Mechanism of Qishen Decoction inhibition of macrophage M1 type polarization by targeting TGR5-mediated NLRP3 inflammasome

Objective:To observe the effect of Qishen decoction on TGR5-mediated activation of NLRP3 inflammasome,so as to clarify the molecular mechanism of its inhibition of macrophage M1-type polarisation to ameliorate non-alcoholic steatohepatitis;Methods:Mouse macrophage cell line RAW264.7 was randomly divided into a control group,model group,Qishen decoction group,TGR5 agonist group and Qishen decoction+TGR5 agonist group.Except for the control group,the remaining groups were constructed the macrophage NLRP3 activation model by palmitic acid induction,and the corresponding drugs were given to intervene.ELISA was used to detect the levels of TNF-α,IL-6,IL-1βand CXCL2 in macrophage supernatants,flow cytometry was used to detect the expression levels of macrophage polarisation marker molecules CD86 and iNOS,and Western blot was used to detect the expression of the TGR5/STAT1/STAT6 signaling pathway and the expression of NLRP3 inflammasome-associated proteins,respectively.Results:Compared with the control group,the contents of macrophages TNF-α,IL-6,IL-1β,CXCL2 and the proportion of macrophages with positive expression of CD86 and iNOS were significantly increased in the model group,and the differences were all statistically significant(P<0.01).Compared with the model group,the contents of TNF-α,IL-6,IL-1β,CXCL2 and the proportion of macrophages with positive expression of CD86 and iNOS were significantly decreased in the Qishen decoction group,and the differences were all statistically significant(P<0.01).In addition,the expression of NLRP3 and Pro-IL-1βproteins in the macrophage lysate and the expression of Caspase-1 p10,Caspase-1 p20 and IL-1βp17 proteins in the cell supernatant of the model group were significantly increased when compared with the control group,and the differences were all statistically significant(P<0.01).Compared with the model group,the expression of NLRP3 and Pro-IL-1βproteins in macrophage lysate and the expression of Caspase-1 p10,Caspase-1 p20 and IL-1βp17 proteins in cell supernatant of the Qishen decoction were significantly reduced,and the differences were all statistically significant(P<0.01);Conclusion:Qishen decoction can inhibit the activation of NLRP3 inflammasome in macrophages by inhibiting the TGR5/STAT1/STAT6 signaling pathway,thereby inhibiting macrophage M1 polarization and improving inflammatory response.

Exploration of the molecular mechanism of Qishen decoction in regulating miR-495/FTO pathway mediated macrophage polarization to improve insulin resistance therapy of type 2 diabetes

Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.

Qishen capsule safely boosts cardiac function and angiogenesis via the MEK/ERK pathway in a rat myocardial infarction model

Background Qishen(QS) capsules, a Traditional Chinese Medicine, has been widely used to treat coronary heart disease in China. However, evidence of its effectiveness remains unclear. Methods To explore whether QS has cardioprotective efficacy and/or promotes angiogenesis after myocardial infarction (MI), we performed experiments in a preclinical rat MI model. One month after left anterior descending coronary artery ligation, the rats received either QS solution (0.4 g/kg/day) or the same volume of saline by intragastric injection for four weeks. Results Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in MI rats administered QS. Indeed, QS treatment was associated with reduced infarct scar size and heart weight index, and these beneficial effects were responsible for enhancing angiogenesis. Mechanistically, QS treatment increased phosphorylation of protein kinase B (Akt) and downregulated phosphorylation of mitogen-activated protein kinase/extracellular-regulated kinase (MEK/ERK). Conclusions QS therapy can improve the cardiac function of rats after MI by an underlying mechanism involving increased angiogenesis, at least partially via activation of the Akt signaling pathway and inhibition of MEK/ERK phosphorylation.

