Sodium Tanshinone ⅡA Sulfonate Ameliorates Microcirculatory Disturbance of Small Intestine by Attenuating the Production of Reactive Oxygen Species in Rats with Sepsis

Objective: To examine whether sodium tanshinone ⅡA sulfonate(STS), the main effective component of Salvia miltiorrhiza is effective in relieving the microcirculatory disturbance of small intestine by suppressing the production of reactive oxygen species(ROS) in rats with sepsis. Methods: A rat model of sepsis was induced by cecal ligation and puncture(CLP). Rats(n=40) were randomly divided into 4 groups: sham-operated group(sham, n=10), sepsis group(CLP, n=10), STS treatment group(STS, n=10) and ROS scavenger dimethylthiourea(DMTU, n=10) group. Animals in the STS group were injected with STS(1 mg/kg) for 10 min through the right external jugular vein after the CLP operation, and animals in the CLP group were given the same volume of normal saline after the CLP operation. Animals in the DMTU group were intraperitoneally injected with 5 m L/kg of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues and changes of mesenteric microcirculation were observed. The levels of ROS in intestinal tissues from each group were qualitatively evaluated using a fluorescent microscope. The expressions of apoptosis signal-regulating kinase(ASK1), phosphorylated ASK1(phospho-ASK1), p38 mitogen-activated protein kinases(p38 MAPK), phosphorylated p38 MAPK(phospho-p38 MAPK) and tissue factor(TF) were determined by Western blotting. Results: It was shown that there were obvious microcirculatory disturbance(P0.05) and tissue injuries in intestinal tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho-p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1, phospho-p38 MAPK and TF production, and ameliorated the microcirculatory disturbance and tissues injury(P0.01). Conclusion: STS can ameliorate the microcirculatory disturbance of the small intestine by attenuating the production of ROS in rats with sepsis.     

Protective Effect of Tanshinone Ⅱ A on Lipopolysaccharide-induced Lung Injury in Rats

Objective:To explore the protective effect of tanshinoneⅡA on lipopolysaccharide(LPS)-induced lung injury in rats,and possible mechanism.Methods:LPS(O111:B4) was used to produce a rat model of acute lung injury.Sprague-Dawley rats were randomly divided into 3 groups(8 in each group):the control group,the model group(ALI group),and the tanshinoneⅡA treatment group.Expression of adhesion molecule CD18 on the surface of polymorphonuclear neutrophil(PMN-CD18) in venous white blood cells(WBC),and changes in coagulation-anticoagulant indexes were measured 6 h after injection of LPS or normal saline.Changes in malondialdehyde(MDA) content,wet and dry weight(W/D) ratio and morphometry of pulmonary tissue as well as PMN sequestration in the lung were also measured.Results:(1) When compared with the control group,expression of PMN-CD18 and MDA content were enhanced in the ALI group with a hypercoagulable state(all P<0.01) and an increased W/D ratio(P<0.05).Histopathological morphometry in the lung tissue showed higher PMN sequestration,wider alveolar septa;and lower alveolar volume density(VV) and alveolar surface density(SV),showing signif icant difference(P<0.01).(2) When compared with the ALI group,the expression of PMN-CD18,MDA content,and W/D ratio were all lower in TanshinoneⅡA treatment group(P<0.05) with ameliorated coagulation abnormality(P<0.01).Histopathological morphometry in the lung tissue showed a decrease in the PMN sequestration and the width of alveolar septa(both P<0.01),and an increase in the VV and SV(P<0.05,P<0.01).Conclusion:TanⅡA plays a protective role in LPS-induced lung injury in rats through improving hypercoagulating state,decreasing PMN-CD18 expression and alleviating migration,reducing lipid peroxidation and alleviating pathological changes.     

