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The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.
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ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.
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eration-toxicity test kit was used to detect the cell viability of astrocytes, and flow cytometry to detect mitochondrial membrane potential, KOS release and intracellular calcium concentration.KT-PCK was employed to detect the niHNA expression of BDNF, NGF, KtFIcx in astrocytes.Western blot was used to detect the phosphorylation of PI3K, ART and STA'13 protein in astrocytes.Results OGD/K significantly decreased cell viability.HOS release and intracellular calcium ion concentration of astrocytes, mitochondrial membrane potential and p-STAT3 , p-PI3K, p-AKT ex¬pression decreased in OGD/R group.Sal 15, Rgl and HI significantly increased the viability of damaged cells, and regulated KOS release, calcium ion concen¬tration and mitochondrial membrane potential to varying degrees.Sal B and Rgl increased the expression of p- STA'13 and p-AKT.Hie expression of BDNF and NGF niRNA in OGD/R group significantly decreased, and Sal B, Hgl and HI could significantly increase the ex¬pression of BDNF niHNA in damaged cells.Hgl could increase NGF niRNA expression.Sal B increased the expression of IGFla niRNA.Conclusions Sal B, Kgl, and HI reduce the oxidative stress response of astrocytes after OGD/R injury by regulating the PI3K/ ART and STA'13 signaling pathway, reduce intracellu¬lar calcium overload, and play a protective role in as-trocytes, increase the release of astrocyte neurotrophic factor, which may further play a protective role in neu¬rons.
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OBJECTIVE：To study the improve ment effect of salvianolate on renal interstitial fibrosis （RIF）model rats and its possible mechanism. METHODS ：Totally 50 male SD rats were randomly divided into normal group ，model group ，losartan group （positive control group ，9 mg/kg）and salvianolate low-dose and high-dose groups （18，36 mg/kg）according to body weight ，with 10 rats in each group. Except for normal group ，other groups were given adenine 250 mg/kg intragastrically to establish RIF model. After modeling ，administration groups were given relevant medicine intragastrically ，and normal group and model group were given constant volume of normal saline intragastrically ，the volume was 10 mL/kg，once a day ，for consecutive 30 days. After last medication，the serum levels of creatinine （Scr），urea nitrogen （BUN）and 24 h proteinuria （24 h UPro ）were detected by ELISA. HE staining and Masson staining were used to observe the histopathological characteristics and fibrosis of the kidney. The degree of renal tubular injury and glomerulosclerosis were scored ，and the percentage of positive staining area of renal tissue was calculated ； immunohistochemistry and Western blot assay were used to determine the protein expression of Wnt 5a，Wnt5b，and β-catenin. RESULTS：Compared with normal group ，Scr，BUN and 24 h UPro levels ，renal tubular injury score ， glomerulosclerosis score ， the percentage of positive staining area in renal tissue ，the protein expression of Wnt 5a and β-catenin were increased significantly in model group （P＜0.05），while the expression of Wnt 5b protein was decreased significantly （P＜0.05）. Pathological changes such as mesangial hyperplasia ，fibrous tissue increase and inflammatory cell infiltration were observed under microscope. Compared with model group ，above indexes of rats were improved significantly in losartan group ，salvianolate low-dose and high-dose groups （P＜ 0.05），and the effect of salvianolate had dose-dependent trend. CONCLUSIONS ：Salvianolate has the improvement effect on RIF model rats induced by adenine ，and its mechanism may be related to inhibition of Wnt/ β-catenin signal pathway.
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OBJECTIVE@#To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients.@*METHODS@#A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI.@*RESULTS@#Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups.@*CONCLUSIONS@#Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992].
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OBJECTIVE@#To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients.@*METHODS@#A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI.@*RESULTS@#Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups.@*CONCLUSIONS@#Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992].
