Multiple Organ Injury Induced By Cigarette Smoke In Tree Shrews

It is well know that cigarette smoking(CS)is a major risk factor for heart,lung,liver and kidney cancer and organ dysfunction.Rodent is mostly used as animal model.However,these models do not accurately reflect the true figure because their pulmonary anatomical structure and immune system are not comparable to those of humans.Non-human primate’s models are similar to humans in terms of genetics,anatomy,and physiology,but they are very expensive.Tree shrews are primate close relatives,its nervous and immune systems are high degree of homology with human,in many ways can be used to replace non-primate experimental animals.The aim o f this study was to introduce tree shrew as a potential animal model for investigating the effect of tobacco smoking on lung,liver,kidney,and heart.We evaluated the organ pathologies and functional variation by using histopathological analyses and behavioral observation.A total of 24 adult Chinese tree shrews(Tupaiabelangerichinensis)were obtained and divided into two groups: trea tment group(n=18)and control group(n=6).Both groups for exposed to air or cigarette smoke for 30 min,twice a day,6 days per week for up to 9 months.In order to evaluated the effect of cigarette smoke exposure on the behavior of tree shrews,in the study three shrews were observed and recorded in real time.The result showed that CS exposed groups were closed their eye;mouth was slightly open with unconscious drooling,head placed on their back on the vertical pos ition,shortness of breath.Among these signs,drooling,head placed on their back,mouth open and shortness of breath was significantly increased with the increase of smoking period,as compared with the control group.In this study we examined the deposition of nicotine in organs by LC-MS/MS so as to detect the smoking capacity of heart,liver,kidney,lung in tree shrews.It was found that the deposition of nicotine in the heart,liver,kidney and lung increased gradually with the increase of cigarette smoke exposure time.To analyze the effect of cigarette smoke exposure on the histological structure of heart,liver,kidney and lung,the histological structure of each organ was observed by HE staining.Tree shrew in the control group exhibited normal appearance,with well-define histological structure without any mark of abnormality.However,the histopathologic analysis of CS-exposed organ has showed distinct s ign of lesions,such as parenchymal lesions in alveolar space of lungs;a dot-like necrosis and inflammatory cell infiltration in the hepatocyte,renal tubular epithelial cell inflammation and degeneration,cardiac hypertrophy and hyper-chromatic in heart tissue.To study the occurrence of cigarette smoke exposure to heart,liver,kidney and lung in tree shrews,the degree of fibrosis of each organ was observed by Masson staining.We found that tree shrews treated by cigarette smoke exposure showed an increase in fiber,while the different organs of the changes in the trend and varying degrees.In order to further analyze the effects of cigarette smoke exposure on visceral function of heart,liver,kidney and lung tissue,the mucous secretions of lungs were examined by PAS staining and the expression of macrophages in lung and the expression of apoptosis in viscera were measured by immunohistochemical staining.The result showed that the mucus secretion of the tree shrew exposed to cigarette smoke did not change significantly with the control group,as well as the number of macrophages and apoptotic cells showed a decrease in the lungs in cigarette smoke exposure.Conversely,the number of apoptotic cells in the heart,liver and kidney of the tree shrew exposed to cigarette smoke increased.Current study results demonstrated that CS-exposed tree shrews have shown similar morphological and pathological characteristics with humans.Therefore,CS-exposed tree shrews can provide a useful way to establish as animal model of studying the pathogenesis of the smoking and for evaluation of drug effectiveness.