PPARγ激活剂rosiglitazone对大鼠慢性阻塞性肺疾患的防治作用

目的:评价高亲和力过氧化物酶体增生物激活的受体γ(PPARγ)激动剂rosiglitazone对大鼠慢性阻塞性肺疾患(COPD)的防治作用。方法:在第1和14d每只大鼠气管内滴入大肠杆菌脂多糖(LPS)200μg(0.2mL),第2-28d(第14d除外)每天烟熏40min,每只经食管灌入rosiglitazone0.02mg。第29d处死大鼠,取肺组织检查形态学改变;取血清测血糖、血脂变化;取脾细胞测对LPS的反应。结果:模型组大鼠肺泡明显扩张、有的肺泡融合形成较大囊腔。Rosiglitazone处理的大鼠肺体积较小,显微镜下可见肺泡扩张不明显,肺泡间隔较完整,肺泡直径为(134.997±17.568)×10-3μm,低于模型组大鼠(308.362±111.913)×10-3μm,高于正常对照大鼠(5.116±1.673)×10-3μm(P<0.01)。血糖、甘油三酯、胆固醇和低密度脂蛋白含量均无明显变化。Rosiglitazone抑制正常大鼠、模型大鼠和rosiglitazone处理的大鼠脾细胞对LPS的增殖反应。结论:Rosiglitazone可减轻熏烟和气管内滴入LPS诱导的肺气肿。

Effect of rosiglitazone on rabbit model of myocardial ischemia-reperfusion injury

To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion(I/R) injury.Methods:A total of 48 male Japanese white big-ear rabbits were randomly divided into control group(A),I/R group(B),low dose of rosiglitazone group(C),high dose of rosiglitazone group(D).Plasma concentration of and also reduced the concentration of plasma serum creatine kinase(CK),CK-MB.high-sensitivity C-reactive protein(hsCRP).ultrasuperoxide dismutase(SOD),malondialdehyde(MD.A).lactic acid glutathione skin peroxidase (C-SH-PX).nitric oxide(NO)and endothelin(ET) were measured 1 h later after I/R.Twenty-four hours after I/R the hearts were harvested for pathological and ultrastructural analysis.Area of myocardial infarction were tested.Results:Plasma concentration of CK,Ck-MB.hsCRP,NO. MDA and ET were decreased in C,D group compared with group B.Plasma concentration of T-SOD and GSH-Px were increased significantly in C.D group compared with group B.Compared with group B.pathological and ullraslructural changes in C and D group were slightly.There was significant difference in myocardial infarction area between group C.D and group B(P【0.05). Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B. Rosiglitazone may protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,and improve endothelial function.

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-y in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally rejected with methylprednisolone （30 mg/kg） and rosiglitazone （2 mg/kg） at 1 hour after injury, and methylprednisolone （15 mg/kg） at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better pro- moted recovery of neurological function after injury.

A new look at auranofin,dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases

Neurodegenerative disorders including Alzheimer＇s disease are characterized by chronic in- flammation in the central nervous system. The two main glial types involved in inflammatory reactions are microglia and astrocytes. While these cells normally protect neurons by providing nutrients and growth factors, disease specific stimuli can induce glial secretion of neurotoxins. It has been hypothesized that reducing glia-mediated inflammation could diminish neuronal loss. This hypothesis is supported by observations that chronic use of non-steroidal anti-inflamma- tory drugs （NSAIDs） is linked with lower incidences of neurodegenerative disease. It is possible that the NSAIDs are not potent enough to appreciably reduce chronic neuroinflammation after disease processes are fully established. Gold thiol compounds, including auranofin, comprise an- other class of medications effective at reducing peripheral inflammation. We have demonstrated that auranofin inhibits human microglia- and astrocyte-mediated neurotoxicity. Other drugs which are currently used to treat peripheral inflammatory conditions could be helpful in neu- rodegenerative disease. Three different classes of anti-inflammatory compounds, which have a potential to inhibit neuroinflammation are highlighted below.

