| Allergic Rhinitis (abbreviated as AR) refers to chronic inflammation in nasal mucosa induced by allergen. And this kind of chronic inflammation is mediated by IgE and participated by immunocyte and cytokines. The disease often causes many symptoms such as rhinostegnosis, rhinocnesmus, sneezing, and mucus in the nose and so on. AR now is a common disease in the world and recently the prevalence rate of AR is increasing year by year. And allergic asthma, sinusitis, rhinopolypus and tympanitis could be related with severe AR, which has caused serious effect in daily life, study and work to us. In Western Medicine, antihistaminics, decongestant drug, anticholinergics, mast cell stabilizer and corticosteroids are applied to the treatments of AR. However, there are many problems in these drugs such as the high relapse rate after treatments, side effects and expensive costs because of long-term treatments and so on. According to their clinical symptoms, AR could belong to "bi qiu", "qiu ti", "qiu shui", "qiu pen", "qiu", "pen" in Traditional Chinese Medicine (abbreviated as TCM). Recently, TCM researches of AR are increasing significantly. TCM treatments have accumulated rich experiences and achieved good effects, less side effects and lower recurrence under the supervision of TCM theories. TCM therapy has potential advantages and bright future in the treatment of AR, which has laid a good groundwork for the further study and the mechanism of TCM.Objective1 Putting the ancient literatures about AR in order, revealing the law and achievements in diagnosis and treatment of TCM, providing evidence for better treatment of TCM in AR.2 Discussing the relationship between AR and "Heat of lung and stomach, intestine" and feasibility of applying "clearing the heat of intestine and lung" to treat AR.3 Copying AR model of guinea pig, and applying the modern scientific and technological research methods to study the effect and mechanism of HQT modified extract drops on experimental guinea pig AR model, in order to provide experimental basis for prevention and treatment of AR.Method1 Theoretical StudyAccess to the ancient Chinese medical literatures, the discuss of "bi qiu", "qiu ti", "qiu shui", "qiu pen", "qiu", "pen" was put in order and the law of their diagnosis and treatment were revealed. And the feasibility of applying "clearing the heat of intestine and lung" to treat AR and explain the theoretical basis for the AR was well considered and discussed. 2 Experimental Study2.1 The copy and evaluate the guinea pig models of AR60 healthy guinea pigs were used to copy the guinea pigs models of AR though ovalbumin (OVA) sensitization. The experimental groups of guinea pigs were injected by a mixed suspension:ovalbumin (OVA) 30mg, Al(OH)330mg, and lml saline, one time two days for 7 times; inhalation of 0.5% OVA saline solution for 5 consecutive days, one time a day; 3 days later, nasaldrops with 2% OVA saline solution, one time a day for 4 days. Normal group used saline instead of OVA. The models were observed and evaluated through the changes of behavioral symptoms and of nasal mucosa (both macroscopic and microscopic).2.2 Pharmacodynamics Study and Mechanism Study of HQT Modified extract DropsAfter adaptive feeding one week,60 healthy guinea pigs were randomly divided into control group A, AR model group B, HQT Modified extract Drops low frequency group C, HQT Modified extract Drops middle frequency group D, HQT Modified extract Drops high frequency group E, ketotifen fumarate Drops positive control group F,10 guinea pigs in each group. A, B two groups were given intranasal 10μl saline, one time 2h; C group were given intranasal 10μl HQT Modified extract Drops, one time 6h; D group were given intranasal 10μl HQT Modified extract Drops, one time 4h; E group were given intranasal 10μl HQT Modified extract Drops, one time 2h, F group were given intranasal 10μl ketotifen fumarate, one time 2h. All the groups were administered for 3 weeks The activity, food and water intake, and spirit of guinea pigs were obseverd. The count of scratch nose, sneezing after administration in 5 min was recorded. After anaesthetized, all animals were sacrificed 24 hours after last administration. Peeling nasal mucosa off from nasal cavities and select the left nasal mucosa fixed in 4% neutral paraformaldehyde solution for 48h, and dehydration, clearing, paraffin, embedded, sliced, paraffin sections for HE staining. The other side of the nasal mucosa was put into liquid nitrogen to freeze and prepare for extraction of SP-R mRNA. The blood sample was drawn from abdominal aorta to be detected Histamine,IL-4, IL-5, TNF-a levels with a biochemical method. RT-PCR method was detected SP-R mRNA expression of nasal tissue.Results1 Theoretical ResearchIn the study of ancient literatures about AR, the location of the disease was founded in the nose, and "lung" and "stomach, intestine" are closely related to AR. The basic mechanism is that the