Effect of Sodium Tanshinone Ⅱ A Sulfonate on Phosphorylation of Extracellular Signal-regulated Kinase1/2 in Angiotensin Ⅱ-induced Hypertrophy of Myocardial Cells

Objective:To observe the effects of sodium tanshinone Ⅱ A 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 Iabeling.Results:(1)The totaI protein and protein synthesis rate increased significantly in contrast to the control group after the myocardial cells were stimulated by Ang Ⅱ (1 μmol/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 μ mol/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(2,10,50 μ mol/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 Ang Ⅱ(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.     

丹参酮ⅡA对压力超负荷大鼠心肌肥厚及MAPK通路的影响

目的 探讨丹参酮ⅡA对大鼠胸主动脉缩窄诱导的心肌肥厚及丝裂原活化蛋白激酶(MAPK)信号转导通路的影响.方法 通过在右无名动脉和左侧颈总动脉之间部分缩窄胸主动脉而诱导大鼠心肌肥厚模型.将制好的模型大鼠随机分成6组:假手术组、胸主动脉缩窄组、胸主动脉缩窄组+低剂量丹参酮组(5 mg/kg)、胸主动脉缩窄组+中剂量丹参酮组(10 mg/kg)、胸主动脉缩窄组+高剂量丹参酮组(20 mg/kg)、胸主动脉缩窄组+缬沙坦组(10 mg/kg).用药8周后,B超检测心肌肥厚程度和心功能的变化;将心肌样本沿横切面切开并做苏木精-伊红染色;Western blot 法分析心肌MAPK信号蛋白表达变化.结果胸主动脉缩窄组相对于假手术组在心脏重量指数、左室重量指数、心肌纤维直径、左心室后壁及室间隔厚度均增加.而丹参酮ⅡA和缬沙坦组均可减轻上述变化的程度.Western blot结果显示:相对假手术组,模型组的p-ERK(磷酸化的细胞外信号调节激酶)和p-p38(磷酸化的p38丝裂原活化蛋白激酶)均减少,差异均具有统计学意义(均P＜0.01).相对于模型组,各丹参酮ⅡA和缬沙坦治疗组p-ERK减少,差异均具有统计学意义(均P＜0.05);丹参酮ⅡA高剂量和中剂量组,以及缬沙坦治疗组p-p38增加,差异均具有统计学意义(均P＜0.05).结论 丹参酮ⅡA通过调节MAPK通路中的蛋白表达而发挥其抑制心肌肥厚的作用.     

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.     

Growth Inhibition and Apoptosis Induction in Human Hepatoma Cells by Tanshinone Ⅱ_A

Summary:In order to study the effect of tanshinone Ⅱ_A on growth and apoptosis in human hepatomacell line BEL-7402 in vitro,the human hepatoma cell line BEL-7402 was treated with tanshinone Ⅱ_Aat various concentrations for 72 h.Growth suppression was evaluated by MTT assay;apoptosis-relat-ed alterations in morphology and biochemistry were ascertained under cytochemical staining(Hoechst33258),transmission electron microscopy(TEM),and DNA agarose gel electrophoresis.Apoptoticrate was quantified by flow cytometry(FCM).The results showed thst Tanshinone Ⅱ_A could inhibitthe growth of hepatoma cells in a dose-dependent manner,with IC_(50) value being 6.28μg/ml.Aftertreatment with 1—10 μg/ml tanshinone Ⅱ_A for 72 h,BEL-7402 cells apoptosis with nuclear chro-matin condensation and fragmentation as well as cell shrinkage and the formation of apoptotic bodieswere observed.DNA ladder could be demonstrated on DNA electrophoresis.FCM analysis showedhypodiploid peaks on histogram,and the apoptotic rates at 5     