Effect of Qishen Yiqi dripping pills combined with trimetazidine on the treatment of chronic heart failure: A meta-analysis

Objective:To systematically evaluate the safety and effectiveness of Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure.Methods:A total of four English and Chinese electronic databases were searched:CNKI,VIP,CBM,PUBMED.Cochrane bias risk tools were used to assess the methodological quality of qualified studies.Meta-analysis was conducted by Review Manager 5.3.A total of 9 articles were included,with a total sample size of 855 cases,443 cases in the observation group and 412 cases in the treatment group.Results:Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure has a total effective rate(RR=1.22,95%CI[1.15-1.30];p<0.00001),LVEF(MD=6.03,95%CI[5.39,6.67],P<0.00001),BNP(MD=-101.87,95%CI[-109.90,-93.83],P<0.00001),E/A(MD=-4.32,95%CI[-5.70,-2.93],P<0.00001),SYP(MD=-10.32,95%CI[-13.32,-7.32],P<0.00001),LVESD(MD=-5.50,95%CI[-6.03,-4.96],P<0.00001),6-MWT(MD=110.13,95%CI[96.89,123.36],P<0.00001)Adverse reactions occurred less frequently and did not affect treatment.Conclusion:This study shows that QYDP combined with TMZ can improve various indicators of CHF patients.However,due to the small sample size and the generally low quality of research,a more rigorous and reasonably designed RCT is needed to confirm these findings.

Effects of Qishen Ultrafine Powder on Immune Efficacy in Chickens

[Objective] This paper aimed to observe the effects of Qishen ultrafine powder on immune efficacy of infectious bursal disease vaccine in chickens. [ Method] 360 1-day-old chickens were randomly divided into six groups equally, and group I -V were vaccinated with IBD live virus vaccine on the 21 th and 35th day, respectively. From 14th to 21th day, group I - Ⅲ were added with 1%, 0.5% of Qishen ultrafine powder and 2% of Qishan powder in basel diet, respectively, group IV was given Yupingfeng oral liquid and group VI was as a control group without vaccination. Be- fore the expedment （14-day-old chickens as DO ） and 7 （ D7 ）, 14 （ D14 ）, 21 （ D21 ）, 28 （ D26 ）, 35 （ D36 ）, 42 （ D42 ） days after the experiment, the dynamic change of serum IBD specific antibody was determined, respectively. On D7, D21 and D36, the dynamic change of peripheral T lymphocyte proliferation and IL-2 in serum were determined, respectively. The weight change was also observed. [Results] Compared with the immune control group, the immune effects of IBD vaccine of each administration group were significantly improved, and there was no significant difference between each other. [ Condusion] Qishen ultrafine powder could increase immune function of chickens at lower dosage.

Medicated Serum of Qishen Yiqi Pill Affect Vascular Smooth Muscle Cell Proliferation,Cell Cycle,Cyclin D1 and CDK4 Mechanism Research

Observation of stilbene dropping pill and yiqi drug-containing serum influence mechanism of vascular smooth muscle proliferation， cell cycle and Cyclin D1 and CDK4Choose male SD rats were randomly divided into 2 groups， lavage qishen yiqi pill and the gastric saline group，extract the drug-containing serum and normal serum；To set the two groups of serum respectively different concentrations，concentration in different time by CCK8 detection effects on vascular smooth muscle cell proliferation， select best concentration and action time.Flow cytometry instrument and high-throughput screening detect serum medicated effect on vascular smooth muscle cell cycle；Western blot detect the drug-containing serum of cell cycle protein Cyclin D1 and CDK4 expression.Result is 5%， 10% medicated serum inhibits cell proliferation significantly higher than the normal serum concentrations of same within 24 h， 48 h.G1 phase cells 5% medicated serum group was obviously higher than that of 5% in normal group (P<005)， serum and cell proliferation index significantly less than 5% normal serum group (P<005)，At the same time， Cyclin D1 and CDK4 expression significantly less than 5% normal serum group (P<005).Conclusion serum of qishen yiqi pill can inhibit vascular smooth muscle cell proliferation， may be through inhibiting cell cycle protein Cyclin D1 and CDK4 expression， block the cell cycle G1 process is closely related to the role.