PPARγ activator,rosiglitazone:Is it beneficial or harmful to the cardiovascular system?

Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with typeⅡdiabetes.Rosiglitazone exerts its glucose-lowering effects by improving insulin sensitivity.Data from various studies in the past decade suggest that the therapeutic effects of rosiglitazone reach far beyond its use as an insulin sensitizer since it also has other benefits on the cardiovascular system such as improvement of contractile dysfunction,inhibition of the inflammatory response by reducing neutrophil and macrophage accumulation,and the protection of myocardial injury during ischemic/reperfusion in different animal models.Previous clinical studies in typeⅡdiabetes patients demonstrated that rosiglitazone played an important role in protectingagainst arteriosclerosis by normalizing the metabolic disorders and reducing chronic inflammation of the vascular system.Despite these benefits,inconsistent findings have been reported,and growing evidence has demonstrated adverse effects of rosiglitazone on the cardiovascular system,including increased risk of acute myocardial infarction,heart failure and chronic heart failure.As a result,rosiglitazone has been recently withdrawn from EU countries.Nevertheless,the effect of rosiglitazone on ischemic heart disease has not yet been firmly established.Future prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone in patients with heart disease.

Rosiglitazone防治慢性支气管炎肺气肿的作用机制研究

目的:探讨Rosiglitazone防治慢性支气管炎肺气肿的作用机制。方法:(1)Rosiglitazone对烟熏和气管内滴入LPS大鼠肺组织氧化应激的调节作用:随机将SD大鼠分为3组:(a)慢性支气管炎/肺气肿模型组;(b)Rosiglitazone处理组;(c)对照组,不进行任何处理。测定3组大鼠肺组织上清中丙二醛(MDA)、超氧化物歧化酶(SOD)和一氧化氮(NO)含量。(2)Rosiglitazone对LPS刺激的脾脏巨噬细胞的NO分泌与MMP-9表达的调节作用:制作以上3组大鼠脾细胞悬液,取上清检测NO含量,结果表明加入Rosiglitazone,NO含量增加。48h后收集细胞调浓度至5×106/ml,加trizol1ml提取细胞总RNA用RT-PCR方法检测MMP-9表达。结果:(1)Rosiglitazone处理组大鼠肺组织中MDA含量较模型组明显降低。Rosiglitazone处理组大鼠肺组织中SOD含量较模型组明显增加。Rosiglitazone处理组大鼠肺组织中NO含量较模型组显著增加。(2)RT-PCR结果显示,加入Rosiglitazone使MMP-9表达降低;单用Rosiglitazone刺激脾脏巨噬细胞中MMP-9的表达与正常脾脏巨噬细胞中MMP-9的表达无显著性差异。结论:PPARγ激动剂Rosiglitazone可明显减轻烟熏和气管内滴入IPS所致慢性支气管炎/肺气肿大鼠肺组织的氧化应激反应,并提高其抗氧化能力,抑制脾脏巨噬细胞:MMP-9表达的作用,这些变化都有助于减轻吸烟和LPS所致的肺组织损伤。这些结果提示Rosiglitazone等PPARγ激动剂对防治慢性支气管炎/肺气肿有一定作用。

Effect of Rosiglitazone Maleate on Inflammation Following Cerebral Ischemia/Reperfusion in Rats

In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and inter- leukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swell- ing (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflam- matory response after ischemia-reperfusion in this model.