Altered Erythrocyte Membrane Calcium Binding in Hypertensive Rats and the Effects of Sodium Tanshinone Ⅱ-A Sulphonate on It

ＡｌｔｅｒｅｄＥｒｙｔｈｒｏｃｙｔｅＭｅｍｂｒａｎｅＣａｌｃｉｕｍＢｉｎｄｉｎｇ　ｉｎＨｙｐｅｒｔｅｎｓｉｖｅＲａｔｓａｎｄｔｈｅＥｆｆｅｃｔｓｏｆＳｏｄｉｕｍＴａｎｓｈｉｎｏｎｅⅡ－ＡＳｕｌｐｈｏｎａｔｅｏｎＩｔＷａｎｇＹｏｕｌｉｎ（王幼林）Ｔａｎ...     

Growth-inhibiting and Apoptosis-inducing Effects of Tanshinone Ⅱ A on Human Gastric Carcinoma Cells

To explore the effects of Tanshinone ⅡA on the proliferation, apoptosis and gene ex- pression of p53 and bcl-2 in human gastric carcinoma MKN-45 cells. Cell count and MTT assay were used to study the proliferation-inhibiting effect of Tanshinone ⅡA on MKN-45 cells. The effect of Tanshinone ⅡA on the cell cycle and apoptosis of MKN-45 cells were examined by propidium io- dide (PI) staining and flow cytometry. Semi-quantitative RT-PCR was used to further verify the ex- pression of p53 and bcl-2 gene after exposure to Tanshinone ⅡA in MKN-45 cells. The results showed that Tanshinone ⅡA significantly inhibited the growth and proliferation of MKN-45 cells in a dose- and time-dependent manner (P<0.05). Tanshinone ⅡA arrested MKN-45 cells in G2/M phase which led to an obvious accumulation of G2/M phase cells while decreased number of G0/G1 phase cells. This resulted in apoptosis of MKN-45 cells and the apoptosis rate was as high as 43.91% after treatment with 2.0 μg/mL TanshinoneⅡA for 96 h. It was also found that Tanshinone ⅡA up-regulated expression of p53 gene and down-regulated expression of bcl-2 gene. The cytostatic and antiproliferative effect of Tanshinone ⅡA makes it a promising anticancer agent for the treatment of gastric carcinoma.     

Inhibitory Effect of TanshinoneⅡA on TGF-β1-induced Cardiac Fibrosis

This study examined the effect of tanshinoneⅡA (TSNⅡA) on the cardiac fibrosis induced by transforming growth factor β1 (TGF-β1) and the possible mechanisms. Cardiac fibroblasts were isolated from cardiac tissues of neonatal Sprague-Dawley (SD) rats by the trypsin digestion and differential adhesion method. The cells were treated with 5 ng/mL TGF-β1 alone or pretreated with TSNⅡA at different concentrations (10–5 mol/L, 10–4 mol/L). Immunocytochemistry was used for cell identification, RT-PCR for detection of the mRNA expression of connective tissue growth factor (CTGF) and collagen type Ⅰ (COLⅠ), Western blotting for detection of the protein expression of Smad7 and Smad3, and immunohistochemistry and immunofluorescence staining for detection of the protein expression of phosphorylated Smad3 (p-Smad3), CTGF and COLⅠ. The results showed that TGF-β1 induced the expression of CTGF, COLⅠ, p-Smad3 and Smad7 in a time-dependent manner. The mRNA expression of CTGF and COLⅠ was significantly increased 24 h after TGF-β1 stimulation (P<0.01 for all). The protein expression of p-Smad3 and Smad7 reached a peak 1 h after TGF-β1 stimulation, much higher than the baseline level (P<0.01 for all). Pretreatment with high concentration of TSNⅡA resulted in a decrease in the expression of p-Smad3, CTGF and COLⅠ (P<0.01). The protein expression of Smad7 was substantially upregulated after pretreatment with two concentrations of TSNⅡA as compared with that at 2h post TGF-β1 stimulation (P<0.05 for low concentration of TSNⅡA; P<0.01 for high concentration of TSNⅡA). It was concluded that TSNⅡA may exert an inhibitory effect on cardiac fibrosis by upregulating the expression of Smad7, suppressing the TGF-β1-induced phosphorylation of Smad3 and partially blocking the TGF-β1-Smads signaling pathway.     