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Objective:To investigate the effect of salvianolate lyophilized injection and Xueshuantong injection (lyophilized) on the permeability of blood-brain barrier (BBB) via inhibition of metallomatrix protease（MMPs） in cerebral ischemia/reperfusion injury rats. Method:The focal cerebral ischemia/reperfusion model in rats was built by middle cerebral artery occlusion/reperfusion (MCAO/R) technique. Male Wistar rats were randomly divided into sham operation group, ischemia/reperfusion (I/R) group, edaravone (Eda, 6 mg·kg-1) group, salvianolate lyophilized injection (SLI, 21 mg·kg-1) group, Xueshuantong (XST, 100 mg·kg-1) group and SLI combined with XST (SLI+XST, 21 mg·kg-1+100 mg·kg-1) group. Drugs were injected via tail vein for 2 d, while sham group and I/R group were injected with the same amount of normal saline. Neurological deficit score, hematoxylin-eosin (HE) staining and Nissl staining were assessed 2 d after MCAO/R. The permeability of BBB was observed by the leakage of IgG/CD31. The expressions of Claudin-5，Occludin，collagen-Ⅳ（Col- Ⅳ），Laminin，Fibronectin were observed by immunofluorescence staining，and MMP-2 and MMP-9 were observed by Western blot. Result:Compared with the I/R group, SLI group, XST group and SLI+XST group showed improvements in neurological deficit score, HE staining and Nissl staining. The leakage of IgG was alleviated; The positive expressions of Claudin-5，Occludin，Col-Ⅳ，Laminin，Fibronectin in ischemic penumbra were significantly up-regulated, while the expressions of MMP-2 and MMP-9 were down-regulated. The effect in improving SLI combined with XST was much better than a single factor. Conclusion:Salvianolate lyophilized injection and Xueshuantong injection (lyophilized) can alleviate cerebral ischemia/reperfusion injury and exert the synergistic effect when they are used in combination. The mechanisms might be associated with the improvement in the permeability of blood-brain barrier by inhibiting MMPs in cerebral ischemia/reperfusion injury rats.
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Objective::To study the degradation of salvianolate lyophilized injection (SLI) and establish a stability-indicating analysis method. Method::UPLC-Q-TOF-MS/MS was used to conduct a qualitative study on the main components of SLI, and a stability-indicating analysis method was established for simultaneous determination of the original components of SLI and its degradation products. The stability of SLI were systematically assessed under physicochemical conditions of high temperature, oxidation, metal ions. Result::Totally 13 main active ingredients in SLI were identified, and a semi-quantitative analysis was performed. Under the conditions of high temperature, oxidation, light, trivalent ion and divalent ion, 6, 4, 3, 4 and 1 new degradation products were added respectively. The established stability-indicating analysis method can simultaneously determine the degradation products of the main components and their active components in SLI, with a good separation effect. Conclusion::According to the degradation mechanism of the main ingredients in SLI, macromolecular polyphenol acid compounds are degraded into small molecular compounds, such as tanshinol and protocatechu aldehyde by a series of reactions, like benzofuran open-loop, hydrolysis of ester bond and removal of DSS. The stability-indicating analysis method can be used for the stability quality control of traditional Chinese medicine Salvianolate Lyophilized Injection (SLI).
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Objective To investigate the protective effect of salvianolate against bile duct injury after donation after cardiac death (DCD) liver transplantation and its clinical application prospect. Methods Sixty recipients of DCD liver transplantation were randomly divided into two groups with 30 cases in each group. Salvianolate (250mg/d) was given daily for 14 days after operation in treatment group, and the same amount of normal saline was given in control group. The therapeutic regimen of anti-rejection and anti-infection is the same between the two groups. The incidence of early graft dysfunction (EAD), and the serous levels of total bilirubin (TB), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), total bile acid (TBA) 1 month, 6 months and 12 months after liver transplantation were compared