Anti-oxidation of Tanshinone ⅡA and Prohibitin on Cardiomyocytes

Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cultured neonate rat were cultured in medium with 200 μmol/L H2O2, and the medium was supplemented with tanshinone ⅡA (1 × 10－4 mol/L) in advance for 24 h. PHB in myocardial cells was knocked down by RNA interference, and the expression level of PHB was determined by Western blotting analysis. Flow cytometric analysis was used to detect apoptosis rate, intracellular calcium concentration ([Ca2+]i), and mitochondrial membrane potential (MMP). Results H2O2-mediated cell apoptosis resulted in activation of PHB, increasing of [Ca2+]i, and decreasing of MMP. Tanshinone ⅡA profoundly inhibited myocardial cell apoptosis induced by H2O2, decreased [Ca2+]i, and increased MMP. Speci?c silence of PHB by siRNA down-regulated the expression level of PHB, increased apoptosis rate and [Ca2+]i, and decreased MMP. Conclusion The results demonstrate that tanshinone ⅡA could attenuate apoptosis induced by H2O2, and the activation of PHB induced by H2O2 is the major regulatory pathway of cyto-protective gene expression against oxidative stress.     

丹参酮ⅡA磺酸钠对高温环境下力竭运动后骨骼肌的保护作用研究

目的 分析丹参酮ⅡA磺酸钠对高温环境下力竭运动后大鼠骨骼肌的保护作用.方法 将90只大鼠分为观察组、空白组、对照组,每组30只.空白组大鼠不接受任何干预处理;观察组和对照组大鼠在高温环境下力竭运动干预,对照组大鼠在高温环境下力竭运动处理后5h经股静脉注射生理盐水8 mL/kg,观察组经股静脉注射丹参酮ⅡA磺酸钠40mg/kg.各组大鼠处死前经尾动脉采集动脉血,同时将大鼠右腿腓肠肌取下冻存.检测大鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)活性,TNF-α、IL-6、IL-1β水平,以及骨骼肌中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)水平;观察各组大鼠骨骼肌标本进行切片HE染色后的形态学变化.结果 观察组大鼠血清TNF-α、IL-6、IL-1β水平和CK、LDH活性均明显低于对照组,高于空白组,差异有统计学意义(P＜0.05).观察组大鼠骨骼肌MDA、SOD、GSH-PX水平与其他两组比较差异有统计学意义(P＜0.05).对照组大鼠骨骼肌结构紊乱,肌细胞核分布不均匀;空白组大鼠骨骼肌结构正常,肌细胞核分布均匀;观察组大鼠骨骼肌形态结构正常,但是肌细胞核分布稍显不均匀.结论 丹参酮Ⅱ A磺酸钠可以有效保护在高温环境下力竭运动后的骨骼肌.     

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.     

丹参酮ⅡA磺酸镁对大鼠急性心肌梗死的保护作用及机制

目的:探讨丹参酮ⅡA磺酸镁(Magnesium tanshinone Ⅱ A sulfonate,MTS)对急性心肌梗死的保护作用及其作用机制.方法:用冠状动脉结扎法制备大鼠急性心肌梗死模型,并将成功模型大鼠随机分为5%葡萄糖溶液对照组、丹参酮ⅡA磺酸钠组、丹参酮ⅡA磺酸镁低、中、高剂量组.结扎后5min通过尾静脉分别给予相应剂量的药物并于4h后测定大鼠心肌梗死范围以及血清和心肌组织中酶的活性.结果:与对照组比较,丹参酮ⅡA磺酸镁能剂量依赖性降低模型血清肌酸激酶(Creatine phos phokinase,CK)和乳酸脱氢酶(Lactic acid dehydrogenase,LDH)活性;减少心肌梗死范围;提高心肌组织超氧化物歧化酶(Superoxide dismutase,SOD)活性,同时降低丙二醛(Malondiadehyde,MDA)含量.结论:丹参酮ⅡA磺酸镁对急性心肌梗死有保护作用,其保护机制与抗氧自由基作用有关.     