Effect of Qishen decoction on dedifferentiation of sinusoidal endothelial cells by autophagy

Objective:To observe the effect of Qishen decoction on dedifferentiation and autophagy of liver sinusoid endothelial cells(LSEC);Methods:LSEC were randomly divided into the control group,model group,Qishen Decoction low,medium,high dose group,and inhibitor group.The model was induced by 100μg/ml oxidized low-density lipoprotein(oxLDL)for 24 hours,and the corresponding drugs or medicated serum were given for intervention.The expression levels of VEGFR2 and ET1 were detected by RT-qPCR and immunofluorescence staining,the ultrastructure of LSEC was detected by transmission electron microscopy,the content of NO was detected by ELISA,the expression levels of autophagy related proteins(LC3BI,LC3BⅡand p62)and endothelial function related proteins(eNOS and p-eNOS)were detected by western blot;Results:The results of transmission electron microscopy showed that Qishen decoction medicated serum could increase the number of fenestra and autophagy in LSEC cells,and inhibit the formation of basement membrane under endothelium.Compared with the model group,Qishen decoction medicated serum could significantly up-regulate the expression level of VEGFR2 mRNA and protein in LSEC,down regulate the expression level of ET1 mRNA and protein,the difference was statistically significant(P<0.05).In addition,Qishen decoction medicated serum could significantly increase the expression of LC3BII,p-eNOS,eNOS protein and the ratio of LC3BII/LC3BI,p-eNOS/eNOS,and reduce the expression of LC3BI and p62 protein in LSEC,which is statistically significant compared with the model group(P<0.05).Conclusion:Qishen decoction can inhibit the dedifferentiation of LSEC by promoting the autophagy level of LSEC,and then play an anti-fibrosis role.

Use of Qishen granule for the treatment of heart failure: A systematic review and meta-analysis of animal studies

Objective:To evaluate the effect of Qishen granule(QSG)on heart failure(HF)and the potential mechanisms involved in animal models.Methods:Studies of QSG in animals with HF were identified by searches of eight databases up to August 1,2019.Two authors independently reviewed each study and the Collaborative Approach to Metaanalysis and Review of Animal Data from Experimental Studies 10-item checklist was used for quality assessment.The primary outcomes were indicators of left ventricular ejection fraction and/or left ventricular fractional shortening.The secondary outcome measures were ventricular structure,hemodynamics,myocardial injury-related indicators,and the mechanisms whereby QSG ameliorates HF.A metaanalysis was performed and all the data were analyzed using RevMan 5.3 software.Results:Thirteen studies containing a total of 240 animals met the criteria for the meta-analysis.The quality score of the studies ranged from three to six points.The meta-analysis showed a significant effect of QSG to improve cardiac function,inhibit ventricular remodeling,improve circulation,and attenuate myocardial injury.The possible mechanisms was identified to be suppression of the renin-angiotensinaldosterone system,which has anti-fibrotic,anti-apoptotic,anti-inflammatory,and anti-oxidative effects in the myocardium,the prevention of calcium overload,and the promotion of myocardial energy metabolism.Conclusion:Our review shows that QSG has a cardioprotective effect in animal models of CHF.However,due to the relatively poor quality of the included studies and the differences between humans and animal models,the results should be interpreted with caution.

A theoretical study of miRNA155-DNA methylation mediated mitokATP regulating mitochondrial autophagy in the improvement of myocardial ischemia-reperfusion injury by Qishen Yiqi Dropping Pills

In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.

Effects of Qishen Yiqi dripping pills-containing serum on KATP channel opening and PI3K/AKT signaling pathway in hypoxic/reoxygenated H9C2 cardiocytes

Objective:To investigate the effects of Qishen Yiqi dropping pills serum on KATP channel opening and PI3K/AKT signaling pathway of hypoxic/reoxygenated H9C2 cardiocytes.Methods:H9C2 cardiocytes cultured in vitro were randomly divided into five groups,A:H9C2 cell group B:H9C2 cells+H2O2 model group C:H9C2 cells+H2O2 model+Qishen Yiqi group D:H9C2 cells+H2O2 model+Qishen Yiqi+wort group E:H9C2 cells+H2O2 model+Qishenyiqi+5-HD group,the drug intervention is according to the corresponding conditions.CCK-8 method was used to detect the cell activity of each group;Western blot was used to detect the expression of AKT and P-Akt proteins in myocardial cells in each group.The current was recorded by the standard patch clamp whole cell recording method,and the current was collected and analyzed by Pclamp6.0 software.Results:CCK-8 test results showed that compared with group A,the activity of myocardial cells in group B was significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,the difference in group C was statistically significant(P<0.01);compared with C,cardiomyocyte activity in D and E group were significantly decreased,and the difference was statistically significant(P<0.05);WB results showed that compared with A,p-Akt protein expression in B,C,D and E groups were significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,p-Akt protein expression in C,D and E group were significantly increased,and the difference was statistically significant(P<0.01),but there was no significant difference in AKT expression among groups(P>0.05);The results of whole cell patch clamp experiment showed that the outward current of B was significantly increased compared with that of A,and the difference between groups was statistically significant(P<0.01);compared with group B,cardiomyocytes in group C further increased the outward current,and the difference between groups was statistically significant(P<0.01);compared with C,the current of D and E group were significantly decreased,with statistical significance between groups(P<0.01).Conclusion:QishenYiqi dropping pills can protect cardiomyocytes by activating p-Akt protein expression and KATP channel opening in H9C2 cardiomyocytes.

