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OBJECTIVE：To e valuate the clinical efficacy and economics of Sodium tanshinone Ⅱ A sulfonate injection combined with conventional medication versus conventional medication in the treatment of angina pectoris of coronary heart disease. METHODS ：Using“Sodium tanshinone Ⅱ A sulfonate”“Danshentong”“angina pectoris ”as Chinese key words and “Sodium tanshinone Ⅱ A sulfonate”“Danshentong”“Angina pectoris ”as English keywords ，the studies were retrieved from Wanfang database ，CNKI，CBM，Cochrane Library ，Medline，Embase，ISI Web of Science and BIOSIS Previews during the inception to Apr. 2019. After literature screening and data extraction ，the included real world cohort studies were evaluated with bias risk tool of Cochrane systematic evaluator manual 5.2.0. Meta-analysis was conducted by using Stata 15.0 software，and publication bias of results was analyzed . The cost-effectiveness analysis was used for pharmacoeconomic evaluate ，and single factor sensitivity analysis and probability sensitivity analysis were carried out for the results of pharmacoeconomic evaluation. RESULTS ： A total of 29 literatures were included ，involving 31 studies and 2 857 patients. Meta-analysis showed that clinical effective rate [RR ＝1.23，95％CI（1.18，1.28），P＜0.001]，ECG effective rate [RR ＝1.29，95％CI（1.20，1.39），P＜0.001] and angina pectoris effective rate [RR ＝1.22，95％CI（1.15，1.29），P＜0.001] of trial group were significantly higher than those of control group. The adverse reactions of the two groups were mild. The above results were likely to be biased in publication. Cost-effectiveness analysis showed that ICER was 72.02 of 2 groups. The sensitivity analysis showed that above results were stable. CONCLUSIONS ： For patients with angina pectoris of coronary heart disease ，therapeutic efficacy of Sodium tanshinone ⅡA sulfonate injection combined with conventional medication is better that of conventional medication ，and the cost is also slightly higher. When the willingness to pay is higher than 7 202 yuan，the combination scheme has the advantage of cost-effectiveness.
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OBJECTIVE：To provide reference for safe and rational use of Sodium tanshinone ⅡA sulfonate（STS）injection in the clinic. METHODS ：The information of the patients who received STS injection from Jan. 2016 to Dec. 2017 were collected from a Grade 3 hospital. According to relevant suggestions in drug package inserts ，drug utilization rationality was evaluated ，and single-factor and multi-factor analysis on the risk and influential factors for ADR/ADE were performed by group design and individual matching to examine their correlation. RESULTS ：Totally 3 283 patients were included in the study. The drug use frequency were less than 1.5，and the drug utilization indexes were less than 1.0，suggesting that the hospital using STS injection was basically reasonable. Irrational use of drugs mainly included that inappropriate indications （46.48％），unreasonable solvent selection（15.84％），and excessive concentration （2.71％）. Patients with renal insufficiency received STS injection ，and then the risk of ADR/ADE increased by correlation analysis （P＜0.05）. CONCLUSIONS ：Irrational use of STS injection in clinics existed ， mainly like off-label drug use ，excessive concentration ，irrational solvent selection. Drug use evaluation and monitoring should be strengthened. For patients with renal insufficiency ，it is necessary to prevent the occurrence of ADR/ADE ．
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In order to investigate the protective effect of tanshinone ⅡA sulfonate on the sciatic nerve activty in rats after cryopreservation as well as the nerve regeneration and functional recovery after allograft and its possible mechanism, Sprague-Dawley (SD) rats were divded into four groups at different doses of tanshinone ⅡA sulfonate (A 0 mg·L⁻¹, B 80 mg·L⁻¹, C 160 mg·L⁻¹, D 480 mg·L⁻¹) cryopreserved at -80 °C for 24 weeks. Fresh control group nerve segments were harvested without cryopreservation. The ultrastructure and the viable cells of the nerve segments after cryopreservation were observed by electron microscopy, calcein-AM/propidium iodide staining, respectively. The expression of Bax and Bcl-2 was detected by Western blot. After cryopreservation, the nerve segments were cultured in vitro for one week, the mRNA and protein level of NGF and GDNF were detected by PCR and Western blot respectively. In addition, the above four cryopreserved groups transplanted to the Wistar rats by allografting (A', B', C', D'). At 16-week postoperation, muscle compound action potential latency and nerve conduction velocity were examined by electrophysiological. The number and the thickness of myelinated nerve fibers were analyzed by toluidine blue staining. The ultrastructure of the sciatic nerve by electron microscopy was observed. According to the results, after the cryopreserved for 24 weeks, compared with groups A and B, the nerve demyelination and vacuolation were weak, and the more viable cells, the decreased Bax and increased Bcl-2, the increased NGF and GDNF in group C and D. At 16-week poseoperation, the results demonstrated that the more larger and thickly regenerated myelinated axons, the shorter latency of muscle compound action potentials and higher nerve conduction velocity in groups C' and D' compared with groups A' and B'. According to these results, tanshinone ⅡA sulfonate exerted a significant protective effect on the viability of the nerves during cryopreservation at -80 °C and promoted nerve regeneration and functional recovery after transplantation especially in middle- and high-dose of tanshinone ⅡA sulfonate.
