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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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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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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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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.