Significance of Rosiglitazone Inhibiting TLR4 Expression in Partial Hepatic Ischemia/Reperfusion of Mice

The effect of rosiglitazone as the ligand of peroxisome proliferator-activated receptor γ （PPARγ） inhibiting the TLR4 expression in ischemic lobes in partial hepatic ischemia/reperfusion injury （IRI） in BABL/C mice and the action of rosiglitazone inhibiting the TLR4 receptor-mediated inherent immune response were investigated. The model of the mouse partial hepatic ische- mia/reperfusion injury was established. All the animals were randomly divided into 3 groups： rosiglitazone group, vehicle （dimethylsulphoxide, DMSO） group and sham operation group. The hepatic samples were collected when mice were sacrificed 0, 2, 4 and 6 h after reperfusion following 1 h ischemia to analyze the acute phase of hepatic IRI. The dynamic expression of TlR4 mRNA was de- tected quantitatively by real-time-PCR, and the levels of TNF-α, IL-10 and ALT in portal vein were determined in all groups. After restoration of blood supply, the expression of TLR4 mRNA in ischemic lobes was detected in 0, 2, 4 and 6 h after reperfusion following 1 h ischemia in rosiglitazone group and vehicle group. The most intensive expression of TLR4 mRNA was present at 4 h after reperfusion in ischemic lobes in vehicle group. As compared with vehicle group, the expression of TLR4 mRNA in ischemic lobes in rosiglitazone group was significantly decreased at 4 h after reper- fusion. The level of IL-10 in portal vein was markedly up-regulated in rosiglitazone group as compared with vehicle group. Contrarily, the levels of TNF-α and ALT in portal vein were markedly down-regulated in rosiglitazone group as compared with vehicle group at every time point in mouse partial hepatic IRI model. Rosiglitazone could alleviate the hepatic IRI by inhibiting TLR4 receptor-mediated inherent immune response.

Rosiglitazone prevents gliosis,oxidative/nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats

Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods 24 male Wistar rats were randomly divided into sham operated group,model group and rosiglitazone group.The model of Alzheimer's was induced by injection with ICV 10% STZ bilaterally,on day 1 and 3(3 mg·kg-1).The rats were treated with rosiglitazone(2 mg·kg-1,p.o.)for a consecutive 21 days,once a day,beginning 7 days prior to STZ injection.The learning and memory behavior was assessed using Morris water maze task and Y-maze 21 d after ICV STZ injection.Malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)levels and nitrotyrosine immunoreactivity in brain were estimated as parameters of oxidative/nitrative stress.Brain acetyl cholinesterase(AchE)activity was measured by EllMann's method and activated microglia and astrocytes were detected by immunohistochemistry.Results ICV STZ injection resulted in a severe deficit in spatial learning and memory associated with increased MDA level(+69.5%)and nitrotyrosine immunoreactivity(+23.7%),decreased SOD activity(-29.2%)and GSH(-25.1%)in brain.It also showed the activated microglia and astrocytes in the cortex and hippocampal CA1 region and a significant decrease in acetylcholinesterase activity(-40.2%).Compared with model group,chronic administration of rosiglitazone significantly shorten the escape latency time from the third day in place navigation test,increase the number of passing through primary flat place in spatial probe test in Morris water maze test,and decrease the error times in Y-maze test(P<0.05 or P<0.01).In addition,it also prevented the glial changes,decreased the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity in cortex(P<0.05),but had no effect on SOD activity in cortex.Conclusions Rosiglitazone has a neuroprotective role against streptozotocin-induced cognitive impairment and associated oxidative/nitrative stress.

Effect of Rosiglitazone on Endocrine, Metabolism and Ovulatory Performance in Patients with Polycystic Ovary Syndrome and Insulin Resistance

The effect of rosiglitazone on endocrine, metabolism and ovulatory performance in the paitents with polycystic ovary syndrome(PCOS) and insulin resistance was investigated. Twenty-five patients diagnosed as having polycystic ovary syndrome (PCOS) combined with insulin resistance were treated with rosiglitazone for 12 weeks. Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), androstenedione (A), sex hormone binding globulin (SHBG), insulin and glucose concentration, total cholesterol, triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholestero (LDL-C), apolipoprotein A, apolipoprotein B levels and ovulatory performance were determined. The results showed that after treatment serum insulin levels was decreased significantly (P<0.01). The HDL-C was increased while LDL-C decreased significantly (P<0.05, P<0.01). The serum LH, T, A concentrations and the ratio of LH/FSH were decreased, while SHBG levels increased significantly (P<0.01). The ovulation rate during clomiphene citrate therapy was 72 %, significantly higher than that before treatment. It is likely that reduction of hyperinsulinemia that is produce by rosiglitazone may effectively improve the endocrine, metabolism and ovulatory performance in the patients with PCOS and insulin resistance.