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OBJECTIVE:To study the protective effect of tanshinoneⅡA(TSⅡA)sulfonate injection against vancomycin(VAN)-induced renal injury model rats and its mechanism. METHODS:72 rats were randomly divided into blank group,model group, positive control group(amifostine,1 mg/kg)and TSⅡA sulfonate injection low-dose,medium-dose and high-dose groups(15,30, 60 μg/kg),with 12 rats in each group. Except for blank group,those groups were given VAN(200 mg/kg)intravenously via tail vein to induce renal injury rat model;after modeling,each drug group was given relevant medicine intraperitoneally once a day, and blank group and model group were given normal saline intragastrically for consecutive 10 days. The levels of 24 h protein, NAG and KIM-1 in urine were determined,and those of Cys C,Scr and BUN in serum and those of SOD,MDA,GSH-Px and NO in renal homogenate were also determined;the pathological change of renal tissue was observed. RESULTS:Compared with blank group,the levels of Cys C,Scr and BUN in serum,those of 24 h protein,NAG and KIM-1 in urine and those of MDA and NO in renal tissue increased significantly in model group,while the levels of SOD and GSH-Px decreased significantly(P<0.01);the pathological slice indicated that model group suffered from renal injury such as kidney tubules albuminoid degeneration,brush border abscission,renal tubular epithelial cell disintegration and abscission. Compared with model group,the levels of Cys C,Scr and BUN in serum,those of 24 h protein,NAG and KIM-1 in urine and those of MDA and NO in renal tissue decreased signifi-cantly in treatment groups,while the levels of SOD and GSH-Px in renal tissue increased significantly(P<0.05 or P<0.01);path-ological changes of renal tissue were relieved significantly. CONCLUSIONS:TSⅡ A sulfonate injection can effectively relieve VAN-induced renal injury in rats,and its mechanism may be associated with inhibiting the oxidative reaction of rats in vivo.
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OBJECTIVE:To observe clinical efficacy and safety of tanshinone ⅡA sulfonate combined with alprostadil in the treatment of acute cerebral infarction. METHODS:56 patients with acute cerebral infarction were randomly divided into treatment group(36 cases)and control group(20 cases). Control group was given tanshinone ⅡA sulfonate 60 mg intravenously,qd,for 10 days. Treatment was additionally given Alprostadil injection 10 μg intravenously,30 min drop lrote,qd,the two group for 10 days,on the basis of control group. Therapeutic efficacy and BI were observed at the end of a treatment course. RESULTS:The ef-fective rate of treatment group and control group were 91.67% and 75.00%,with statistical significance(P<0.05). BI score of 2 groups after treatment were better than before,and the treatment group was better than the control group after treatment,with statis-tical significance (P<0.05). No obvious ADR wad found in both groups. CONCLUSIONS:Tanshinone ⅡA sulfonate combined with alprostadil is effective in the treatment of acute cerebral infarction with good safety.
