| Studies have shown that intestinal flora is strongly associated with chronic metabolic diseases such as obesity,inflammation,and diabetes,and that there is an association between polycystic ovary syndrome(PCOS)and intestinal flora,but the direct effects of intestinal flora on these diseases are not yet clear,and the direct role of intestinal flora in producing or exacerbating metabolic disorders in these disease states has not been determined.Fecal microbiota transplantation(FMT)or fecal filtrate transplantation(FFT)can lead to a causal relationship between gut flora and host;cohabitation flora exchange studies have shown that cohabitation with healthy mice can prevent obesity and maternal high-fat diet-induced metabolic dysregulation.It is hypothesized that intestinal flora may play a key role in the development of metabolic disorders,including PCOS.PCOS is a common reproductive endocrine disease,and the relationship between inflammation and PCOS is a current research hotspot.Alpha1antitrypsin(A1AT)maintains the metabolic stability of the body by inhibiting the hydrolysis of proteases and acts as a stress response protein in vivo to suppress inflammation.There is a gap in elucidating the ameliorative effect of A1 AT on PCOS from the perspective of inflammation.In this study,we used dehydroepiandrosterone(DHEA)and letrozole-induced changes in intestinal flora and metabolomics in a PCOS mouse model to compare body weight,kinetic cycle,sex hormones,glucose tolerance and insulin tolerance,triglycerides(TG),total cholesterol(TC),tissue staining,immunohistochemistry and other assays to analyze the antiinflammatory effects of A1 AT and letrozole on PCOS mice.total cholesterol(TC),tissue staining,immunohistochemistry and other assays to analyze the modeling effect of dehydroepiandrosterone and letrozole and the intervention effect of A1 AT on PCOS mice,to clarify the anti-inflammatory effect of A1 AT,and to provide a new approach for the treatment of PCOS and other anti-inflammatory studies,the main results are as follows.1、Intervention effect of A1 AT in obese PCOS model mice on DHEA protocolIn terms of body weight,the body weight,tissue wet weight and liver index of mice in the three PCOS modeling groups(M1:high-fat diet modeling group,M2:dehydroepiandrosterone modeling group,M3:high-fat diet combined with DHEA modeling group)were significantly higher than those in the control group,and the body weight,tissue wet weight and liver index of mice in the M3 group were the largest,while the body weight,tissue wet weight and liver index of mice in the treatment group(T:A1AT intervention group)were significantly lower than those in the M3 group.In terms of estrous cycle and ovarian pathological analysis,the regularity of estrous cycle disappeared,the length of estrous cycle was prolonged,and the estrous period appeared to be persistent,and the pathological changes in ovarian structure were most significant in the M3 group,while the estrous cycle and ovarian polycystic-like changes were improved in the treated group;in terms of sex hormones,the sex hormone levels were significantly higher in the M3 group and lower in the treated group;the expression of A1 AT m RNA in the tissues of the mice in the M3 group was significantly lower than that in the M3 group.In terms of sex hormones,the expression of A1 AT m RNA in the tissues of mice in the M3 group was significantly lower,while the expression of A1 AT m RNA in the tissues of mice in the treatment group was significantly higher;in terms of glucose tolerance test and insulin tolerance test,mice in all three PCOS modeling groups showed significant abnormalities,while mice in the treatment group showed significant improvement in glucose tolerance and insulin tolerance;in conclusion,mice in the M3 group were more compatible with the requirements of polycystic ovary modeling,and the M3 group was set as the modeling group.In terms of intestinal flora,the flora structure of mice in the control,model and treatment groups were affected by the modeling and A1 AT interventions,and it was hypothesized that A1 AT could regulate the flora structure of PCOS mice and convert them to normal flora structure.2、Intervention effect of A1 AT on the Letrozole protocol in obese PCOS model miceIn terms of body weight,compared with the control group,the body weight of mice in the model and fecal fixation groups increased significantly,and compared with the model group,the body weight of mice in the fecal filtrate fixation and treatment groups decreased significantly;in terms of motility cycle and tissue analysis,the regularity of motility cycle of mice in the model and fecal fixation groups disappeared,and the tissue structure was pathologically changed,while the regularity of motility cycle of mice in the fecal filtrate fixation and treatment groups increased,and the tissue pathological changes were improved.In terms of the four lipids,the serum levels of TC,TG and LDL in the model and fecal fixation groups were significantly higher than those in the control group,and the HDL levels were significantly lower than those in the control group,while the serum levels of TC,TG and LDL in the fecal filtrate fixation and treatment groups were significantly lower than those in the model group,and the HDL levels were significantly higher than those in the model group.The expression of monocyte chemotactic protein-1 was significantly higher than that of the control group,while the expression of macrophage infiltration and monocyte chemotactic protein-1 was significantly lower in the mice of the fecal filtrate fixation and treatment groups.A1 AT could regulate the flora structure of PCOS mice and transform them to normal flora structure;the results of metabolomic analysis showed that the contents of colonic contents were higher in acetic acid,propionic acid and butyric acid,and the contents of isobutyric acid,isovaleric acid and hexanoic acid were extremely low;the contents of acetic acid and propionic acid in the colonic contents of mice in the model group were significantly higher than those in the control group,and the levels of the remaining five short-chain fatty acids were significantly lower than those in the control group.The levels of acetic acid and propionic acid in the colon of mice in the treatment group were significantly lower,and the levels of the remaining five short-chain fatty acids were significantly higher than those in the model group,and the levels of propionic acid,isobutyric acid,isovaleric acid,valeric acid and hexanoic acid were not different from those in the control group,indicating that A1 AT can significantly improve the levels of short-chain fatty acids in the colon of mice in the PCOS model,thus further interfering with the development process of PCOS. |
PDF Full Text Request