苍果喷雾剂预防呼吸道病毒感染的研究
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摘要
目的：
呼吸道病毒感染性疾病是威胁人类健康的常见病、多发病。病毒疫苗只能预防特异的某些病毒却不能适应病毒不断变异,而且针对呼吸道病毒的西药既有较强的毒副作用,又容易诱导病毒产生耐药性。依据中医药预防疫病经验和中医外治法优点,在中医药中寻找有效药物、创造新型药剂来预防呼吸道病毒感染就成为一项很有意义的研究工作。
苍果喷雾剂是由苍术、草果、荆芥、香薷、藿香、薄荷、丁香提取的挥发油加入冰片组成的中药复方咽部黏膜给药制剂,是根据中医疫病预防“治未病”、“整体观念”思想和“扶正祛邪”原则,结合芳香辟秽法研制而成,具有疏风解表,芳香辟秽,化湿和中的功效,用于呼吸道病毒感染的预防。首先体外实验进行苍果喷雾剂抗流感病毒、呼吸道合胞病毒、腺病毒、柯萨奇病毒的研究,观察其预防常见呼吸道病毒感染发生的作用。体内实验采用流感病毒亚甲型鼠肺适应株(FM1)感染小鼠作为模型,观察苍果喷雾剂对FM1感染小鼠的抗病毒作用及其对免疫功能的影响,尤其是对非特异性免疫中呼吸道黏膜免疫的影响,探讨其预防呼吸道病毒感染的作用和免疫调节作用的分子机制。通过以上研究期望能为中药复方咽部黏膜给药预防呼吸道病毒感染的研究和推广应用提供理论依据和实验依据。
方法：
1.苍果喷雾剂抗4种病毒感染的体外实验研究方法：选择每种病毒的敏感细胞,进行单层细胞抑制抗病毒实验,了解苍果喷雾剂抗流感病毒(H3N2)、呼吸道合胞病毒(RSV)、肠道柯萨奇病毒(CVA16)、腺病毒(Ad3)的效果。
2.苍果喷雾剂抗甲型流感病毒FM1感染的体内实验研究方法：(1)苍果喷雾剂对FM1感染小鼠肺指数的影响,将昆明小鼠随机分为七组：空白对照组、模型对照组、阳性药对照组(利巴韦林)、苍果喷雾剂溶剂对照组、苍果喷雾剂高、中、低剂量组,以15LD5o流感病毒FM1株病毒液滴鼻吸入感染小鼠造模,50μl/只。空白对照组以50μl生理盐水滴鼻。造模前2天开始经咽部喷雾给药,连续给药7天。空白对照组和模型对照组给予生理盐水。末次给药24h后,称体重,处死小鼠,摘取肺脏,计算肺指数。取肺组织做HE染色观察肺部病理变化。(2)苍果喷雾剂对FM1感染小鼠免疫功能的影响,动物分组、造模、给药方法同上。取血采用流式细胞技术检测T淋巴细胞亚群和NK细胞的含量。摘取小鼠肺脏进行匀浆,和小鼠血浆一起采用ELISA方法检测促炎因子TNF-α、IFN-γIL-2、IL-6、IL-8和抗炎因子IL-4、IFN-α的含量。取咽部黏膜,用ELISA检测黏膜匀浆中SIgA、CD54含量；用免疫组化法检测黏膜中CD54、CD106的含量。
结果：
1.苍果喷雾剂抗4种病毒感染的体外实验研究结果：苍果喷雾剂体外抗H3N2、RSV、 CVA16、Ad3病毒实验结果表明,在不同加药方式时,苍果喷雾剂能够有效地提高对H3N2、 RSV、CVA16病毒抑制率,对H3N2、RSV、CVA16有抑制病毒吸附的作用和直接杀病毒作用,对H3N2、RSV病毒吸附后在细胞内的复制增殖有抑制作用,对Ad3无明显抑制作用。
2.苍果喷雾剂抗甲型流感病毒FM1感染的体内实验研究结果：(1)苍果喷雾剂对FM1感染小鼠肺指数的影响实验结果,即小鼠感染流感病毒后肺指数显著升高,苍果喷雾剂高、中、低剂量组可以有效抑制因病毒感染引起的小鼠肺指数增高,改善肺组织病理变化,且呈现剂量依赖,与溶剂对照组比较均有显著差异(P<0.05)。(2)苍果喷雾剂对FM1感染小鼠免疫功能的影响实验结果,即用流式细胞检测小鼠感染流感病毒FM1后血中T淋巴细胞亚群的CD3+、CD4+、CD4+/CD8+比值显著下降,CD8+明显升高,且NK细胞均明显下降。苍果喷雾剂各剂量组可有效地升高T淋巴细胞亚群的CD3+、CD4+、CD4+/CD8+比值和NK细胞含量,降低T淋巴细胞亚群的CD8+含量。ELISA检测小鼠感染流感病毒后血浆中IL-2、IL-4、IFN-α含量明显减低,IL-6、IL-8含量明显升高。苍果喷雾剂各药物组血浆中IL-2、IL-4、IFN-α含量升高,而IL-6、IL-8降低。ELISA检测小鼠感染流感病毒后肺匀浆中TNF-α IFN-γ含量明显升高,苍果挥喷雾剂各剂量组能降低肺中IFN-γ、TNF-α含量;免疫组化检测小鼠感染流感病毒后咽部黏膜中CD54、CD106含量明显升高,与ELISA检测黏膜匀浆中CD54升高相符,且小鼠感染流感病毒后咽部黏膜匀浆中SlgA含量显著降低。苍果喷雾剂各剂量组有明显升高SIgA和降低CD54、CD106的作用。各实验检测均呈现剂量依赖,苍果喷雾剂各剂量组与溶剂对照组比较均有显著差异(P<0.05)。
结论：
1.本研究从中医预防疫病的理论核心“治未病”、理论基础“整体观念”、基本原则“扶正祛邪”等方面进行理论研究,阐述中药外治法预防呼吸道病毒感染的作用机理和优势,以及中西医预防呼吸道病毒感染研究概况,再对中药苍果喷雾剂经黏膜给药预防呼吸道病毒感染进行实验研究和预防观察,为临床推广应用中药黏膜给药预防呼吸道病毒感染提供理论依据和实验依据。
2.体外实验证实苍果喷雾剂对甲型流感病毒H3N2、RSV、CVA16有抑制病毒吸附和直接杀病毒作用,对H3N2、RSV病毒吸附后在细胞内的复制增殖有抑制作用,对Ad3无抗病毒作用。表明苍果喷雾剂不但能够预防呼吸道病毒感染,而且对呼吸道病毒感染还有早期治疗作用。