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OBJECTIVE:To observe the effects of Tanshinone ⅡA sulfonic acid sodium injection on blood supply and blood rheology of patients with central retinal vein occlusion )CRVO). METHODS:92 CRVO patients were selected and randomly divided into control group and trial group with 46 cases in each group. Control group was given routine treatment of laser photocoagulation;trial group was additionally given Tanshinone ⅡA sulfonic acid sodium injection 80 mg added into 0.9% Sodium chloride injection 150 ml,ivgtt,qd. A treatment course of 2 groups lasted for 7 days,and both received 4 courses of treatment. The hemodynamics and hemorheology of central retinal artery (CRA) were recorded in 2 groups before and after treatment. The fluorescence angiogra-phy (FFA) and optical coherence tomography (OCT) of 2 groups were also observed. RESULTS:Before treatment,there was no statistically significant difference in Vmax,Vmin and RI of CRA between 2 groups (P>0.05);after treatment,Vmax,Vmin and RI of CRA in 2 groups were improved significantly,the trial group was better than control group,with statistical significance(P<0.05). After treatment,whole blood high shear viscosity,whole blood low shear viscosity,plasma specific viscosity and fibrinogen of trial group were significantly lower than those of control group,and FFA and OCT of trial group were better than those of control group, with statistical significance(P<0.05). CONCLUSIONS:TanshinoneⅡA sulfonic acid sodium injection can obviously improve hemo-dynamics and hemorheology of CRVO and blood supply and vision of lateral eye.
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Objective To discuss a method combining serum‐pharmacology and electrophysiology technology ,and to research the mechanism of dilating porcine coronary artery of sodium tanshinone Ⅱ‐A sulfonate (DS‐201) .Methods To give mice intragastric administration solution and measure DS‐201 concentration in mice serum ,and apply the serum to single channel patch to research its effect on big conductance calcium‐activated potassium channels(BKca ) in porcine coronary artery smooth muscle cells (PCASMCs) . Results The linear range of concentration containing DS‐201 serum was 0 .73 to 1 .91 μg/mL (r=0 .997 7) ,the recycle rate was 99 .85% -101 .47% ,and the concentration was(7 .32 ± 4 .25)μg/mL ;the result indicates that serum containing DS‐201 has activa‐tion effects on BKCa in PCASMCs ,while there was no statistical significance (P>0 .05) .Conclusion The establishment method of the alcohol extraction of Danshen is useful and reliable .The HPLC method of measuring DS‐201 concentration is precise .Choosing higher quality drugs or raising bioavailability can improve combination of the serum pharmacology and electrophysiological tech‐nique .
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This paper was aimed to study the effectiveness and safety of TanshinoneⅡA Sulfonate Sodium Injection in the treatment of unstable angina pectoris (UAP). Keywords such as coronary atherosclerotic heart disease, coronary heart disease, unstable angina, chest impediment, cardialgia, TanshinoneⅡA Sulfonate Sodium Injection, tanshinone injection, tanshinoneⅡA sulfonate, unstable, angina, randomized controlled trial (RCT), and clinical trials were searched in CNKI, VIP, Wanfang and Pubmed from the construction of database until October 31st, 2014. The inclusion criteria were RCT with clinical data integrity, similar literature research methods, and good balance between groups. The Jadad score method was used to carry out quality assessment. Meta-analysis was conducted by RevMan5.2 software. Count data was processed by odds ratio (OR). Measurement data was processed with the weighted mean differences (WMD). The 95% confidence interval (CI) was also calculated. The heterogeneity test result of included literatures was P > 0.05. The fixed effects model was used in the meta-analysis. On the other hand, random effect model was used. For the analysis results of more than 10 papers, the funnel plot was used in the analysis of publication bias. The results showed that a total of 34 studies were included. The results of meta-analysis suggested that the total efficiency of conventional treatment plus TanshinoneⅡA Sulfonate Sodium Injection for UAP was [OR = 3.83, 95%CI (3.11, 4.71),P < 0.000 01]. The electrocardiogram improvement rate was [OR = 3.34, 95%CI (2.61,4.28),P < 0.000 01]; plasma viscosity improvement was [WMD = -0.20, 95%CI (-0.38, -0.03),P = 0.03]; high shear viscosity of whole blood improvement was [WMD = -0.67, 95%CI (-0.85, -0.50),P < 0.000 01]; C-reactive protein improvement was [WMD = -2.66, 95%CI (-3.31, -2.00),P < 0.000 01]. It was concluded that the conventional treatment plus TanshinoneⅡA Sulfonate Sodium Injection for UAP had certain clinical effect with no obvious adverse reaction. However, due to the poor quality of the existing research literatures, the results should be further verified by large amount of high quality RCTs.
