Study On Lung And Intestinal Injury And Changes Of Gut Microbiota Caused By Cigarette Mainstream Smoke And The Mechanism

Cigarette mainstream smoke is the smoke inhaled from the filter end when smoking with complex components that seriously threaten the health of smokers.The study investigated the effects of cigarette mainstream smoke on the lung and intestine of mice and explored the related mechanisms by establishing the exposure model of cigarette mainstream smoke and its components(PM_2.5 and nicotine)in mice to provide new ideas for physical health care and injury intervention for smokers.C57BL/6 mice were randomly divided into four groups（n=10）:control group（C）,cigarette mainstream smoke nicotine exposure group（Nicotine）,cigarette mainstream smoke PM_2.5 exposure group(PM_2.5)and cigarette mainstream smoke exposure group（CMS）to establish a model of exposure to cigarette mainstream smoke and its components and to study the effects of cigarette mainstream smoke on lung,colonic tissue and intestinal microbiota.After that,the mechanism of CMS-mediated lung and intestinal injury and intestinal microbiota alteration was further investigated by inhibiting the activation of nuclear transcription factorκB（NFκB）.The main findings of this study are as follows:I.Cigarette mainstream smoke causes lung and intestinal injury and changes of gut microbiota1.Cigarette mainstream smoke and its components(PM_2.5 and nicotine)caused lung inflammatory,oxidative and apoptotic damage in mice by regulating the expression of inflammatory factors（IL-1β,IL-6 and TNF-α）and inflammation-related proteins（My D88,p-NFκB/NFκB and TLR4）,oxidative factors（MDA,SOD and GSH）and apoptosis-related proteins（Bax/Bcl-2,Cleaved caspase 3）.2.Cigarette mainstream smoke and its components(PM_2.5 and nicotine)caused intestinal injury and changes of gut microbiota in mice with reduced Firmicutes and increased Bacteroidetes;reduced beneficial bacteria（Lactobacillus and Akkermansia）and increased harmful bacteria（Helicobacter）.II.CMS mediates lung and intestinal injury and changes of gut microbiota via NFκB pathway and lung-gut axis1.By inhibiting NFκB activation,the high expression of pulmonary pro-inflammatory factors（IL-1β,IL-6 and TNF-α）,oxidative factors（MDA）and apoptosis-related proteins（Bax/Bcl-2 and Cleaved caspase 3）decreased and reduced antioxidant factors（SOD and GSH）increased caused by cigarette mainstream smoke,effectively alleviating the cigarette mainstream smoke-mediated lung injury.2.There is a potential mechanism of lung-gut axis between lung injury and intestine,and the degree of lung injury is positively correlated with the degree of intestinal injury and changes of gut microbiota.When mice were exposed to cigarette mainstream smoke,lung injury appeared,accompanied by intestinal damage,increased intestinal permeability and reduced gut microbiota diversity,with fewer beneficial and more harmful bacteria;by inhibiting NFκB activation,the lung damage caused by cigarette smoke was alleviated,and intestinal damage was also alleviated,the changes of gut microbiota were reduced and approached to normal mouse gut microbiota.