between the two groups. Also, the platelets (PLT), prothrombin time (PT), activated partial prothrombin time (APTT) and fibrinogen (FIB) were compared between the two groups at 2 weeks after operation. Results There was no significant difference in baseline parameters between the two groups (P>0.05). Compared with the control group, the incidence of EAD was decreased in treatment group, but there was no significant difference [10.0%(3/30) vs. 23.3%(7/30), P=0.166]. The serous levels of TB, ALP, GGT and TBA in treatment group were lower than those in control group 1 month, 6 months and 12 months after operation: [TB: 1 month, (28.5±17.0)μmol/L vs. (39.8±20.1)μmol/L, P=0.025; 6 months, (24.5±10.6)μmol/L vs. (33.3±16.4) μmol/L, P=0.018; 12 months, (19.8±9.5)μmol/L vs. (26.4±14.1)μmol/L, P=0.037, ALP: 1 month, (147.3±76.9)U/L vs. (187.6±70.9)U/L, P=0.039; 6 months, (163.0±61.4)U/L vs. (198.1±51.6)U/L, P=0.020; 12 months, (167.9±59.9)U/L vs. (200.2±56.2)U/L, P=0.036, GGT: 1 month, (83.9±49.5)U/L vs. (113.6±61.1)U/L, P=0.043; 6 months, (130.9±48.7)U/L vs. (169.7±77.0)U/L, P=0.023; 12 months, (154.7±45.1)U/L vs. (182.5±59.8)U/L, P=0.047, TBA: 1 month, (6.6±2.1)μmol/L vs. (8.0±2.4)μmol/L, P=0.016; 6 months, (9.5±2.2)μmol/L vs. (12.1±3.4)μmol/L, P=0.001; 12 months, (12.5±2.7)μmol/L vs. (5.6±3.8)μmol/L, P=0.001]. However, there was no significant difference in PLT, PT, APTT and FIB between two groups [PLT: (148.6±88.6)×109/L vs. (152.8±74.4)×109/L, P=0.843; PT: (12.9±1.1)s vs. (13.0±1.1)s, P=0.617; APTT: (34.6±3.7)s vs. (34.9±3.4)s, P=0.716; FIB: (3.4±0.6)g/L vs. (3.2±0.6)g/L, P=0.270, repectively]. Conclusions Salvianolate has a protective effect against bile duct injury after DCD liver transplantation, and does not increase the risk of postoperative bleeding.
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OBJECTIVE@#To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP).@*METHODS@#A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events.@*RESULTS@#Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated.@*CONCLUSIONS@#Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].
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To systemically evaluate the efficacy and safety of salvianolate intravenous drip in combination with hydration against contrast-induced nephropathy( CIN),and guide clinical medication. Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,VIP,Wan Fang database,CNKI) were retrieved to collect the randomized controlled trials( RCTs) about the efficacy of salvianolate intravenous drip in combination with hydration( trial group) vs routine hydration( control group) in the prevention of contrastinduced nephropathy. The methodological quality of the RCTs was evaluated by using the Cochrane 5. 1. 0 Bias Risks Assessment Tool.The data were extracted and Meta-analysis was conducted by Reviewer Manager 5. 3. Egger's test and non-parametric clipping method were used to evaluate publication bias. A total of 9 RCTs with 2 186 participants were included. RESULTS:: of Meta-analysis showed that the incidence of contrast-induced nephropathy of trial group was significantly higher than that of control group( RR = 0. 46,95% CI[0. 35,0. 59],P<0. 001). Subgroup analysis showed that the incidences of CIN in patients with acute coronary syndrome( ACS) undergoing PCI,in patients with the average age≥65 years,in patients who received mean contrast volume ≥200 m L,in patients with serum creatinine( Scr) ≥ 80 μmol,or in patients who received intraoperative administration of salvianolate or PCI were higher than those in control group,with statistically significant differences( P<0. 05). The experimental group was superior to the control group in improving the indexes of renal function after operation,and the difference was statistically significant( P<0. 05). No study reported the incidence of adverse reactions( ADRs). The funnel plots of the incidence of CIN showed potential publication bias. The results of Egger's linear regression showed that there was certain publication bias. Sensitivity analysis,funnel plot,and " trim and fill" showed that the results of this study were stable and reliable. Salvianolate combined with routine hydration showed definite clinical efficacy in the prevention of contrast-induced nephropathy. However,exact conclusion should be further verified by additional high-quality,multi-centre,and large-scale RCT studies.