Tanshinone ⅡA Protects against Lipopolysaccharides-lnduced Endothelial Cell Injury via Rho/Rho Kinase Pathway

Objective:To test whether tanshinone ⅡA(Tan ⅡA),a highly valued herb derivative to treat vascular diseases in Chinese medicine,could protect endothelial cells from bacterial endotoxin(lipopolysaccharides,LPS)-induced endothelial injury.Methods:Endothelial cell injury was induced by treating human umbilical vein endothelial cells(HUVECs) with 0.2 μg/mL LPS for 24 h.Y27632 and valsartan were used as positive controls.The effects of tanshinone TJ A on the LPS-induced cell viability and apoptosis rate of HUVECs were tested by flow cytometry,cell migration by transwell,adhesion by a 96-well plate pre-coated with vitronectin and cytoskeleton reorganization by immunofluorescence assay.Rho/Rho kinase(ROCK) pathwayassociated gene and protein expression were examined by microarray assay;quantitative real-time polymerase chain reaction and Western blotting were used to confirm the changes observed by microarray.Results:Tan ⅡA improved cell viability,suppressed apoptosis and protected cells from LPS-induced reductions in cell migration and adhesion at a comparable magnitude to that of Y27632 and valsartan.Tan ⅡA,Y27632 and valsartan also normalized LPS-induced actomyosin contraction and vinculin protein aggregation.A microarray assay revealed increased levels of fibronectin,integrin A5(ITG A5),Ras homolog gene family member A(RhoA),myosin light chain phosphatase,phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K,or PIP2 in Western blotting),focal adhesion kinase,vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in the damaged HUVECs,which were attenuated to different degrees by Tan ⅡA,Y27632 and valsartan.Conclusion:Tan ⅡA exerted a strong protective effect on HUVECs,and the mechanism was caused,at least in part,by a blockade in the Rho/ROCK pathway,presumably through the down-regulation of ITG A5.     

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.     

Bone Marrow-Derived Mesenchymal Stem Cells Incubated with Tanshinone IIA Aattenuates Learning and Memory Impairment Induced by β-amyloid and its Underlying Mechanisms in Rats

Objective：The present study was designed to investigate the neuroprotective effect of mesenchymal stem cells （MSC） which incubated with tanshinone IIA on β-amyloid （Aβ）-induced learning and memory impairment in rats,and further explore the underlying potential mechanisms. Methods：60 healthy male SD rats were randomly divided into 4 groups：sham-operated group,model group,MSC group,MSC+tanshinone group IIA（ n=15）.The rats of model group were injected into the hippocampal with aggregation of 5 μL Aβ25-35（ 2 μg·μL-1） to establish the model of learning and memory impairment. 1 week after surgery,the MSC were injected into the hippocampus,while the rats of model group were injected with volume-matched DMEM,instead. 2 weeks after surgery, Morris water maze （MWM） test was applied to evaluate spatial learning and memory ability of rats,then the rats were sacrifi ced. The survival status of hippocampal neurons was detected by HE and Tunel staining;the formation of hippocampal senile plaques was detected by thiofl avin S staining;the protein expression of Aβ1-42,p-Tau and AMPK in mouse hippocampus were detected by Western blot,respectively;the expression of AMPK mRNA was detected by PCR and the activity of SOD,T-AOC,GSH-PX and content of MDA in plasma by the kits.Results：Compared with sham-operated group, the mean escape latency was markedly increased and the time percentage in target quadrant showed notable decrease in model group;large number of the formation of senile plaque in the hippocampus was detected;the number of surviving neurons in hippocampus was signifi cantly decreased and the apoptosis increased;the protein expression of Aβ1-42 and p-Tau were increased;the mRNA expression and protein levels of AMPK was decreased;the activity of SOD,T-AOC,GSH-PX were decreased and content of MDA increased in plasma.However,compared with model group,the escape latency of MSC group and MSC+Tanshinone group rats was shorter,time percentage in the target quadrant and target quadrant frequency were markedly increased;moreover,the formation of senile plaque in the hippocampus was decreased;the number of surviving neurons in hippocampus was signifi cantly increased;the protein expression of Aβ1-42 and p-Tau were decreased;the mRNA expression and protein levels of AMPK was increased;the activity of SOD,T-AOC,GSH-PX were increased and content of MDA decreased in plasma.And MSC+tanshinone group was more significant than the
MSC group. Conclusion：Under the experimental conditions,MSC incubated with tanshinone ⅡA signifi cantly ameliorates spatial learning and memory impairment and reduce Aβ aggregation and tau protein phosphorylation levels induced by Aβ25-35 in rats,and its potential mechanism may be related
toanti-oxidative stress.     