Astragalus Salvia Granules to Benefit the Qi (Qishen Yiqi Keli) protects H9C2 cardiomyocytes by suppressing oxidative stress

Objective:To investigate the effects of Qishen Yiqi Keli(QSYQ;Astragalus Salvia Granules to Benefit the Qi)on ROS scavenging and inhibition of NADPH oxidase in an effort to identify new natural antioxidants.Methods:A total of 23 representative components in QSYQ were investigated,their effects on hydrogen peroxide induced ROS were assayed by dichlorofluorescein assay.Lucigenin chemiluminescence was adopted to test the effect on NADPH oxidase activity in H9C2 cardiomyocyte cells,and pyrogallol autoxidation was adopted to test the superoxide scavenging capacity.Results:Nine compounds in QSYQ could significantly inhibited H2O2-induced ROS increase compared with the model group(P<.05),including tanshinone I,salvianolic acid A,danshinone IIA,and cryptotanshinone from salvia root,luteolin from salvia root,harpagoside,harpagide,and angoroside C from scrophularia root.Nine compounds in QSYQ could significantly inhibited the production of
O2in H9C2 cell.Tanshinone I showed a lowest IC50 value 0.07 mM,the other including salvianolic acid A,cryptotanshinone,and salvianolic acid B,luteolin,isochlorogenic acid C,astragaloside IV,and glycyrrhetinic acid.Licochalcone A inhibited the autoxidation of pyrogallol at a low concentration,and tanshinone I showed no significant inhibitory effect from 2 mM to 20 mM.Conclusion:QSYQ had significant effects on ROS scavenging and inhibition of NADPH oxidase.Tanshinone I and salvianolic acid A are potential NADPH oxidase inhibitors.

Network pharmacology research and experimental validation of Qishen decoction in the treatment of non-alcoholic fatty liver disease

Objective:To screen the main active components of Qishen decoction by network pharmacology and predict the target of its treatment for nonalcoholic fatty liver disease(NAFLD),and to verify it by experiments.Methods:The main active components of Qishen decoction and the disease target of NAFLD were screened through the database;the drug disease target network and PPI were constructed by the software of Cytoscape and string database;the enrichment of go and KEGG were analyzed by the database of DAVID;HE staining,red oil O staining,serum biochemical index and Western blot were used to verify the effect mechanism of Qishen Decoction on NAFLD.Results:A total of 207 active compounds and 95 drug-disease-targets of Qishen Decoction were selected in this study.The results of KEGG enrichment analysis showed that the mechanism of Qishen decoction in the treatment of NAFLD involved adipocytokines,insulin signaling pathway,fatty acid biosynthesis,etc.The results showed that Qishen decoction could significantly reduce the liver NAS score and oil red O staining area of NAFLD rats(P<0.05).At meanwhile,Qishen decoction significantly reduced the levels of serum glucose,insulin,HOMA-IR,TC,TG,AST and ALT in NAFLD rats(P<0.05).In addition,Qishen decoction can significantly up regulate the expression of p-INSRβin liver tissue,down regulate the expression of SREBP-1c,Fas and p-ACC(P<0.05).Conclusion:Qishen decoction can improve the insulin resistance of NAFLD rats through insulin signaling pathway,so as to improve NAFLD fat deposition and liver injury.In addition,Qishen decoction can also achieve the therapeutic effect of NAFLD through multiple channels and targets.

