Clkc1 Treatment Of Children With Upper Respiratory Tract Infection Cough Pharmacodynamics And Mechanism

Pediatric coughing after upper respiratory tract infection refers to the children's coughing for a long time without healing while the cold restores, which is also called cough post infection, referred to as CPI. The upper respiratory tract infection is a common pediatric disease, frequently happens in winter, often leads to the post infection cough. For parts of the patients, respiratory symptoms of cough appear after the recovery of upper respiratory tract infection, lasting for several weeks to mohths, often misdiagnosed as bronchitis or pneumonia, and the repeated use of antibiotics, cough killer etc is of no effect. It not only brings the children of pain, but also causes economic burden for parents. Because of the high incidence of coughing after upper respiratory tract infection, the drug therapy has been more concerned in recent years.At present, the therapic drugs of CPI are mainly histamine receptor antagonist, central antitussive, anaesthetic, hormone, epinephrine never receptor antagonist, etc. Western medicine is not of great good effects in treating pediatric CPI. In treating cough, TCM has a long history and rich experience, our national unique traditional Chinese medicine resourse has provided a vast space for the application of TCM in treating CPI. Chinese patent medicines is convenient to carry and easy to use, so making Chinese prescription develope into Chinese patent medicines will have broad economic and social benefit based on the remarkable curative effect in treating CPI.CLKC1 is developed from experienced prescription. The function is lung-clearing and expectorant, antitussive and throat-clearing. It has been made into granules by pharmaceutical department of Beijing University of Chinese Medicine, using for the treatment of CPI.Generally speaking the main pathogenesis of CPI is AHR.With the function basis of CLKC1, combining the western medicine pathogenesis of CPI,we study pharmacological effect and function mechanism by conventional animal models. Two parts are mainly included:first a study on pharmacological effect; second the study on function mechanism. We try to clarify the function mechanism of CLKC1's pharmacological effect, in order to provide sufficient experimental data for the clinical using and new drug's application.1 Study on pharmacodynamics of CLKC1 in CPI treatment1.1 Study on antitussive effects of CLKC1Objective:To observe the antitussive effects of CLKC1. Methods:Antitussive effects were observed through mice cough test induced by SO2steaming and through guinea pigs cough test induced by citric acid. Results:CLKC1 decreased the frequency of mice cough induced by ammonia and guinea pigs cough induced by citric acid, prolonged the cough latent period,dose groups have good concentration response relations (p<0.05). Conclusion: CLKC1 shows certain Antitussive effects.1.2 Study on expectorant effects of CLKC1Objective:To observe expectorant effect of CLKC1. Methods:Expectorant effectswere evaluated by measuring the excretion of phenol red in mice trachea. Results: Increased the excretion of phenol red from mice trachea, promoted the movement of prepared Chinese ink in the mice trachea (p<0.05). Conclusion:CLKC1 shows certain expectorant effects.1.3 Study on Antiasthmatic effects of CLKC1Objective:To observe antiasthmatic effect of CLKC1. Methods:Antiasthmatic actions in guinea pigs were observed by histamine and acetylcholine ultrasonic atomization test. Results:CLKC1 can inhibited the guinea pigs asthma introduced by histamine and acetylcholine solution (p<0.05). Conclusion:CLKC1 shows certain antiasthmatic effects. 1.4 Study on bowel propulsion effects of CLKC1Objective:To observe the effect of CLKC1 on bowel propulsion in mice. Methods: Comput and compare the EB propulsion percentages in bowel in CLKC1 group, model group (treated with bowel propulsion supp ressants) and blank group, and the data were analyzed statistically 1. Results:CLKC1 dose groups could significantly increase EB propulsion percentages in mice(p<0.01).Conclusion:CLKC1 can promote intestine propulsive movement.1.5 Study on anti-inflammatory effects of CLKC1Objective:To observe anti-inflammatory effects of CLKC1. Methods:anti-inflammatory effects were observed by the swelling of hind paw in rats induced by carrageenin and granuloma induced by cotton pellets in rats. Results:CLKC1 medium and small doses groups can inhibite the paw edema induced by carrageenin (p<0.01), but not the granuloma induced by cotton pellet in SD rats. Conclusion:CLKC1 can inhibite early inflammation but without anti-inflammatory effects on later inflammation.2 Study on Function mechanism of CLKC1 in CPI treatment2.1 Study on effect of CLKC1 on AHR in allergic asthma rats Objective:To investigate the effects of CLKC1 on the inhibition of airway hyperresponsiveness(AHR) in allergen induced asthma in rats. Methods:Model group and CLKC1 group were challenged with ovalbumin (OVA) to reproduce asthma., the blank group only receied an injection of same amount of Al(OH)3. On the 22nd day determine airway resistance, the content of HMGB-1,IgE,IL-4,IL-13 in lung homogenate. Results: CLKC1 can reduce the rat airway resistance, and inhibit the content's increase of HMGB-1,IgE,IL-13,IL-4 in lung homogenate(P<0.05). Conclusion:CLKC1 can reduce airway resistance and inhibit AHR.2.2 Study on effect of CLKC1 on AHR of chronic asthma murineObjective:To investigate the effects of CLKC1 on the inhibition of airway hyperresponsiveness(AHR) in allergen induced asthma in Balb/c rats. Methods:model group and CLKC1 group were challenged with ovalbumin (OVA) to reproduce asthma.,the blank group only receied an injection of same amount of Al(OH)3 On the 22nd day determine the threshold of capsaicin cough sensitivity test, the content of NO,ET-1,IL-4,IL-13 in lung homogenate and their physiological and pathological changes. Results:CLKC1 can increase the threshold of capsaicin cough sensitivity test, inhibit the content's increase of lung homogenate's NO,ET-1,IL-4,IL-13(P<0.05). Conclusion:CLKC1 can inhibit AHR.2.3 Study on effect of CLKC1 on serum HMGB-1 level of sepsis micObjective:To observe the effects of CLKC1 on HMGB-1 protein expression in lung tissues of mice with endotoxin shock. Methods:Except the blank group, all other groups are injected LPS (5mg/kg)by the tails vein to establish the lung tissue injury models, The blank group only receied an injection of same amount of saline. Testing the serum HMGB-1 level at 24h,36h,48h,72h,96h. Study the effect of CLKC1 on serum HMGB-1 level of sepsis mic at the point of 72h. Results:72h after tail vail injection of LPS, serum HMGB-1 gets to the highest level; CLKC1 can inhibit the content's increase of HMGB-1 (P<0.05). Conclusion: CLKC1 can decrease serum HMGB-1 level.Conclusion1 The pharmacodynamics study shows that CLKC1 has antitussive, expectorant, antiasthmatic, bowel propulsion, anti-inflammatory effect pharmacological activity.2 Study on function mechanism of CLKC1 in treating coughing after pediatric upper respiratory tract infection indicates that CLKC1 can reduce airway resistance, inhibit the content's increase of inflammatory mediators and cytokines, promote airway remodeling so as to decrease AHR. Innovation1 First studied the effect of Chinese medicine granule on the expression of. terminal inflammatory mediators HMGB-1.2 Combine capsaicin cough sensitivity test with AHR animal models for the first time, detecting airway resistance by the threshold of capsaicin, and also study the effect of Chinese medicine granule on the threshold of capsaicin.