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.     

The Effect of Tanshinone Ⅱ A upon the TGF-beta1/Smads Signaling Pathway in Hypertrophic Myocardium of Hypertensive Rats

SN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.     

Protective Effect of Sodium Tanshinone ⅡA Sulfonate on Injury of Small Intestine in Rats with Sepsis and Its Mechanism

Objective:To explore the protective effect of sodium tanshinoneⅡA sulfonate(STS) on small intestine injury in rats with sepsis and its possible mechanism.Methods:According to a random number table, 24 Tats were randomly divided into 3 groups:sham operation group(sham group),sepsis model group(model group) and STS treatment group(STS group),with 8 Tats in each group.A rat model of sepsis was induced by cecal ligation and puncture(CLP) for 5 h.STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestine tissue were observed under a light microscope,and the intestinal epithelial cell apoptosis was evaluated by terminal deoxynucleoddyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL) method.The expressions of Bcl-2,Bax and nuclear factorκB(NF-κB) p65 in the intestinal tissue was determined by Western blot.The levels of tumor necrosis factorα(TNF-α) and interleukin 6(IL-6) in the intestinal tissue were determined using enzyme-linked immuno-sorbent assay(ELISA). Results:Obvious injuries were observed in the intestinal tissue in the CLP group compared with the sham group. The expression of NF-κB p65 and the levels of TNF-αand IL-6 were up-regulated after CLP,the apoptosis of intestinal epithelial cells was increased after CLP,and the ratio of Bcl-2 to Bax was decreased.STS posttreatment could attenuate the injury on the intestinal tissue induced by CLP,decrease the apoptosis of intestinal epithelial cells and the levels of NF-κB p65,TNF-αand IL-6,and increase the ratio of Bcl-2 to Bax.Conclusion: STS can protect the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of intestinal epithelial apoptosis and the reduction of activation of inflammatory cytokines.     

Sclerosing Mesenteritis: A Report of 5 Cases

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

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丹参酮ⅡA对乳腺癌抑制作用的体内实验研究

目的 观察丹参酮ⅡA在乳腺癌裸鼠模型体内的抗肿瘤作用,并初步探讨其机制.方法 建立雌激素受体阳性细胞株MCF-7和雌激素受体阴性细胞株MDA-MB-231的裸鼠乳腺癌模型.分组分别以腹腔注射丹参酮ⅡA 30 mg/kg 4周;他莫西芬灌胃1 mg/kg 4周和溶剂对照处理.取瘤体标本称重、流式细胞法分析肿瘤细胞凋亡情况、免疫组化法测量标本的p53、bcl-2、cerbB-2的表达并行半定量分析观察变化情况.结果 在MCF-7组丹参酮ⅡA体积抑瘤率33.64%、瘤重抑瘤率32.24%;在MDA-MB-231组,丹参酮ⅡA体积抑瘤率达38.34%,瘤重抑瘤率39.82%,两种模型与他莫西芬组和溶剂对照组比较,差异均具有统计学意义(P＜0.05).流式细胞分析显示,丹参酮ⅡA在两种模型中均可上调肿瘤细胞凋亡分数(MCF-7组48.31%±5.84%、MDA-MB-231组50.25%±5.03%),较对照组及他莫西芬组差异均有统计学意义(P＜0.05);免疫组化结果 显示,在两种细胞株瘤体中,丹参酮ⅡA组与溶剂对照组比较,p53和bcl-2表达下调(P＜0.05),cerbB-2的表达强度未见明显差异(P＞0.05).结论 丹参酮ⅡA在乳腺癌MCF-7和MDA-MB-231细胞株裸鼠模型体内有明显的抑制肿瘤生长作用,且作用强于他莫西芬.其机制可能与诱导凋亡、下调bcl-2和p53的表达水平有关,而与cerbB-2的表达水平无关.