Effect of Chishao Chengqi Decoction(赤芍承气汤)on Endotoxin and TNF-α in Patients with Severe Hepatic Diseases

Objective:To observe the effect of Chishao Chengqi decoction (CCD) in treating severehepatopathy and its influence on serum endotoxin(ET) and tumor necrosis factor a (TNF-α), in order toexplore the possible mechanism of CCD in protecting liver cells and in preventing liver failure. Methods:Sixty patients suffering from hepatopathy were divided into the treated group and control group randomly,30 in each group. They were treated with comprehensive treatment, including hepatocyte growth-promo-ting factors, thymosin, Transmetil and albumin. CCD was given to the treated group additionally. Thetherapeutic effects were observed and the changes of some biochemical criteria, including alanine transami-nase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB) as well as such pa-rameters as prothrombin activity (PTA), serum levels of ET and TNF-α were all detected respectively be-fore treatment and after treatment. Results: In the treated group, 8 patients was clinically cured after treat-ment, 11 were markedly alleviated, 7 improved and 4 remained unchanged, while in the control group, therespective numbers were 5, 8, 8 and 9. The total effective rate of the treated group was significantly betterthan that of the control group by(P＜0.05). ET and TNF-a levels in patients were significantly higherthan the normal range before treatment, and they were lowered after treatment. Comparison of the effectbetween the two groups showed significant difference ( P＜0.05 ) , with that in the treated group betterthan that in the control group. Conclusion: CCD decoction could reduce the production and releasing of ETand TNF-α in severe hepatopathy patients, which might be one of its therapeutic mechanisms.     

Effect of Quyu Jiedu Granule (祛瘀解毒颗粒) on microenvironment of ova in patients with endometriosis

Objective:To observe the effect of Quyu Jiedu Granules(祛瘀解毒颗料,QJG) on the micro-environment of ova in patients with endometriosis(EM).Methods:Twenty EM patients who received in vitro fertilization and embryo transfer(IVF-ET) were randomized equally into a treated group and a control group. Further,20 patients who received IVF-ET due to oviduct factors were enrolled into a non-endometriosis group. The dosage of gonadotrophic hormone used,the number of ova attained,fertilization rate and clinical pregnancy...     

Effect of Sodium Tanshinone ⅡA Sulfonate on Phosphorylation of Extracellular Signal-regulated Kinasel/2 in Angiotensin Ⅱ-induced Hypertrophy of Myocardial Cells

Objective： To observe the effects of sodium tanshinone ⅡA sulfonate （STS） on angiotensin Ⅱ （Ang Ⅱ）-induced hypertrophy of myocardial cells through the expression of phosphorylated extracellular signal-regulated kinase （p-ERK1/2）. Methods： In the primary culture of neonatal rat myocardial cells, the total protein content in myocardial cells was determined by coomassie brilliant blue and the protein synthesis rate was measured by [3H]-Leucine incorporation as indexes for hypertrophy of myocardial cells. The expression of p-ERK1/2 was determined using Western blot and immunofluorescence labeling. Results： （1） The total protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ （1 μ mol/L） for 24 h; STS markedly inhibited the increment of the total protein level induced by Ang Ⅱ and the syntheses of protein. （2） After pretreatment of myocardial cells with Ang Ⅱ （1 μmol/L） for 5 min, the p-ERK1/2 protein expression was increased, with the most obvious effect shown at about 10 min; pretreatment of myocardial cells with STS at different doses （2, 10, 50μmol/L） for 30 min resulted in obvious inhibition of the expression of p-ERK1/2 stimulated by Ang Ⅱ in a dose-dependent manner. （3） After the myocardial cells were stimulated by AngⅡ （1 μ mol/L）, the immunofluorescence of ERK1/2 rapidly appeared in the nucleus. The activation and translocation process of ERK1/2 induced by Ang Ⅱ was blocked distinctly by STS. （Conclusion： STS inhibited the myocardial cell hypertrophy induced by Ang Ⅱ, and the mechanism may be associated with the inhibition of p-ERK1/2 expression.