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Humans , Contrast Media , Kidney Diseases , Percutaneous Coronary Intervention , Plant Extracts , Therapeutic Uses , Randomized Controlled Trials as TopicABSTRACT
Objective To observe the effects of salvianolate on blood biochemical indexes, pathological changes of renal tissue and expression of CD2AP and Desmin protein in membranous nephropathy rats induced by cationic bovine serum albumin. And to explore the renal protective effect of salvianolate on membranous nephropathy rats and its possible mechanism. Methods Healthy male SD rats were randomly divided into normal group and modle group. Rat models of membranous nephropathy were reproduced by injection of cationized bovine serum albumin through tail vein. Model successful rats were randomly divided into model group, benazepril group, and salvianolate groups (16.7, 33.3, and 66.7 mg/kg). Each group was given the dose of the corresponding drugs. After treatment, the level of 24 h urine total protein (UTP), serum total cholesterol (TC), triglyceride (TG), total protein (TP), albumin (ALB), urea nitrogen (BUN), and serum creatinine (Scr) were detected. Immunofluorescence, light microscope, and electron microscope were used to observe the pathological changes of rat kidney. Immunohistochemistry and real-time PCR were used to detect the expression of CD2AP and Desmin. Results Compared with the control group, levels of UTP, TC, and TG increased significantly (P < 0.01), levels of serum TP and ALB decreased significantly (P < 0.01) in the model group. Compared with the model group, the UTP, TC, and TG of each treatment group were significantly decreased (P < 0.05, 0.01), while the TP and ALB were significantly increased (P < 0.01). There was no significant difference in the UTP, TC, TG, TP, and ALB among each dosage of salvianolate and benazepril group. And there was no significant difference among each dose group of salvianolate. There was no significant difference among each groups in the level of BUN and Scr. Compared with the normal group, the expression of CD2AP in model group was significantly decreased and Desmin was significantly increased (P < 0.01). Compared with the model group, the expression of CD2AP increased and Desmin decreased in each treatment group (P < 0.01), but there was no difference among the treatment groups. Conclusion Salvianolate has kidney protective effect on membranous nephropathy rats. The mechanism may be related to up-regulating the expression of CD2AP, down-regulating the expression of Desmin, inhibiting podocyte injury and protecting the integrity of the glomerular filtration barrier.
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Objective:To investigate the clinical efficacy of salvianolate in the treatment of ischemic stroke(IS) and its effect on the serum levels of uric acid, hypoxia Inducible Factor-1α (HIF-1α), neuroglobin (NGB), hypersensitive C-reaction protein (hs-CRP),regulatory T cell(Treg) and helper T lymphocyte 17 (Th17). Methods:Totally 196 IS patients in our hospital were analyzed and divided into the control group(n=96) and the observation group(n=96). The patients in the control group were treated with the traditional therapy,and the patients in the observation group were treated with salvianolate additionally. The clinical effect and disabili-ty were observed;and the serum levels of uric acid,HIF-1α,NGB,hs-CRP,Treg and Th17 were compared between the groups. Re-sults:Before the treatment,there were no differences in uric acid,HIF-1α,NGB,hs-CRP,Treg and Th17 between the groups(P>0.05). After the 14-day treatment,the effective rate was 69.79% in the observation group,which was higher than that in the control group (P<0.05). NIHSS scores and mRS scores of the two groups were lower than baseline values (55.21%,P<0.05). After 3-month follow-up,NIHSS scores,mRS scores and the disability rate(12.5%) in the observation group were obviously lower than those in the control group(P<0.05). After the 14-day treatment,the serum levels of uric acid,HIF-1α,NGB,and hs-CRP in the obser-vation group were lower than those in the control groups (P<0.05). Besides, the patients in the observation group were with more Treg and fewer Th17 than the control group and baseline value (P<0.05). Conclusion:The application of salvianolate in the treat-ment of ischemic stroke can effectively improve the disability and neurological function defects,which should be recommended for the clinical use as an effective drug.
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Objective: Inflammatory reactions induced by microglia in the brain play an important part in the pathogenesis of focal cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death. Salvianolate Lyophilized Injection (SLI) and Xueshuantong Injection (Lyophilized) (XST), which have been widely used in the treatment of acutely cerebral infarction clinically in China, exhibit various biological activities. In this study, the neuroprotective properties of SLI combined with XST in a rat model of middle cerebral artery occlusion- reperfusion (MCAO/R) were investigated. Methods: In this study, male Wistar rats were subjected to 1.5 h of middle cerebral artery occlusion followed by reperfusion for 24 h. The rats were randomly divided into the following six groups: normal group (NOR), model group (MOD), SLI group (21 mg/kg, SLI), XST group (100 mg/kg, XST), SLI combined with XST (XST 100 mg/kg + SLI 21 mg/kg, 1X1S), and Edaravone (as a positive control drug, 6 mL/kg, EDI), once a day for 3 d. The neuronal injury, the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), and the changes of pro-inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and anti-inflammatory mediator interleukin-10 (IL-10) were observed. Results: 1X1S treatment significantly increased the number of neuron, compared with the MOD group, SLI group and XST group. Gliosis (GFAP and IBA-1) and expression of pro-inflammatory mediators IL-6 and TNF-α were significantly reduced. Meanwhile, 1X1S significantly increased the expression of anti-inflammatory mediator IL-10 in the brains of MCAO/R rats, compared with the MOD group, SLI and XST groups. SLI and XST also remarkably down-regulated the expression of IL-6 and TNF-α compared with the MOD group. Conclusions: This study shows that SLI combined with XST (1X1S) can protect cerebral ischemia-reperfusion injury due to its anti-inflammatory property, and may provide a potential promising new therapeutic strategy for acute ischemic stroke.