3.体内实验证明苍果喷雾剂是预防呼吸道病毒感染的有效方剂,可降低肺指数,对甲型流感病毒FM1感染小鼠的肺组织损伤有改善作用。苍果喷雾剂能增加NK细胞、IFN-α含量增强非特异性免疫,并且通过调节T细胞亚群,降低促炎因子和升高抗炎因子表达,减轻炎性病理损伤,进而恢复细胞免疫和体液免疫功能的稳定和平衡,增强机体抵御呼吸道病毒的能力。苍果喷雾剂可以通过下调咽部黏膜中黏附分子CD54、CD106的表达,增加咽部SIgA的含量,增强机体咽部黏膜免疫抵御病毒的功能,中和病毒,抑制病毒吸附和入侵,发挥其预防呼吸道病毒感染的作用。
Objective:
Respiratory viral infection is a a clinical frequent disease and common disease of the threat to human health. Only some of the specific virus could be prevented by vaccine, but vaccine could not adapt to the virus mutation. The western medicine for respiratory viruses not only had strong side effects, but also easyly induced virus resistance. It will become a meaningful research to find effective drugs in Chinese medicine to create new pharmaceutical for the prevention of respiratory viral infections, based on the experience in prevention of epidemic diseases with Chinese medicine. Cangguo sprays was mucosal drug delivery formulations of traditional Chinese medicine(TCM), it was composed of borneol and the extracted volatile oil of the herb, caoguo, nepeta, elsholtzia, wrinkled giant hyssop, mint, cloves. Cangguo sprays was researched according to the theory of preventive treatment of disease and holistic concept and the principle of Fuzheng quxie in prevention of epidemic diseases in TCM, and combined with the by aromatic drugs, then it had the efficacy of dispelling wind and relieving, dispelling turbidness and dampness. In this study, the Asian influenza mouse lung to adapt to the strain (FM1) of influenza virus infected mice as a model, there were observed the effect of antiviral infected and the impact on immune function of Cangguo sprays, especially the impact of Cangguo sprays on non-specific immunity in the respiratory tract mucosal immunity, to explore its role in prevention of respiratory viral infections and immune regulation of the molecular mechanisms. And in vitro experiments there were carried out anti-influenza virus, respiratory syncytial virus, adenovirus, Coxsackie virus, and observed the role of prevention of common respiratory viral infections diseases of Cangguo sprays. Provide a theoretical basis for research and promote the use of Cangguo sprays.
