lung and kidney were observed.The results showed that the guinea pig cough and asthma model was successfully constructed by OVA sensitization.After 6 days of gavage,there was no abnormal change in the kidney tissue structure of guinea pigs in each group.Compared with the blank control group,the incubation latency of guinea pigs in each group sensitized by OVA was significantly reduced(P<0.05).The number of coughs and the score of provocative behavior were significantly increased(P<0.05);the number of white blood cells,the percentage of eosinophils,and the concentrations of IgE and TNF-αin BALF were significantly increased(P<0.05);the serum mass concentrations of IL-4 and IL-5 were significantly increased(P<0.05)and the concentration of IFN-γwas significantly reduced(P<0.05).The basic structure of guinea pig lung tissue in the OVA model group disappeared,and there was a large amount of edema,congestion,and inflammatory cell infiltration;in contrast,the histopathological damage of guinea pig lung tissues in the OVA+Aristolochia debilis group and the OVA+compatibility group was significantly reduced compared with the OVA model group.The wheezing latency and serum IFN-γmass concentration were significantly higher in the OVA+Aristolochia debilis group and the OVA+compatibility group compared to the OVA model group(P<0.05);the number of coughs,behavioral scores at the time of elicitation,the number of leukocytes and eosinophils in peripheral blood,the number of leukocytes and percentage of eosinophils and the mass concentrations of IgE and TNF-αin BALF,and the mass concentrations of IL-4 and IL-5 in serum were all significantly reduced(P<0.05).The results indicated that the pharmacological effects of Aristolochia debilis on relieving cough,asthma and inflammation were still retained in the combination of raw Rehmannia glutinosa.