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OBJECTIVE: To explore the curative effect of combination therapy with salvianolate injection (SAFI) and aspirin on anti-platelet aggregation and blood coagulation function, provide the experimental evidence for clinical consequence use of combination therapy with traditional Chinese medicine and western medicine. METHODS: The bleeding time was measured by cutting tail evaluating of combination of drugs; platelet maximum aggregation rate induced by ADP, AA, collagen and thrombin in rats was determined by absorbance method using a microplate reader; blood coagulation of the four indicators were measured by the semiautomatic blood agglutination instrument. RESULTS: SAFI had nearly no effects on aspirin group's bleeding time. The effect on blood platelets aggregation compared with control group, SAFI group and aspirin group could significantly reduce platelet aggregation induced by ADP, AA, collagen and thrombin in normal rats(P<0.01). Combinative group could significantly increase aspirin group's anti-platelet aggregation induced by ADP, AA, collagen and thrombin in normal rats(P<0.01, P<0.05). Coagulation function SAFI can reduced aspirin group's TT after the combination therapy. CONCLUSION: SAFI can increase anticoagulation effect of aspirin, and have no effect on aspirin's bleeding risk.
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Objective To compare the cost-effectiveness of Danshenchuanxiongqin injection versus salvianolate injection for angina pectoris.Methods Databases including CBM,CNKI,VIP,Cochrane library,Pubmed,Embase and Wanfang were electronically searched for the randomized controlled trials(RCTs)on the comparison between Danshen Chuanxiongqin injection and Dsnshenduofensuanyan injection.Literatures were screened and data were extracted in accordance with the inclusion and exclusion criteria.Clinical efficacy of the two drugs were obtained through indirect Meta-analysis.Economic evaluation was carried out using the cost-effectiveness analysis,direct medical cost data included the cost of conventional treatment,drug,ex-amination and hospital expenses.Results Through indirect Meta-analysis,the improvement efficiency of angina were 89.51%and 92.52% for Danshenchuanxiongqin injection and salvianolate injection.The success rates of ECG were 81.40% and 84·05% for two drugs. The costs of Danshenchuanxiognqin injection and salvianolate injection were 4 099.71 and 5 410.16 CNY.The Cost-effectiveness ratio of angina improve of two drugs were 45.80 and 58.48,while the ECG improve were 50.36 and 64.37.And the sensitivity analysis results were stable.Conclusion Compared to salvianolate injection,salvi-anolate injection was probably cost-effective for angina pectoris.
