Résumé
OBJECTIVE To explore the mechanism of Tingli dazao xiefei decoction on ventricular remodeling in model rats with heart failure after myocardial infarction. METHODS The rat model of heart failure after myocardial infarction was established by ligation of anterior descending branch of left coronary artery， which was divided into 8 groups： sham operation group， model group， A779 group （1 mg/kg）， A779 （1 mg/kg）+Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， A779 （1 mg/kg） +Tingli dazao xiefei decoction high-dose group （1.6 g/kg）， Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， Tingli dazao xiefei decoction high-dose group （1.6 g/kg） and losartan potassium group （10 mg/kg）. Each group was given equal volume of distilled water or corresponding drugs intragastrically for 4 weeks. Masson staining was used to determine the distribution of collagen fibers in rat myocardium. The content of hydroxyproline （Hyp） in myocardium was determined by alkaline hydrolyzation. The expressions of type Ⅰ and Ⅲ collagen （COLⅠ， COLⅢ）in myocardium were detected by immunohisto-chemistry. Myocardial fibrosis-related indexes such as matrix metalloproteinase-2 （MMP-2）， MMP-9， tissue inhibitor of metalloproteinase-1 （TIMP-1） and soluble suppression of tumorigenicity-2 （sST-2） were detected by ELISA. The protein expressions of angiotensin converting enzyme 2-angiotensin-（1-7）-Mas [ACE2-Ang-（1-7）-Mas] axis were detected by Western blot. RESULTS Compared with sham operation group， myocardial cells in model group and A779 group were disordered， collagen fiber deposition was significantly increased and myocardial fibrosis was obvious； the Hyp content and MMP-2， MMP-9， sST-2 levels were increased， and COL Ⅰ and COL Ⅲ positive expressions were significantly enhanced； TIMP-1 level， protein expressions of ACE2， Ang-（1-7） and Mas were significantly decreased （P＜0.05）. Compared with model group， above indexes of Tingli dazao xiefei decoction equivalent-dose and high-dose groups were improved to different extents. Compared with A779 group， A779+Tingli dazao xiefei decoction equivalent-dose and A779+high-dose groups could improve myocardial arrangement and collagen distribution， reduce the Hyp content and MMP-2， MMP-9 levels， reduce positive expressions of COL Ⅰ and COL Ⅲ （P＜0.05）， but couldn’t improve Ang-（1-7） and Mas protein expression. CONCLUSIONS Tingli dazao xiefei decoction can improve ventricular remodeling in myocardial failure model rats after myocardial infarction by improving the expression of ACE2- Ang（- 1-7）-Mas axis proteins.
Résumé
The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.
Résumé
Objective:To evaluate the clinical efficacy of Buyang-Huanwu Decoction combined with modified Tingli-Dazao-Xiefei Decoction on the basis of conventional western medicine therapy in the treatment of chronic heart failure (CHF) with syndrome of qi deficiency and blood stasis. Methods:Seventy patients who met the inclusion criteria from November 2017 to November 2019 in Shijingshan District Hospital of Traditional Chinese Medicine were randomly divided into two groups, 35 in each group. The control group was treated with western medicine for chronic heart failure, and the treatment group was treated with Buyang-Huanwu Decoction combined with Tingli-Dazao-Xiefei Decoction on the basis of the control group. Both groups were treated for 2 weeks. The TCM syndrome scores were observed and compared before and after treatment. Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to evaluate the quality of life of patients. Lee’s Heart Failure Score was used to evaluate the severity of symptoms. The N-terminal pro-B type natriuretic peptide(NT-proBNP) was detected by ELISA. The adverse reactions during treatment were observed and the clinical efficacy was evaluated. Results:The total effective rate was 91.4% (32/35) in the treatment group and 77.1 % (27/35) in the control group, and the difference was statistically significant ( χ2=7.050, P=0.014). After treatment, the serum NT-proBNP in the treatment group [(1 725.3 ± 1 473.8) ng/L vs. (2 485.7 ± 2 164.4) ng/L; U=341.200, P=0.031] was significantly lower than that of the control group. The NT-proBNP [(54.3 ± 26.7) % vs. (35.5 ± 19.8)%; U=4.310, P=0.003] was significantly higher than that of the control group. After treatment, the TCM syndrome scores and MLHFQ scores in the treatment group were significantly lower than those in the control group ( t=3.785, 9.925, P=0.031, 0.001). During the treatment, no obvious adverse reactions were observed in both groups. Conclusion:On the basis of standardized treatment of Western medicine, Buyang-Huanwu Decoction and Tingli-Dazao-Xiefei Decoction can improve the clinical efficacy of CHF patients with qi deficiency and blood stasis syndrome, promote the repair of damaged myocardium (reduce NT-proBNP), and improve the quality of life of patients.