Qishen decoction suppresses liver fibrosis by downregulating PI3K/Akt/mTOR signal pathway

Objective:To observe the effect of Qishen decoction on PI3K/Akt/mTOR signal pathway in rats with liver fibrosis;Methods:40 SD rats were randomly divided into four groups: the control group, the model group, Qishen decoction group, and Colchicine group. Except the control group, the remaining three groups were used to establish liver fibrosis model by intraperitoneal injection of carbon tetrachloride. At the end of modeling, Qishen decoction and colchicine group were given corresponding drug gavage treatment, rats in the model group and the control group were treated with equal volume distilled water for 8 weeks. At the end of the treatment, the blood and liver tissues of rats in each group were collected, the liver function indexes and hydroxyproline content were detected by ELISA, the pathological morphology of liver tissue was detected by HE and Masson staining. Immunohistochemical method was used to detect α-SMA protein expression and Western blot was used to detect the expression of α-SMA, Col-I, Col-Ⅲ and key proteins in PI3K/Akt/mTOR signaling pathway.Results: Compared with the model group, Qishen decoction significantly reduced the levels of AST, ALT, and TBIL in serum, and reduced Hyp content, inflammatory score, fibrosis score, and collagen staining area in liver tissue, differences were statistically significant (P<0.05). At meanwhile, Qishen decoction significantly reduce the expression level of α-SMA, CoL-I and Col-Ⅲ in liver tissue(P<0.05). In addition, compared with the model group, Qishen decoction significantly down-regulated the expressions of p-PI3K, p-Akt and p-mTOR in liver tissue, difference were statistically significant (P<0.05).Conclusion: Qishen decoction suppresses liver fibrosis and inhibits the deposition of collagen in liver tissue by down-regulating PI3K/Akt/mTOR signal pathway.

16S rRNA Technology Approach to Explore Mechanism of Qishen Decoction in Improving Nonalcoholic Fatty Liver Fibrosis

Objective: To explore the mechanism of Qishen Decoction in the treatment of nonalcoholicfatty liver fibrosis (NAFLF) by 16S rRNA technology. Methods: NAFLF rat model was established by intraperitoneal injection of carbon tetrachloride combined with high fat diet. During the modeling period, each group was given corresponding drug intervention treatment for 8 weeks. The changes of liver histopathology, serum liver function, lipid and liver fibrosis were analyzed and compared after treatment in each group. The contents of cecum end were collected and the intestinal flora was sequenced by Illumina Miseq platform. Results: Compared with the model group, Qishen Decoction could significantly improve the pathological changes of liver tissue in NALFL rats, and reduce the NAS score, oil red staining area, collagen staining area, ALT, AST, TC, TG, HA, LN, PIIINP and C-IV levels, with significant differences (P<0.05). In addition, compared with the control group, the intestinal flora abundance and diversity of the rats in the model group were significantly reduced (P<0.05), Qishen decoction could significantly increase the abundance and diversity of the intestinal flora of NAFLF rats (P<0.05), and upregulated the abundance of Bacteroidales_S24-7_group_unclassified, Bifidobacterium, Lactobacillu s, Turicibacter, Parabacteroides, Phascolarctobacterium, Lachnospiraceae_NK4A136_group, Coriobacteriaceae_UCG-002, Parasutterella, Odoribacter, Anaerostipes, Ruminococcaceae_unclassified, Allobaculum, Romboutsia, Holdemanella, and Haem ophilus, the difference was statistically significant (P<0.05). Conclusion: Qishen Decoction inhibits liver fibrosis in NAFLF rats by restore the diversity of intestinal flora and increase the abundance of probiotics in intestinal tract.

Effects of adjuvant Qishen Yiqi Drop Pill therapy on renal function changes and prognosis of patients with early diabetic nephropathy

Objective: To study the effects of adjuvant Qishen Yiqi Drop Pill therapy on renal function changes and prognosis of patients with early diabetic nephropathy. Methods: The patients with early diabetic nephropathy treated in our hospital between February 2015 and April 2017 were chosen and divided into two groups by random number table, observation group received Qishen Yiqi Drop Pill combined with conventional therapy and control group accepted conventional therapy. The renal function indexes, cytokine contents and oxygen free radical generation were compared before treatment and 3 months after treatment. Results:Urine UREA levels as well as serum β2 microglobulin (β2-MG), cystatin C (CysC), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), stromal cell-derived factor-1 (SDF-1), interleukin-17 (IL-17), transforming growth factor-β1 (TGF-β1), malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) contents of both groups were significantly lower while superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) contents were significantly higher after treatment, and urine UREA level as well as serum β2-MG, CysC, TNF-α, IL-6, SDF-1, IL-17, TGF-β1, MDA and 8-iso-PGF2α contents of observation group after treatment was significantly lower than those of control group while SOD and T-AOC contents were significantly higher than those of control group. Conclusion: Adjuvant Qishen Yiqi Drop Pill therapy can improve the renal function and reduce the inflammatory response and oxidative stress response in early diabetic nephropathy.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms

Qishen Yiqi Dripping Pills(QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside Ⅳ, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

瑞舒伐他汀联合芪参益气滴丸治疗高血压病合并冠状动脉粥样硬化性心脏病疗效及对动脉斑块的影响

目的探讨瑞舒伐他汀联合芪参益气滴丸治疗高血压病合并冠状动脉粥样硬化性心脏病的疗效及对动脉斑块的影响。方法选择2021年1月—2021年12月120例高血压病合并冠状动脉粥样硬化性心脏病患者作为研究对象,采用随机数字法平均分为观察组与对照组,两组患者均给予抗血小板聚集及瑞舒伐他汀稳定斑块等治疗措施,观察组在此基础上联合芪参益气滴丸治疗。比较两组患者临床疗效,心功能、血脂水平、颈动脉斑块及不良反应发生情况。结果观察组总有效率明显高于对照组(P<0.05)。随之治疗时间延长,两组患者左心射血分数(left ventricular ejection fractions,LVEF)及左心室收缩末内径(left ventricular end-diastolic dimension,LVEDD)均逐渐改善(P<0.05);治疗后14 d、3月观察组LVEF及LVEDD均高于对照组(P<0.05)。两组患者治疗后甘油三酯、血清总胆固醇、低密度脂蛋白胆固醇、同型半胱氨酸、C-反应蛋白均逐渐改善(P<0.05);治疗后3个月、6个月观察组甘油三酯、血清总胆固醇、低密度脂蛋白胆固醇、同型半胱氨酸、C-反应蛋白低于对照组(P<0.05)。两组患者治疗后颈动脉内中膜厚度(carotid intima-media thickness,IMT)及不稳定斑块比例逐渐降低(P<0.05);治疗后3个月、6个月观察组IMT急不稳定斑块比例低于对照组(P<0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论瑞舒伐他汀联合芪参益气滴丸可以更好地促进高血压病伴颈动脉硬化急性心肌梗死患者恢复,更快使血脂异常达标,更有效地抑制颈动脉不稳定斑块形成,且并未增加不良反应。

芪参益气滴丸联合重组人脑利钠肽治疗射血分数保留的心力衰竭的临床研究

目的:探讨芪参益气滴丸联合重组人脑利钠肽治疗射血分数保留的心力衰竭(HFpEF)的临床效果。方法:选择2023年1—10月九江市第一人民医院收治的69例HFpEF患者。采用随机数字法分为A组、B组与C组,各23例。A组采用抗心力衰竭常规治疗;B组在A组基础上给予芪参益气滴丸治疗,C组在B组基础上给予注射用重组人脑利钠肽治疗。比较三组治疗前后左房径(LA)、左室射血分数(LVEF)、左室短轴缩短率(LVFS)、舒张早期二尖瓣峰值流速及舒张末期二尖瓣峰值流速比值(E/A)、血清氨基末端-B型脑钠肽前体(NT-proBNP)及6分钟步行试验(6MWT)结果,记录三组用药期间不良反应发生率及再住院率。结果:治疗前、治疗6周后,三组LA比较,差异均无统计学意义(P>0.05);治疗6周后,三组NT-proBNP均低于治疗前,LVEF、LVFS、E/A、6MWT均高于治疗前,同时,C组NT-proBNP低于A组与B组,LVEF、LVFS、E/A、6MWT均高于A组与B组,差异均有统计学意义(P<0.05)。三组不良反应发生率比较,差异无统计学意义(P>0.05)。三组再住院率比较,差异有统计学意义(P<0.05);C组再住院率低于A组与B组,差异均有统计学意义(P<0.05)。结论:芪参益气滴丸联合重组人脑利钠肽治疗可有效改善HFpEF患者心功能,提高患者步行能力,降低再住院率,安全性高。