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<p><b>OBJECTIVE</b>To evaluate the preventive effect of salvianolate (Sal B) on glucose metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats.</p><p><b>METHODS</b>Fifty-five Wistar rats were randomly divided into a control group (n=10) and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups (n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B (50 mg/kg), metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline (HYP) and liver function were detected at the end of the treatment. Area under the curve (AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining (HE), Sirius Red staining and Masson's trichrome staining, respectively. Hepatic expression of α-smooth muscle actin (α-SMA) and collagen (Col I) were evaluated by immunohistochemical staining.</p><p><b>RESULTS</b>Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently than Sal B (P<0.05).</p><p><b>CONCLUSIONS</b>Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.</p>
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<p><b>OBJECTIVE</b>To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.</p><p><b>METHODS</b>Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.</p><p><b>RESULTS</b>There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).</p><p><b>CONCLUSION</b>Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.</p>
Subject(s)
Animals , Male , Blotting, Western , Cardiotonic Agents , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Heart Ventricles , Pathology , MAP Kinase Signaling System , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Myocardial Reperfusion Injury , Drug Therapy , Pathology , Organ Size , Phosphorylation , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Protein Kinase Inhibitors , Pharmacology , Staining and LabelingABSTRACT
To investigate the effect of Salvianolate Lyophilized Injection (SLI) combined with Xueshuantong Injection (XST) on expression of astrocytes and microglia in cerebral ischemia-reperfusion injury rats. Methods The Wistar rats (250-300 g, male) were randomly divided into six groups: control group, model group, Edaravone group (6 mg/kg, EDI), SLI group (21 mg/kg), XST group (100 mg/kg), and SLI+XST group (1X1S, 21 mg/kg and 100 mg/kg). Rat model of cerebral ischemia-reperfusion injury was created by the middle cerebral artery occlusion (MCAO) by longa method. Drugs were administered tail intravenous injection once a day for 3 d starting from 24 h after reperfusion. The body weight, neurological deficit scores and survival percentage were observed in 3 d after the cerebral ischemia. The expression of GFAP and IBA-1 was determined at 3 d by immunofluorescence. The complicated compound-target-stroke network of SLI and XST was constructed and analyzed by IPA. Results Compared with the model group, 1X1S could significantly improve the neurological dysfunction, increase the body weight, and inhibit the expression of GFAP and IBA-1 in ischemic penumbra (P < 0.01), IPA reveals the molecular mechanism of SLI and XST in the active ingredient and related targets. Conclusion 1X1S has significant protection on cerebral ischemia reperfusion injury in rats, which may be related to the inhibition of the expression of GFAP and IBA-1 and high mobility group box-1 signaling and Interleukine-8 signaling.
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Objective@#To investigate the effect and related mechanism of salvianolate on myocardial ischemia-reperfusion (I/R) injury in rats.@*Methods@#Thirty-six adult Sprague-Dawley rats were divided into three groups (n=12 each) using random number table method: control group (coronary artery was not ligated) , I/R group (myocardial I/R model was established by ligation and opening of left anterior descending coronary artery) , and salvianolate+I/R group (5 mg/kg of salvianolate was injected through the tail vein at the time of reperfusion) .Triphenyltetrazolium chloride (TTC) stain was utilized to measure the myocardial infarct size. The ELISA method was used to detect myocardial necrotic markers, including cardiac troponin T (TnT) , creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) . Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to analyses the levels of apoptosis. The levels of cleaved Caspase-3 protein were analyzed with Western blot.Cold luminescence method was used to detect the ATP level of myocardial tissue. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in myocardial tissue were detected by immunofluorescence.@*Results@#(1) The infarct size in control group, I/R group and salvianolate+I/R group were 0, (23.90±5.66) %, and (12.06±5.97) %, respectively (P<0.01 or 0.05) . (2) The TnT level was (0.04±0.03) , (16.96±2.80) , and (6.95±2.31) ng/ml, the CK-MB level was (43.6±23.5) , (1 135.8±180.6) ,and (390.3±121.5) U/L, the LDH level was (119.0±58.6) , (1 838.6±543.8) , and (631.6±228.3) U/L in control group, I/R group and salvianolate+I/R group, all significantly lower in salvianolate+I/R group than in I/R group (all P<0.01) . (3) The rate of TUNEL positive myocardial cells were (1.07±1.16) %, (21.36±4.11) %,and (13.30±3.67) % in control group, I/R group,and salvianolate+I/R group (all P<0.01) . (4) The cleaved Caspase-3 expression was 0.11±0.05, 0.84±0.20,and 0.43±0.09 in control group, I/R group, and salvianolate+I/R group (all P<0.01) . (5) The ATP level of myocardial tissue was (100.0±0.0) %, (34.2±9.2) %,and (62.1±18.0) % respectively in control group, I/R group, and salvianolate+I/R group (all P<0.01) . (6) There was almost no 8-OHdG expression in the myocardial tissue of control group. The expression of 8-OHdG in the myocardial tissue of I/R group was greater than that of the control group. The expression of 8-OHdG in the myocardial tissue of salvianolate+I/R group was less than that of the I/R group.@*Conclusion@#Salvianolate may alleviate myocardial I/R injury of rat through reducing the mitochondrial DNA oxidative damage, protecting mitochondrial function and inhibiting the apoptosis of myocardial cells.