Methods:
1. Cangguo sprays against four kinds of viral infections in vitro
Monolayer cells inhibit anti-viral experiment werw researched by selecting for each virus-sensitive cells,, and observed the effect of anti-virus infection of Cangguo sprays on influenza virus A (H3N2), respiratory syncytial virus (RSV), intestinal Coxsackie virus (CVA16), adenovirus (Ad3).
2. Cangguo sprays against FM1infected in vivo
(1) lung index in FM1infected mice with Cangguo sprays
Kunming mice were randomly divided into seven groups:blank control group, model control group, positive control (ribavirin), Cangguo sprays solvent control group, Cangguo sprays hign, middle, low dose group, to15LD50influenza virus FM1virus liquid intranasal inhalation of infected mice model,50μl of everyone. Blank control group50μl normal saline intranasally. Modeling the first two days by the throat spray administration administration for consecutive seven days. The blank control group and model control group were given saline.24h after the last dose, mice were weighed and sacrificed, then removed the lung to calculate the lung index. Lung tissue were done HE dyeing to odserve lung pathological changes.
(2) Immune function in FM1infected mice with Cangguo sprays
Animal grouping, modeling, administration method as above. The content of T lymphocyte subsets and NK cells in blood were detected by flow cytometry. By ELISA homogenate of mouse lung and mouse plasma were detected the pro-inflammatory cytokines of TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8and the anti-inflammatory cytokines of IL-4and IFN-α content. The content of CD54and SIgA in the pharyngeal mucosal homogenates were determined by ELISA. Simultaneously the content of CD54and CD106in mucosa were detected immunohistochemical method.
Results:
1.Cangguo sprays against four kinds of viral infections in vitro
In the experimental results of resistance to the H3N2, RSV, CVA16and Ad3viruses in vitro, there were effectively improved the inhibitory rate of H3N2, RSV and CVA16virus with the different dosing of Cangguo sprays. There were inhibited virus adsorption and killed the H3N2, RSV, CVA16virus, then the replication and proliferation of the cells after virus adsorption of the H3N2, RSVand CVA16virus were inhibited with Cangguo sprays. There was no significant inhibitory effect on Ad3.
2. Cangguo sprays against FM1infected in vivo
(1) lung index in FM1infected mice with Cangguo sprays
Lung index of mice infected with influenza virus were significantly elevated. With Cangguo sprays there were effectively inhibited the increased lung index, and there were improved the pathological changes of lung tissue and were dose-dependented. Compared with the solvent control group there were significantly different (P<0.05).
(2) Immune function in FM1infected mice with Cangguo sprays
The T lymphocyte subsets and NK cells in blood of influenza virus FM1mice were detected by Flow cytometry, CD3+, CD4+and CD4+/CD8+ratio were significantly decreased, and CD8+was significantly increased, and NK cells were significantly decreased. With each dose group of Cangguo sprays there were effectively increased CD3+, CD4+, CD4+/CD8+ratio and NK cell levels, and reduced CD8+content. By ELISA detection of the plasma of mice infected with influenza virus, the contents of IL-2, IL-4and IFN-a were significantly reduced and the contents of IL-6, IL-8were significantly increased. With each dose group of Cangguo sprays there were effectively increased the contents of IL-2, IL-4and IFN-a, and reduced the contents of IL-6, IL-8. By ELISA detection of lung homogenate of mice infected with influenza virus the contents of TNF-alpha and IFN-y were significantly elevated. With each dose group of Cangguo sprays the contents of TNF-alpha and IFN-y were effectively reduced. The contents of CD54and CD106of pharyngeal mucosa of mice infected with influenza virus with immunohistochemical detection were significantly increased, similarly the content of CD54of pharyngeal mucosal homogenate with the ELISA detection was increased, but the content of SIgA of pharyngeal mucosal homogenate with the ELISA detection was significantly reduced. With each dose group of Cangguo sprays, there were effectively reduced the contents of CD54and CD106, and effectively increased the content of SIgA.There were dose-dependent in each assay of Cangguo sprays. When each dose group of Cangguo sprays compared with the solvent control group, there were significantly different (P<0.05).