heat of lung and stomach intestine steam up to the nose. With the improvement of living standard, the great wealth of material life, and life diet adjustment, more and more people prefer to have fatty and spicy food, tobacco and alcohol products, and this could make spleen and stomach stagnation, so heat and dampness produce. Heat and wet through the meridians could steam up to the nose lead to AR. So "clearing the lungs and gastrointestinal heat" as the basic principles. HQT treatment prescription could clear dampness and heat. And according to modern research, active ingredients of herbs in HQT prescription have a good anti-allergic effect. These could be the theoretical basis of its treatment of AR2 Experimental Research2.1 Model EvaluationThough the observation of OVA sensitization method to copy guinea pig AR model, the number of sneezing and nasal scratching compared with the control group was significantly increased (P<0.05); and allergic characteristic pathology syptom of rhinitis was appeared under the light microscope. OVA progressively sensitized guinea pigs lead to allergic rhinitis model was easy to copy, and model survival rate can reach 90%, and caused disease rate was 100%. Therefore this model should be the good rhinitis animal model.2.2 The effect of modified HQT extract drops on guinea pigs AR model.Compared with model group, the number of sneezing and nasal scratching in the treatment groups were significantly decreased (P<0.05). Modified HQT extract drops high, medium and low frequency groups can improve model of pathological tissue damage in nasal mucosa, and reduce inflammatory cell. Inflammatory cell score in light microscopy was significantly decreased compared with the model group (P<0.05)2.3 The influence of modified HQT extract drops on content in serum Histamine of the guinea pig animal AR modelThe content of serum Histamine in AR guinea pig model group was significantly increased compared with the normal group (P<0.001). Modified HQT extract drops (high, medium and low frequency) can significantly reduce serum Histamine content in guinea pig (P<0.001), in which high and middle frequency group was better than low frequency group. Middle frequency group had best effect in Histamine reduction.2.4 The influence of modified HQT extract drops on content in serum IL-4, IL-5 of the guinea pig animal AR modelThe content of serum IL-4, IL-5 in AR guinea pig model group was significantly increased compared with the normal group (P<0.001, P<0.01). Modified HQT extract drops (high, medium and low frequency) can significantly reduce serum Histamine content in guinea pig (P<0.001, P<0.01), which were better than ketotifen fumarate Drops positive control group.2.5 The influence of modified HQT extract drops on content in serum TNF-a of the guinea pig animal AR modelThe content of serum TNF-a in AR guinea pig model group was significantly increased compared with the normal group (P<0.001). Modified HQT extract drops (high, medium and low frequency) can significantly reduce serum TNF-a content in guinea pig (P<0.001), in which high and middle frequency group was better than low frequency group. Middle frequency group had best effect in TNF-a reduction.2.6 The influence of modified HQT extract drops on SP-R mRNA expression in nasal mucosa of the guinea pig animal AR modelThe expression of s SP-R mRNA in nasal mucosa of AR guinea pig model group was significantly increased compared with the normal group (P<0.001). Modified HQT extract drops (high, medium and low frequency) can significantly reduce SP-R mRNA expression in nasal mucosa (P<0.001), in which high and middle frequency group was better than low frequency group. Middle frequency group had best effect in SP-R mRNA expression reduction in nasal mucosa.Conclusion1 Mechanism of allergic rhinitis is characterized as heat, and clearing the lungs and gastrointestinal heat is the way to treat AR.2 OVA sensitization is an ideal method to establish the RE model.3 Significant morphological changes, such as the destruction of nasal epithelial cells, vascular congestion, glandular swelling, and infiltration of eosinophils could be observed in the nasal mucosa of AR animals.4 The followings could be the mechanism of modified HQT extract drops treating AR.4.1 Significantly decreasing the content of Histamine in serum.4.2 Significantly decreasing the content of IL-4,IL-5 in serum.4.3 Significantly decreasing the content of TNF-a in serum.4.4 Significantly decreasing the content of SP-R mRNA expression in nasal mucosa.In summary, modified HQT extract drops treat AR probably by regulating the immune and neural regulatory mechanisms to achieve the therapeutic effect; from TCM point of view, HQT treat AR though clearing the lungs and gastrointestinal heat. Modified HQT extract drops (high, medium and low frequency) have a significant effect on AR. Middle frequency group has best affect. |
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