Experimental Research On The Treatment Of Silicosis In Dogs By Intelligent Lung Lavage Machine

Background:Silicosis is a chronic occupational disease characterized by pulmonary fibrosis andpulmonary inflammation, due to long-term inhalation of high concentrations of freesilica(SiO2) dust in the production process. Pneumoconiosis is the most seriousoccupational diseases currently in China, and silicosis accounted for a large proportion ofthem, which caused direct economic losses of billions of dollars every year, and a heavyburden to individuals, families, businesses, and society.Researches have confirmed that alveolar macrophage cells are the most importantinflammatory cells in the formation of silicosis, which can devour the silica dust, secret andrelease a large number of inflammatory factors causing activation and fibrosis, TGF-beta isrecognized as a critical cytokine during the development of the pulmonary fibrosis. Lungfibrosis is also the result of uneven synthesis and degradation of extracellularmatrix(ECM)and matrix metalloproteinases(MMPs) plays a very important role. After theactivation, alveolar macrophages release cytokines and inflammatory mediators which playa major role in the early lung injury, and the remaining dusts in lung would continuallyactivate the alveolar macrophage, which is the main cause of the progress of the diseasewhen people get out of the environment full of dust.So far there is no effective treatment for Silicosis and the common therapies includelung lavage, medicine and traditional Chinese medicine. Treatment with medicine is notvery effective but whole lung lavage (WLL)is a more effective treatment strategy. Thetraditional lung filling wash treatment relies on artificial means for gravity filling liquid andpumping liquid, and there has no specific wash lung instrument for Standard operation andmonitoring. The shortages are relative complex operation, taking long low efficiency,unstable filling wash velocity and the pressure, inconstant temperature of filling washliquid, no real-time data during monitoring and more complications, which needs to be resolved. In order to alleviate the suffering of patients with pneumoconiosis and make lunglavage operation more standardized and efficient, we combined our own understanding oflung lavage technique with modern electronic software programming techniques, andsuccessfully developed an lung lavage machine, in order to apply it to clinical treatment ofsilicosis. In order to verify the safety and effectiveness of smart lung washing machine, wehave designed this experiment and applied it to the canine model of silicosis, the result ofwhich would provid fundamental theoretical basis for the conduct of clinical trials in thefuture.Objective:1. To simulate dust exposure and pathogenic processes of silicosis, establish canineanimal model of silicosis and observe the changes of canine chest CT Imaging andpathologies in lung tissue.2. Application of traditional and intelligent lung lavage in the treatment for silicosis indogs, observe the expression of TGF-beta1, MMP-2, MMP-9, cytokines in alveolarmacrophages of dogs, and explore the significance of changes.3. Preliminary assessment of safety and effectiveness for intelligent lung lavage in thetreatment of silicosis in dogs.Methods:1. The establishment and assessment of a canine model of silicosis.Twenty healthy hybrid dogs are randomly divided into4groups: healthy control group,low doses and low frequency group, high doses and low frequency group, and high dosesand high frequency group. Different dust-exposed to dose and frequency, different timeperiods, arterial blood gases, chest CT Imaging and pathological changes of lung tissue areobserved, in order to, explore the method of establishing canine animal model of silicosis.2. The assessment of safety and effectiveness for intelligent lung lavage in thetreatment of silicosis in dogs.Ten local health hybrid dogs are randomly divided into2groups: traditional lunglavage in the control group and intelligent lung lavage in the control group. Ten silicoticdogs are randomly divided into2groups: traditional lung lavage group and intelligent lunglavage group. Each group of dogs are treated with the corresponding method of lung lavageand the results of traditional and intelligent lung lavage are compared. The survival rate of experimental dogs, arterial blood gases before and after lavage lavage, fluid recovery rate,and the chest CT Imaging findings are compared, in order to assess the security of anintelligent canine lung lavage in the treatment of silicosis. The lavage operation time, totalnumber of cells and classification of lavage recovery fluid, irrigation fluid recycling dustremoval, and lavage liquid AM culture TGF-of the Qing dynasty, such as Beta1, MMP-2,MMP-9, are investigated, in order to assess the effectiveness of intelligent lung lavage inthe treatment of dogs with silicosis.Results:1. After exposing to dust in each group of canines, there are different degrees ofpulmonary hyaline change of grinding and lung texture augmentation in CT pulmonarywindow, and the more dust-exposed dose, the higher frequency, and the longer time, themore obvious are the chest CT changes,.2. Long tissue specimens are taken after3months of Canines exposed to dust, andobserved under the light microscope. There are bronchial macrophage accumulation arounda lot of swallowing dust, fibroblast proliferation and collagen fiber mesh formation,pulmonary interstitial thickening. There are thickening of interstitial lung with a largenumber of free silica particle deposition under polarizing microscope. The bigger dose ofsilicotic dust and the higher frequency, the more evident are the pathological changes oflung tissue.3. The average time of unilateral lung lavage is35.7±2.3min with intelligent lunglavage and the average time is43.6±2.9min with artificial traditional lung lavages. Thedifference of average time between two groups is significant (P<0.01), which shows thatthe smart lung lavage can reduce the lung lavage operation time.4. The survival rate of experimental canine in the intelligent lung lavage group is100%and the rate of lavage liquid recovery is88.9±1.6%; while the survival rate in thetraditional lung lavage group is90%and the rate of lavage liquid recovery is85.7±1.7%.Chest CT shows the lung lavage liquid has been totally absorbed after7days of the lavageand the lungs recruited well, which suggested that the security of intelligent lung lavage isnot less than that of traditional lung lavage.5. The filling wash recovery liquid of dust volume and liquid volume of ratio is1.31±0.08g/L with intelligent lung lavage, filling wash recovery liquid of cell number is343.53± 99.04x106, single nuclear giant GM cell of classification is90.2±1.6%, filling washrecovery liquid of alveolar macrophage cell supernatant TGF-beta1concentration is0.75±0.12ng/ml, MMP-2concentration in the supernatant is346.76±11.07ng/ml, and MMP-9concentration in the supernatant is21.94±6.01ng/ml. Compared with the healthy controlgroup, the differences are significant (P<0.01), which shows that effectiveness withintelligent lung lavage is not less than the traditional lung lavage.Conclusions:1. Canine model of silicosis can be established with the silica dust blowing into thelungs through ventilators ventilation after endotracheal intubation and the dose of the silicadust is,400mg/kg each time, once a week for3months.2. This study preliminarily verificated the security of intelligent lung lavage in thetreatment of silicosis in canine, and the security of intelligent lung lavage is not less thantraditional lung lavage.3. Dust of silicon dioxide, inflammatory cells and cytokines depositing in the lung ofcanine with silicosis can be effectively removed by intelligent lung lavage machine, so as toprevent and delay the progression of silicosis, which suggested effectiveness withintelligent lung lavage is not less than the traditional lung lavage.4. Intelligent lung lavage machine makes lung lavage operation proceduresprogrammed, intelligent and efficient. The operation time of lung lavage can be reduced bythe intelligent lung lavage machine and this machine can monitor the real time data, such aslavage fluid temperature, pressure and flow speed, which greatly reduced the amount ofartificial lung lavage operation.