Conclusion:
1. In this paper, the theoretical research was according to the theoretical core of preventive treatment of disease, the theoretical basis of holistic concept and the basic principle of Fuzheng quxie in prevention of epidemic diseases in TCM. There were expounded the mechanism and advantages of prevention of respiratory virual infection with the external treatment of TCM, and there were elaborated the research overview of prevention of respiratory virual infection with TCM and western medicine. Then though experiment research and clinical prevent observation with Cangguo sprays, there were provided theoretical basis and experimental evidence for the clinical application of mucosal administration medicine of TCM for prevention of respiratory virus infections.
2. There were effectively improved the inhibitory rate of H3N2, RSV and CVA16virus with the different dosing of Cangguo sprays in vitro. There were inhibited virus adsorption and killed the H3N2, RSV, CVA16virus, then the replication and proliferation of the cells after virus adsorption of the H3N2, RSVand CVA16virus were inhibited with Cangguo sprays. There was no significant inhibitory effect on Ad3.
3. Cangguo sprays is an effective prescription for the prevention of respiratory viral infection. Lung index and lung tissue damage of FM1infected mice could be reduced with Cangguo sprays. It could be enhanced on non-specific immunity by increase the contents of NK cells and IFN-a with Cangguo sprays. Through the regulation of T cell subsets, reduce of pro-inflammatory cytokines and increase of anti-inflammatory factor, reduce of the inflammatory pathological damage, there were restored the stability and balance between cellular immunity and humoral immune function, then to enhance the ability of body to resist against respiratory viruses with Cangguo sprays.The expression of CD54and CD106in the pharyngeal mucosa could be reduced and the expression of SIgA in the pharyngeal mucosa could be increased with Cangguo sprays. By strengthening of the pharyngeal mucosa immunization against the virus function, and improving of neutralizing acttvity, and addition of the inhibition of virus attachment and invasion, there were enhanced the role of against respiratory viruses with Cangguo sprays.
呼吸道病毒感染性疾病是威胁人类健康的常见病、多发病。病毒疫苗只能预防特异的某些病毒却不能适应病毒不断变异,而且针对呼吸道病毒的西药既有较强的毒副作用,又容易诱导病毒产生耐药性。依据中医药预防疫病经验和中医外治法优点,在中医药中寻找有效药物、创造新型药剂来预防呼吸道病毒感染就成为一项很有意义的研究工作。
苍果喷雾剂是由苍术、草果、荆芥、香薷、藿香、薄荷、丁香提取的挥发油加入冰片组成的中药复方咽部黏膜给药制剂,是根据中医疫病预防“治未病”、“整体观念”思想和“扶正祛邪”原则,结合芳香辟秽法研制而成,具有疏风解表,芳香辟秽,化湿和中的功效,用于呼吸道病毒感染的预防。首先体外实验进行苍果喷雾剂抗流感病毒、呼吸道合胞病毒、腺病毒、柯萨奇病毒的研究,观察其预防常见呼吸道病毒感染发生的作用。体内实验采用流感病毒亚甲型鼠肺适应株(FM1)感染小鼠作为模型,观察苍果喷雾剂对FM1感染小鼠的抗病毒作用及其对免疫功能的影响,尤其是对非特异性免疫中呼吸道黏膜免疫的影响,探讨其预防呼吸道病毒感染的作用和免疫调节作用的分子机制。通过以上研究期望能为中药复方咽部黏膜给药预防呼吸道病毒感染的研究和推广应用提供理论依据和实验依据。
方法：
