ABSTRACT
ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease（COPD）， and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups， including blank group， model group， fecal bacterial transplantation（FMT） group， dexamethasone group and low， medium and high dose groups of Bufeitang， 12 rats in each group. Except for the blank group， cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide（LPS） were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low， medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang（3.645， 7.29， 14.58 g·kg-1）， the FMT group was given fecal bacteria liquid enema（10 mL·kg-1）， dexamethasone group was given dexamethasone acetate tablet suspension by gavage（0.135 mg·kg-1）， the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin（HE） for pathomorphological observation， and enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in lung tissues. ResultCompared with the blank group， the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group， the extent of injury was significantly improved， and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group， the model group had severely abnormal colonic tissue structure， the epithelial cells in the mucosal layer were eroded and shed， the number of inflammatory cells increased， the submucosal layer was edematous and the gap was enlarged. Compared with the model group， the extent of damage was significantly improved in the medium and high dose groups of Bufeitang， the epithelial cells in the mucosal layer were neatly and closely arranged， with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group， the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased（P<0.01）. Compared with the model group， the TNF-α and IL-8 levels of lung tissues in the low， medium and high dose groups of Bufeitang were significantly decreased（P<0.01）. Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats， corrected the return of intestinal flora to normal abundance and diversity， and positively regulated 4 differential phyla（such as Firmicutes， Proteobacteria） and 13 differential genera（such as Turicibacter， Lactobacillus， Anaerobiospirillum， Intestinimonas） in COPD model rats with lung Qi-deficiency syndrome， and down-regulated 2 carbohydrate metabolic pathway functions， including the pentose phosphate pathway（non-oxidative branch） Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species， affect the function of metabolic pathways， repair the structure of lung and colon tissues， regulate the level of inflammatory factors， and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.
ABSTRACT
Background: Asthma and diabetes are both diseases that affect a wide range of people worldwide. As a common treatment for diabetes, metformin has also been reported to be effective in improving asthma outcomes. We conducted a combined analysis to examine the efficacy of metformin in reducing asthma exacerbation in patients with concurrent asthma and diabetes. Methods: We searched the PubMed, Embase, and CENTRAL databases for articles published prior to April 2020 to find observational studies of individuals with concurrent asthma and diabetes that compared the risk of asthma exacerbation between metformin users and nonusers. Two researchers separately screened the studies, extracted data, and evaluated the risk of bias. The primary outcome was the adjusted risk of asthma exacerbation. The secondary outcomes were the adjusted risk of asthma-related hospitalization and emergency room visits. Review Manager was used for data analysis and plotting. I 2 and χ 2 tests were used to estimate heterogeneity. A random effects or fixed effects model was used depending on the heterogeneity. Odds ratios were calculated for dichotomous variables. Results: We included two studies with a total of 25252 patients. The pooled effect size showed that metformin was inversely associated with a risk of asthma exacerbation (OR = 0.65, 95% CI 0.28-1.48; χ 2 = 5.42, P=0.02; I 2 = 82%), asthma-related emergency department visits (OR = 0.81, 95% CI 0.74-0.89; χ 2 = 0.36, P=0.55; I 2 = 0%), and hospitalizations (OR = 0.43, 95% CI 0.14-1.29; χ 2 = 4.01, P=0.05; I 2 = 75%). Conclusion: This meta-analysis suggested that metformin decreased the risk of asthma-related emergency room visits for patients with concurrent asthma and diabetes. Metformin reduced the risk of asthma-related hospitalization and exacerbation but was not statistically significant. More randomized trials involving larger samples should be considered, and the mechanisms of these effects need to be fully elucidated.