芪参六味方抑制内皮-间质转化改善自发性高血压大鼠心肌纤维化的作用机制

目的:研究芪参六味方对自发性高血压大鼠(SHR)心肌纤维化的作用及机制。方法:构建SHR模型,将大鼠分为模型组、中药低浓度组、中药高浓度组、西药组,另以同龄Wistar-Kyoto(WKY)大鼠作为对照组,每组6只,干预12周。干预12周后进行心功能检测,计算心脏收缩功能指标左室射血分数(LVEF)、左室短轴缩短率(LVFS)及心脏舒张功能指标舒张早期跨二尖瓣血流速度(E)与舒张早期二尖瓣环运动幅度(E′)的比值E/E′;干预12周后处死大鼠,取左心室心肌组织,进行苦味酸-天狼猩红染色后观察心肌间质中胶原纤维总面积及Ⅰ型胶原与Ⅲ型胶原面积,计算两种胶原面积比值;蛋白质免疫印迹法(Western Blot)检测心肌组织中心肌纤维化相关指标Ⅰ型胶原、Ⅲ型胶原、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)与内皮-间质转化(EndMT)相关血小板-血管内皮黏附分子(CD31)、血管内皮钙黏蛋白(VE-Cadherin)、α-平滑肌肌动蛋白(α-SMA)、人成纤维细胞特异蛋白1(FSP1)的表达水平;实时荧光定量聚合酶链式反应(RT-PCR)检测EndMT相关指标CD31、VE-Cadherin、α-SMA、FSP1 mRNA的表达水平。结果:干预12周后,与模型组相比,中药高剂量组降低心肌组织MMP-9蛋白表达(P<0.05),中药高剂量组与西药组均可降低心肌间质Ⅰ型胶原、Ⅲ型胶原蛋白表达水平(P<0.01),改善大鼠心脏舒张功能E/E′(P<0.01),降低EndMT相关蛋白α-SMA、FSP1蛋白表达及VE-Cadherin、α-SMA mRNA表达水平(P<0.05或P<0.01)。结论:芪参六味方可以减轻SHR大鼠心肌纤维化程度,改善心脏舒张功能,其作用机制可能与抑制EndMT有关。

杞参益智方改善D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的效应评价研究

目的评价杞参益智方对D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的改善效应。方法小鼠皮下注射D-半乳糖构建亚急性衰老动物模型,分别给予阳性药多奈哌齐(2 mg·kg^(-1)·d^(-1))、杞参益智方低剂量组(1.33 g·kg^(-1)·d^(-1))、高剂量组(2.67 g·kg^(-1)·d^(-1)),连续给药30 d。通过水迷宫和Y迷宫实验评价模型小鼠学习与记忆行为;采用HE染色考察模型小鼠海马损伤情况;采用TUNEL法检测小鼠海马组织凋亡情况;采用ELISA法检测小鼠海马组织中氧化应激因子与炎症因子表达水平;采用Western blot法检测小鼠海马凋亡、氧化应激与炎性应激相关信号通路蛋白表达。结果杞参益智方水提取物显著缩短模型小鼠水迷宫测试中潜伏期和上台前路程(P<0.01),增加穿越平台次数(P<0.01);增加模型小鼠Y迷宫新臂探索时间和次数(P<0.05);抑制模型小鼠海马TUNEL荧光表达(P<0.01);上调氧化应激因子超氧化物歧化酶(SOD)活力(P<0.05)与谷胱甘肽(GSH)含量(P<0.05),下调丙二醛(MDA)含量(P<0.05);下调白细胞介素(IL)-1β、IL-6与肿瘤坏死因子(TNF-α)表达水平(P<0.05,P<0.01);下调凋亡信号通路蛋白Cleaved Caspase-3与Caspase-3表达(P<0.05),上调氧化应激信号通路蛋白Nrf2与HO-1表达(P<0.05),下调炎性应激信号通路蛋白p-NF-κB与NF-κB表达(P<0.05)。结论杞参益智方具有改善D-半乳糖注射亚急性衰老模型小鼠学习与记忆能力的作用,可能与其抑制海马氧化应激与炎性应激作用相关。