1.苍果喷雾剂抗4种病毒感染的体外实验研究方法：选择每种病毒的敏感细胞,进行单层细胞抑制抗病毒实验,了解苍果喷雾剂抗流感病毒(H3N2)、呼吸道合胞病毒(RSV)、肠道柯萨奇病毒(CVA16)、腺病毒(Ad3)的效果。
2.苍果喷雾剂抗甲型流感病毒FM1感染的体内实验研究方法：(1)苍果喷雾剂对FM1感染小鼠肺指数的影响,将昆明小鼠随机分为七组：空白对照组、模型对照组、阳性药对照组(利巴韦林)、苍果喷雾剂溶剂对照组、苍果喷雾剂高、中、低剂量组,以15LD5o流感病毒FM1株病毒液滴鼻吸入感染小鼠造模,50μl/只。空白对照组以50μl生理盐水滴鼻。造模前2天开始经咽部喷雾给药,连续给药7天。空白对照组和模型对照组给予生理盐水。末次给药24h后,称体重,处死小鼠,摘取肺脏,计算肺指数。取肺组织做HE染色观察肺部病理变化。(2)苍果喷雾剂对FM1感染小鼠免疫功能的影响,动物分组、造模、给药方法同上。取血采用流式细胞技术检测T淋巴细胞亚群和NK细胞的含量。摘取小鼠肺脏进行匀浆,和小鼠血浆一起采用ELISA方法检测促炎因子TNF-α、IFN-γIL-2、IL-6、IL-8和抗炎因子IL-4、IFN-α的含量。取咽部黏膜,用ELISA检测黏膜匀浆中SIgA、CD54含量；用免疫组化法检测黏膜中CD54、CD106的含量。
结果：
1.苍果喷雾剂抗4种病毒感染的体外实验研究结果：苍果喷雾剂体外抗H3N2、RSV、 CVA16、Ad3病毒实验结果表明,在不同加药方式时,苍果喷雾剂能够有效地提高对H3N2、 RSV、CVA16病毒抑制率,对H3N2、RSV、CVA16有抑制病毒吸附的作用和直接杀病毒作用,对H3N2、RSV病毒吸附后在细胞内的复制增殖有抑制作用,对Ad3无明显抑制作用。
2.苍果喷雾剂抗甲型流感病毒FM1感染的体内实验研究结果：(1)苍果喷雾剂对FM1感染小鼠肺指数的影响实验结果,即小鼠感染流感病毒后肺指数显著升高,苍果喷雾剂高、中、低剂量组可以有效抑制因病毒感染引起的小鼠肺指数增高,改善肺组织病理变化,且呈现剂量依赖,与溶剂对照组比较均有显著差异(P<0.05)。(2)苍果喷雾剂对FM1感染小鼠免疫功能的影响实验结果,即用流式细胞检测小鼠感染流感病毒FM1后血中T淋巴细胞亚群的CD3+、CD4+、CD4+/CD8+比值显著下降,CD8+明显升高,且NK细胞均明显下降。苍果喷雾剂各剂量组可有效地升高T淋巴细胞亚群的CD3+、CD4+、CD4+/CD8+比值和NK细胞含量,降低T淋巴细胞亚群的CD8+含量。ELISA检测小鼠感染流感病毒后血浆中IL-2、IL-4、IFN-α含量明显减低,IL-6、IL-8含量明显升高。苍果喷雾剂各药物组血浆中IL-2、IL-4、IFN-α含量升高,而IL-6、IL-8降低。ELISA检测小鼠感染流感病毒后肺匀浆中TNF-α IFN-γ含量明显升高,苍果挥喷雾剂各剂量组能降低肺中IFN-γ、TNF-α含量;免疫组化检测小鼠感染流感病毒后咽部黏膜中CD54、CD106含量明显升高,与ELISA检测黏膜匀浆中CD54升高相符,且小鼠感染流感病毒后咽部黏膜匀浆中SlgA含量显著降低。苍果喷雾剂各剂量组有明显升高SIgA和降低CD54、CD106的作用。各实验检测均呈现剂量依赖,苍果喷雾剂各剂量组与溶剂对照组比较均有显著差异(P<0.05)。
结论：
1.本研究从中医预防疫病的理论核心“治未病”、理论基础“整体观念”、基本原则“扶正祛邪”等方面进行理论研究,阐述中药外治法预防呼吸道病毒感染的作用机理和优势,以及中西医预防呼吸道病毒感染研究概况,再对中药苍果喷雾剂经黏膜给药预防呼吸道病毒感染进行实验研究和预防观察,为临床推广应用中药黏膜给药预防呼吸道病毒感染提供理论依据和实验依据。
2.体外实验证实苍果喷雾剂对甲型流感病毒H3N2、RSV、CVA16有抑制病毒吸附和直接杀病毒作用,对H3N2、RSV病毒吸附后在细胞内的复制增殖有抑制作用,对Ad3无抗病毒作用。表明苍果喷雾剂不但能够预防呼吸道病毒感染,而且对呼吸道病毒感染还有早期治疗作用。
3.体内实验证明苍果喷雾剂是预防呼吸道病毒感染的有效方剂,可降低肺指数,对甲型流感病毒FM1感染小鼠的肺组织损伤有改善作用。苍果喷雾剂能增加NK细胞、IFN-α含量增强非特异性免疫,并且通过调节T细胞亚群,降低促炎因子和升高抗炎因子表达,减轻炎性病理损伤,进而恢复细胞免疫和体液免疫功能的稳定和平衡,增强机体抵御呼吸道病毒的能力。苍果喷雾剂可以通过下调咽部黏膜中黏附分子CD54、CD106的表达,增加咽部SIgA的含量,增强机体咽部黏膜免疫抵御病毒的功能,中和病毒,抑制病毒吸附和入侵,发挥其预防呼吸道病毒感染的作用。
Objective:
Respiratory viral infection is a a clinical frequent disease and common disease of the threat to human health. Only some of the specific virus could be prevented by vaccine, but vaccine could not adapt to the virus mutation. The western medicine for respiratory viruses not only had strong side effects, but also easyly induced virus resistance. It will become a meaningful research to find effective drugs in Chinese medicine to create new pharmaceutical for the prevention of respiratory viral infections, based on the experience in prevention of epidemic diseases with Chinese medicine. Cangguo sprays was mucosal drug delivery formulations of traditional Chinese medicine(TCM), it was composed of borneol and the extracted volatile oil of the herb, caoguo, nepeta, elsholtzia, wrinkled giant hyssop, mint, cloves. Cangguo sprays was researched according to