The Impact of a Drug Safety Warning on Discussions between Doctors and Their Patients;the Case of Rosiglitazone

The goal of this study was to track the influence of a highly publicized report on discussions between doctors and their patients and prescribing decisions made in response to concerns about potential medication adverse side effects. This was a retrospective analysis of a primary care network’s electronic medical record database. From a diabetes registry of 12, 246 patients, 329 were identified as taking rosiglitazone prior to the June 14, 2007 release of an article in the New England Journal of Medicine;the article suggesting an increased risk of myocardial events. The entire content of all office visits, telephone messages, and medication lists for each patient were reviewed over a 2-year period subsequent to the article’s publication. Doctor/patient discussions regarding concerns for rosiglitazone were catalogued including the physician’s treatment recommendations. There were documented discussions on rosiglitazone’s potential adverse side effects for 64 patients;19.5 percent of this population. All of the discussions occurred between June 15 and October 30, 2007. Of the entire group, 59.3 percent (N = 195) remained on rosiglitazone. For those advised to continue rosiglitazone, the provider indicated that he/she wanted more data before determining if the drug was not safe or discounted the validity of the safety concerns. For those advised to discontinue rosiglitazone, 112 (83.6 percent) were placed on pioglitazone. An article suggesting potential adverse effects of rosiglitazone resulted in a documented discussion in 19.5 percent of patients on this medication. These findings suggest an awareness of this publication by patients, presumably derived from media reports. However, an awareness of this concern did not result in a substantial change in practice.The majority of patients remained on rosiglitazone. The content of these discussions suggest that most physicians’ recommended waiting for more published data before considering a change. While many factors influence physician’s prescribing behavior, this study demonstrates how a highly publicized report influences the doctor/ patient dialogue.

Anti-hypertensive effects of rosiglitazone on renovascular hypertensive rats:role of oxidative stress and lipid metabolism

This study investigated the anti-hypertensive mechanismof rosiglitazone in renovascular hypertensive rats,and examined its relationship to oxidative stress and lipid metabolism. The renovascular hypertension was induced by stenosis of the left renal artery. Four groups of rats were selected： control,induced untreated,rosiglitazone（ 20 mg / kg） and captopril（ 10 mg / kg）. After 14 d of administration,compared with induced untreated group,rosiglitazone group reduced the renovascular hypertensive rats ＇ systolic blood pressure and diastolic blood pressure,and decreased total cholesterol（TCH）,triglyceride（TG）,angiotensin II（ Ang II） and angiotensin receptor（ AT1） levels（ P ＆lt; 0. 05）. Meanwhile,rosiglitazone remarkably decreased the levels of malondialdehyde（ MDA） and hydrogen peroxide（ H2O2） while improved the levels of supperoxide dismutase（ SOD） and reduced glutathione（ GSH）. These results suggested that rosiglitazone could effectively decreased the blood pressure in renovascular hypertensive rats,and this might be performed by regulating the activity of angiotensin and the lipid metabolismand improving the oxidative stress.