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Objective To investigate the protective effect of sodium tanshinone ⅡA sulfonate(STS) on adriamycin-induced H9c2 cell apoptosis. Methods H9c2 cells were divided into four groups: the control group, the ADR group, the STS group, and the AS(ADR+STS) group. MTT assay were used to detect cell proliferation and cell death. The cell cycle of H9c2 cells were determined by flow cytometry assay. Protein expression of Bcl-2, Bax and Caspase-3 was detected by Western blot assay. Results Compared with the control group, cell proliferation was significantly reduced , and the number of the cells was significantly increased in the G0/G1 phase in the ADR group(P < 0.01, P < 0.05). At the same time, the expression of Caspase-3 was dramatically enhanced and the ratio of Bcl-2/Bax was significantly reduced (P < 0.05, P < 0.01) in the ADR group. However, pretreatment of STS increased H9c2 cell proliferation, decreased the number of the arresting cells, inhibited the expression of Caspase-3, and improved the ratio of Bcl-2/Bax (P < 0.05, respectively). Conclusions STS can attenuate ADR-induced myocardial cell apoptosis.
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To explore the protective effect of sodium tanshinone Ⅱ A sulfonate (STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture (CLP).Rats were randomly divided into 3 groups:sham operated group (S),sepsis group (CLP) and STS treatment group (STS).STS (1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay (ELISA).The expression of intercellular adhesion molecule-1 (ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB (NF-κB) and tissue factor (TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP (P＜0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α (P＜0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.
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Summary: The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ (Ang Ⅱ)-induced hypertrophy and effects of sodium tanshinone Ⅱ A sulfonate (STS) in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction (RT-PCR). It was found after cardiomyocytes were treated with Ang Ⅱ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly (P<0.01). After treatment with Ang Ⅱ for 24 h, the rate of protein synthesis in Ang Ⅱ group was significantly increased as compared with control group (P<0.01). After treatment with Ang Ⅱ for 7 days, the size of cardiomyocytes in Ang Ⅱ group was increased obviously as compared with control group (P<0.05). After pretreatment with STS or Valsartan before Ang Ⅱ treatment, both of them could inhibit the above effects of Ang Ⅱ (P<0.05 or P<0.01). It was suggested that STS could ameliorate Ang Ⅱ-induced cardiomyocyte hypertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.
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[Objective]To observe the effect of tanshinone Ⅱ A sulfonate injection on rheology of coronary heart disease angina, and discuss the functional mechanism of the treatment. [Method] Administer tanshinone Ⅱ A sulfonate to 25 cases for treatment group, the control group 23 take low molecular weight dextran and heparin by vein dripping, make comparison of both, observe their rheology indexes.[Result] In treatment group, the blood mucosity was reduced a lot, the thrombosis in vitro was shortened markedly, whose wet weight and dry weight were decreased, and the coagulation was obviously relieved. [Conclusion] Vein dripping tanshinone Ⅱ A sulfonate injection can improve markedly the blood rheological indexes of the patients of coronary heart disease angina.
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Aim To observe effects of Sodium tanshinoneⅡA sulfonate(STS) on angiotensionⅡ(AngⅡ)-induced cardiomyocyte hypertrophy and the expression of phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2). Methods In the primary culture of neonatal rat cardiomyocytes, as indexes of cardiomyocyte hypertrophy, the total protein was determined by coomassie brilliant blue and protein synthesis rate was measured by [3H]-Leucine incorporation. The expression of p-ERK1/2 was assessed using Western blot and fluorescence microscope. Results ① The total protein and protein synthesis rate stimulated by Ang Ⅱ(1 ?mol?L-1)in the cardiomyocytes increased significantly in contrast to that of control; STS could effectively decrease the increased total protein level induced by Ang Ⅱand markedly inhibit synthesis of protein. ② AngⅡ(1 ?mol?L-1) had the effect of promoting activation of ERK1/2 and then appeared in nucleus rapidly. The translocation process of ERK1/2 induced by AngⅡ was blocked distinctly by STS. ③ Cardiomyocyte pretreated with Ang Ⅱ(1 ?mol?L-1)for 5 min, the p-ERK1/2 protein expression began to increase ,the peak effect was at 10 min. While pretreatment with STS(2, 10, 50 ?mol?L-1) ,Ang Ⅱ-induced increase in p-ERK1/2 were inhibited evidently. ④ In pretreatment of cardiomyocyte with STS in different doses for 30 min, STS was found to be able to inhibit the expression of p-ERK1/2 stimulated by AngⅡ in a dose-dependent manner. Conclusions The results suggested that activation of ERK1/2 might play an important role in cardiomyocytes hypertrophy induced by Ang Ⅱ,and the anti-hypertrophic effect of STS on cardiomyocyte hypertrophy induced by AngⅡ might be associated to its inhibitory effect on ERK signaling pathway.