the theory of preventive treatment of disease and holistic concept and the principle of Fuzheng quxie in prevention of epidemic diseases in TCM, and combined with the by aromatic drugs, then it had the efficacy of dispelling wind and relieving, dispelling turbidness and dampness. In this study, the Asian influenza mouse lung to adapt to the strain (FM1) of influenza virus infected mice as a model, there were observed the effect of antiviral infected and the impact on immune function of Cangguo sprays, especially the impact of Cangguo sprays on non-specific immunity in the respiratory tract mucosal immunity, to explore its role in prevention of respiratory viral infections and immune regulation of the molecular mechanisms. And in vitro experiments there were carried out anti-influenza virus, respiratory syncytial virus, adenovirus, Coxsackie virus, and observed the role of prevention of common respiratory viral infections diseases of Cangguo sprays. Provide a theoretical basis for research and promote the use of Cangguo sprays.
Methods:
1. Cangguo sprays against four kinds of viral infections in vitro
Monolayer cells inhibit anti-viral experiment werw researched by selecting for each virus-sensitive cells,, and observed the effect of anti-virus infection of Cangguo sprays on influenza virus A (H3N2), respiratory syncytial virus (RSV), intestinal Coxsackie virus (CVA16), adenovirus (Ad3).
2. Cangguo sprays against FM1infected in vivo
(1) lung index in FM1infected mice with Cangguo sprays
Kunming mice were randomly divided into seven groups:blank control group, model control group, positive control (ribavirin), Cangguo sprays solvent control group, Cangguo sprays hign, middle, low dose group, to15LD50influenza virus FM1virus liquid intranasal inhalation of infected mice model,50μl of everyone. Blank control group50μl normal saline intranasally. Modeling the first two days by the throat spray administration administration for consecutive seven days. The blank control group and model control group were given saline.24h after the last dose, mice were weighed and sacrificed, then removed the lung to calculate the lung index. Lung tissue were done HE dyeing to odserve lung pathological changes.
(2) Immune function in FM1infected mice with Cangguo sprays
Animal grouping, modeling, administration method as above. The content of T lymphocyte subsets and NK cells in blood were detected by flow cytometry. By ELISA homogenate of mouse lung and mouse plasma were detected the pro-inflammatory cytokines of TNF-alpha, IFN-gamma, IL-2, IL-6, IL-8and the anti-inflammatory cytokines of IL-4and IFN-α content. The content of CD54and SIgA in the pharyngeal mucosal homogenates were determined by ELISA. Simultaneously the content of CD54and CD106in mucosa were detected immunohistochemical method.