Rosiglitazone uppresses lipopolysaccharide-induced matrix metalloproteinase-2 activity in rat aortic endothelial cells via rasMEK1/2 signaling

ix metalloproteinase(MMPs) plays a key role in the pathogenesis of chronic inflammatory disease,such as atherosclerosis.Among MMPs,MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions.Peroxisome proliferator activated receptor-gamma(PPARg) ameliorates oxidative stress and the inflammatory response.The aim of the present study was to evaluate the effect of Rosiglitazone on Lipopolysaccharide(LPS)-induced MMP-2 activation as well as its possible mechanism.LPS-induced MMP-2 activity was inhibited by Rosiglitazone(PPARg agonist) in the rat aortic endothelial cells(RAEC).LPS-induced MMP-2 activation was diminished no matter exposure to NF-kB Activation Inhibitor II(JSH-23)or Ras inhibitor,farnesylthiosalicylic acid(FTS). Further study shows that LPS-induced activation of Phospho-Rho A and Phospho-MEKl/2 were significantly inhibited by Rosiglitazone.The activation of NF-kB p65 in the nuclear extract of cells was also significantly suppressed by Rosiglitazone, moreover,the expression of NF-κB p65 was partly activated by GW9662(PPARg antagonist).NF-kB DNA binding activity was also demolished by Rosiglitazone.In summary,our data showed that PPARg agonist,Rosiglitazone suppresses LPS-activated MMP-2 secretion via Ras-MEK1/2 signaling pathways and NF-kB activation.PPARg agonist and Ras-MEK1/2 pathway may be another potential therapeutic target for the disease induced by chronic inflammation.

007 Rosiglitazone治疗老年人2型糖尿病疗效与安性评价

在一般人群中，伴随年龄增长2型糖尿病发病率明显增加。因而选择理想药物治疗老年人2型糖尿病尤显重要。本文拟就选用Rosiglitazone(强效乙基噻唑烷类药物之一)单一治疗2型糖尿病的8项多中心随机单盲对照试验结果进行了汇总分析，以期评价其治疗老年与非老年人2型糖尿病疗效及安全性的差异。对象与方法 3127例2型糖尿病患者，先期剔除伴有严重肾病、心绞痛、心功能不全、糖尿病肾病、肝病、糖尿病酮症史、长期使用胰岛素史和伴其它严重疾病者后，分为随机单盲服用：Rosiglitazone(4～8mg／d)的治疗组2526例，其中<70岁非老年人2099例，≥70岁老年人427例：或仅服安慰剂的对照组60l例，其中<70岁非老年人497例，≥70岁老年人104例，疗程人均26周。尔后观察分析两组间以及老年与非老年人药物疗效和安全性的差异。结果两组间糖尿病临床特点及年龄均无明显差异。与非老年人相比，老年人病程较长、体重较轻、并发腹疝、关节病、白内障、高血压、骨关节炎、前列腺疾病者均明显居多。与用药前相比，用药26周后，治疗组无论老年与非老年人，其血红蛋白Alc及空腹血糖均较对照组同龄者明显降低；且治疗组均能良好耐受用药。治疗组与对照组用药期间罹发1次以上恶性事件者非老年人分别68．8％与62．2％、老年人分别69．8％与62．5，多能坚持用药，被迫停药者非老年人分别仅6．1％与7．8％、老年人分别仅6．8％与9．6％；最常见的药物毒副作用为浮肿、贫血及体重增加老年人稍示增多，诱发心衰或高血糖症均罕见。治疗组与对照组，因药物无效而被迫停药者非老年人分别6．7％与13．9％、老年人分别8．2％与9．6％。讨论以上分析表明，选用Rosiglitazone治疗老年人2型糖尿病，无论降糖药效及其安全性均与非老年人相仿。

豹蛙酶与rosiglitazone有协同抗癌作用

美国Vermont大学的研究人员发现，Alfacell公司开发的两栖动物卵母细胞／早期胚胎的核糖核酸酶豹蛙酶和降糖药rosiglitazone有协同抗癌作用，可使磷脂酰肌醇3激酶下游蛋白Fra—1和Survivin表达增加的癌细胞生存力降低，凋亡增加。已在多种癌细胞系中观察到肯定的活性，包括肺、乳腺、前列腺和卵巢癌。

