ABSTRACT
OBJECTIVE：To study the mecha nism of Bambuterol hydrochloride in the improvement of chronic obstructive pulmonary disease （COPD）model rats ，and to find the potential biomarker. METHODS ：Totally 30 rats were randomly divided into normal group ，model group and bambuterol hydrochloride group （3.3 mg/kg），with 10 rats in each group ；COPD model was established by lipopolysaccharide （LPS）infusion combined with smoking in model group and bambuterol hydrochloride group. After modeling ，bambuterol hydrochloride group was given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 45 d. After last medication ，the serum sample and alveolar lavage fluid of rats were collected. The levels of interleukin- 6（IL-6）and tumor necrosis factor-α（TNF-α）in alveolar lavage fluid were detected by ELISA. The serum metabolites were detected by LC-MS and analyzed by metabolomics. Orthogonal partial least squares discriminant analysis （OPLS-DA）was used to screen out the differential metabolites. The potential biomarkers were identified based on the related literature ，and the metabolic pathway enrichment analysis was carried out by MetPA analysis platform. RESULTS ：Compared with normal group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were increased significantly in model group （P＜0.05）. Compared with model group ，the levels of IL- 6 and TNF-α in alveolar lavage fluid of rats were decreased significantly in bambuterol hydrochloride group （P＜0.05）. Results of metabolomics and OPLS-DA showed that 21 differential metabolites and 12 potential biomarkers were found （including maleylpyruvate ， hydroxypyruvate， tartronate semialdehyde，etc.）. Bambuterol hydrochloride can significantly reduce the levels of maleylpyruvate ，methylselenocysteine and 5-deoxy-D-glucuronic acid （P＜0.05）， while increase the levels of hydroxypyruvate ， tartronate semialdehyde and. These biomarkers were mainly @163.com concentrated in pentose phosphoric acid pathway ，glyoxyli acid and tricarboxylic acid metabolism pathway ，followed by 开发。E-mail：pn333@163.com inositol phosphoric acid metabolism pathway ，arginine and tyrosine metabolism pathway ，glycine，serine and threonine metabolism pathway. CONCLUSIONS ：The mechanism of bambuterol hydrochloride improving COPD may be associated with the decrease of the levels of TNF-α and IL-6，as well as the pathway of amino acid metabolism ，energy metabolism and lipid metabolism.
ABSTRACT
This paper elaborated the research progress on transduction mechanisms of obese polycystic ovary syndrome (PCOS) and insulin resistance (IR). The action mechanisms of kidney-tonifying, spleen-invigorating and phlegm-resolving in the treatment of obese PCOS and IR were explored. It provided new ideas for the treatment of obese PCOS patients in the clinical practice of traditional Chinese medicine (TCM) gynecology. Literatures on TCM theories and modern signal pathways were used in the analysis of spleen-kidney deficiency and phlegm-dampness retention, which were the key pathogenesis of obese PCOS and IR. The scientific nature of treating obese PCOS and IR from the method of kidney-tonifying, spleen-invigorating and phlegm-resolving was demonstrated. The results showed that the scientific nature of treating obese PCOS and IR from the method of kidney-tonifying, spleen-invigorating and phlegm-resolving was initially demonstrated by the organic combination of TCM and modern medicine theories. It innovatively proposed that the treatment study strategy of transduction molecular mechanism took the interactive dialogue between PI-3K/Akt signal pathway and TNF-α signal pathway as its target. The regulatory role and action mechanism of this method in the treatment of obese PCOS and IR were discussed.