Results:
1.Cangguo sprays against four kinds of viral infections in vitro
In the experimental results of resistance to the H3N2, RSV, CVA16and Ad3viruses in vitro, there were effectively improved the inhibitory rate of H3N2, RSV and CVA16virus with the different dosing of Cangguo sprays. There were inhibited virus adsorption and killed the H3N2, RSV, CVA16virus, then the replication and proliferation of the cells after virus adsorption of the H3N2, RSVand CVA16virus were inhibited with Cangguo sprays. There was no significant inhibitory effect on Ad3.
2. Cangguo sprays against FM1infected in vivo
(1) lung index in FM1infected mice with Cangguo sprays
Lung index of mice infected with influenza virus were significantly elevated. With Cangguo sprays there were effectively inhibited the increased lung index, and there were improved the pathological changes of lung tissue and were dose-dependented. Compared with the solvent control group there were significantly different (P<0.05).
(2) Immune function in FM1infected mice with Cangguo sprays
The T lymphocyte subsets and NK cells in blood of influenza virus FM1mice were detected by Flow cytometry, CD3+, CD4+and CD4+/CD8+ratio were significantly decreased, and CD8+was significantly increased, and NK cells were significantly decreased. With each dose group of Cangguo sprays there were effectively increased CD3+, CD4+, CD4+/CD8+ratio and NK cell levels, and reduced CD8+content. By ELISA detection of the plasma of mice infected with influenza virus, the contents of IL-2, IL-4and IFN-a were significantly reduced and the contents of IL-6, IL-8were significantly increased. With each dose group of Cangguo sprays there were effectively increased the contents of IL-2, IL-4and IFN-a, and reduced the contents of IL-6, IL-8. By ELISA detection of lung homogenate of mice infected with influenza virus the contents of TNF-alpha and IFN-y were significantly elevated. With each dose group of Cangguo sprays the contents of TNF-alpha and IFN-y were effectively reduced. The contents of CD54and CD106of pharyngeal mucosa of mice infected with influenza virus with immunohistochemical detection were significantly increased, similarly the content of CD54of pharyngeal mucosal homogenate with the ELISA detection was increased, but the content of SIgA of pharyngeal mucosal homogenate with the ELISA detection was significantly reduced. With each dose group of Cangguo sprays, there were effectively reduced the contents of CD54and CD106, and effectively increased the content of SIgA.There were dose-dependent in each assay of Cangguo sprays. When each dose group of Cangguo sprays compared with the solvent control group, there were significantly different (P<0.05).
Conclusion:
1. In this paper, the theoretical research was according to the theoretical core of preventive treatment of disease, the theoretical basis of holistic concept and the basic principle of Fuzheng quxie in prevention of epidemic diseases in TCM. There were expounded the mechanism and advantages of prevention of respiratory virual infection with the external treatment of TCM, and there were elaborated the research overview of prevention of respiratory virual infection with TCM and western medicine. Then though experiment research and clinical prevent observation with Cangguo sprays, there were provided theoretical basis and experimental evidence for the clinical application of mucosal administration medicine of TCM for prevention of respiratory virus infections.
2. There were effectively improved the inhibitory rate of H3N2, RSV and CVA16virus with the different dosing of Cangguo sprays in vitro. There were inhibited virus adsorption and killed the H3N2, RSV, CVA16virus, then the replication and proliferation of the cells after virus adsorption of the H3N2, RSVand CVA16virus were inhibited with Cangguo sprays. There was no significant inhibitory effect on Ad3.
3. Cangguo sprays is an effective prescription for the prevention of respiratory viral infection. Lung index and lung tissue damage of FM1infected mice could be reduced with Cangguo sprays. It could be enhanced on non-specific immunity by increase the contents of NK cells and IFN-a with Cangguo sprays. Through the regulation of T cell subsets, reduce of pro-inflammatory cytokines and increase of anti-inflammatory factor, reduce of the inflammatory pathological damage, there were restored the stability and balance between cellular immunity and humoral immune function, then to enhance the ability of body to resist against respiratory viruses with Cangguo sprays.The expression of CD54and CD106in the pharyngeal mucosa could be reduced and the expression of SIgA in the pharyngeal mucosa could be increased with Cangguo sprays. By strengthening of the pharyngeal mucosa immunization against the virus function, and improving of neutralizing acttvity, and addition of the inhibition of virus attachment and invasion, there were enhanced the role of against respiratory viruses with Cangguo sprays.
引文
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