Rosiglitazone reduces fatty acid translocase and increases AMPK in skeletal muscle in aged rats： a possible mechanism to prevent high-fat-induced insulin resistance

Background As an agonist of peroxisome proliferator-activated receptor-gamma （PPARy）, rosiglitazone can prevent acute fatty acid-induced insulin resistance in rats, however, the precise mechanisms by which rosiglitazone alleviates insulin resistance induced by high-fat diet need to be further investigated.Methods Wistar rats aged 23-24 weeks were divided into three groups： （1） aged control group （OC）, （2） high-fat diet （HF） group and （3） high-fat diet plus rosiglitazone maleate tablets （HF＋Rosi） treatment group （n=20 in each group）. Insulin sensitivity was evaluated by conscious hyperinsulinemic-euglycemic clamp technique. mRNA levels of fatty acid translocase （FAT/CD36）, AMP-activated protein kinase α1 （AMPKα1）, AMPKα2 and acetyl CoA carboxylase （ACC） of rat skeletal muscle were determined using real-time PCR, while muscle camitine palmitoyltransferase-1 （CPT-1β） was determined using semi-quantitative PCR. Protein expression levels of FAT/CD36, AMPK phosphorylation （reflecting AMPK activity）, P-ACC （inversely related with ACC activity） and muscle CPT-1M in rat skeletal muscles were measured using Western blotting.Results Aged rats fed by diet rich in fat for more than 8 weeks led to significant increases of plasma lipids, skeletal muscle intramuscular triglyceride and long-chain fatty acyl-CoA （LCACoA） compared to aged rats fed by normal chow diet （OC） （P 〈0.05）, which might correlate with the lower （reduced by 42.4%） whole body insulin sensitivity in HF rats. FAT/CD36 protein concentrations and mRNA levels increased in untreated HF aged rats （P 〈0.01） and high-fat diet induced a significant decrease in P-AMPK, P-ACC, CPT-1M protein concentrations and AMPKα2 and CPT-1β mRNA levels in rat skeletal muscles （P 〈0.05）. No change in AMPKα1 mRNA levels was observed in the HF group.Conclusion High-fat diet in aged rats results in a lipid accumulation and subsequent insulin resistance, while rosiglitazone can alleviate the insulin resistance by reducing fatty acid uptake as well as enhancing lipometabolism.

Metformin versus metformin plus rosiglitazone in women with polycystic ovary syndrome

Background Hyperinsulinemia and insulin resistance are present in the majority of women with polycystic ovary syndrome （PCOS）. Both metformin and rosiglitazone can improve the ovulation and endocrine disorders of the patients. How about the combination of the two？ It is rarely reported. This study aimed to compare the therapeutic efficacy of metformin versus metformin plus rosiglitazone in patients with PCOS.Methods Fifty-eight women with PCOS were randomly assigned to two groups. Metformin group （29） was treated with metformin mono-therapy and metformin plus rosiglitazone group （29） was treated with metformin plus rosiglitazone for 6 months. Treatment was discontinued once pregnancy was diagnosed.Results Fasting insulin, postprandial insulin, the homeostatic model assessment of insulin resistance （HOMA-IR）, luteinizing hormone （LH）, triglyceride, lower density cholesterol and testosterone level decreased significantly in both groups （P 〈0.05）. Metformin plus rosiglitazone had a better effect than metformin mono-therapy. Body mass index decreased by 7.8% in metformin group while no significant change in metformin plus rosiglitazone group. There were eight pregnancies, six in rnetformin plus rosiglitazone group （one abortion） and two in metformin group. There was no congenital anomaly at birth and seven infants developed well at one year＇s follow-up.Conclusions Metformin can improve insulin resistance and imbalance of endocrine hormones. Metformin plus rosiglitazone has a more pronounced therapeutic effect and achieved more pregnancies than mono-therapy with metformin. The use of metformin and rosiglitazone before pregnancy has no obvious side effect on the development of the infants. Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin.