牛磺酸对糖尿病大鼠视网膜谷氨酸转运蛋白mRNA表达的影响

目的探讨牛磺酸对糖尿病大鼠视网膜超微结构及谷氨酸转运蛋白(GLAST)mRNA表达的影响。方法糖尿病大鼠接受牛磺酸处理3个月后,用RT-PCR技术检测对视网膜GLAST mRNA表达的影响,透射电镜观察视网膜超微结构的变化。结果糖尿病大鼠成模1个月始,视网膜中GLAST mRNA表达减弱,且随病程延长表达下降显著视网膜膜盘排列紊乱,线粒体肿胀;牛磺酸干预能上调糖尿病视网膜GLAST mRNA的表达,并使视网膜膜盘排列明显变整齐,线粒体肿胀减轻。结论牛磺酸通过上调GLAST mRNA的表达改善糖尿病大鼠视网膜GLAST功能,降低谷氨酸兴奋毒性,从而保护神经视网膜。     

塞来昔布对实验性糖尿病大鼠早期视网膜病变的影响

目的研究塞来昔布对糖尿病（DM）大鼠视网膜血管内皮生长因子（VEGF）表达及视网膜超微结构的影响。方法将40只Wistar大鼠用链脲佐菌素（STZ）腹腔注射制成DM大鼠模型,随机分成DM组（n=20）和塞来昔布灌胃组（n=20）。另15只正常大鼠为正常对照组。3个月后处死全部大鼠,取视网膜进行透射电镜观察,应用免疫组化检测视网膜VEGF蛋白表达。结果塞来昔布灌胃组视网膜内皮细胞、神经节细胞凋亡较DM组明显减轻。正常对照组视网膜VEGF免疫组化反应阳性弱,VEGF蛋白表达量低;DM组视网膜VEGF免疫组化反应呈强阳性,VEGF蛋白表达增高（P〈0.01）;塞来昔布灌胃组VEGF免疫组化反应阳性减弱,VEGF蛋白表达降低（P〈0.01）。结论塞来昔布能够抑制STZ诱导的DM大鼠视网膜VEGF蛋白表达,并减轻视网膜超微结构损害。     

胰岛素样生长因子Ⅰ受体mRNA与实验性糖尿病视网膜病变的初步研究

目的：探讨胰岛素样生长因子Ⅰ受体（IGF－ⅠR）mRNA在糖尿病视网膜病变（DR）发病中的作用。方法：复制糖尿病大鼠模型，分别于成模后3个月和6个月时经光镜和透穿电镜观察视网膜的形态学改变。应用原位杂交技术对IGF－ⅠR mRNA在视网膜上的表达情况进行动态观察与分析。结果：（1）IGF-ⅠRmRNA在正常大鼠视网膜节细胞层及内核层均有表达（约占5％）；（2）糖尿病大鼠视网膜内IGF－ⅠRmRNA表达显著增强，3个月病程表达量约占15％。6个月病程表达量约占18％；（3）经胰岛素治疗的糖尿病大鼠视网膜上IGF－ⅠRmRNA表达明显少于相同病程模型组。3个月治疗组表达量约8％，6个月治疗组表达量约占10％。结论：IGF－ⅠRmRNA随糖尿病大鼠病程延长，病情加重，表达量增加，随胰岛素治疗,表达量减少，IGF－ⅠRmRNA表达量的变化很可能是DR发生，发展的重要因素。     

罗格列酮对糖尿病大鼠心肌纤维化及炎症因子表达的影响

目的探讨盐酸罗格列酮（RGZ）对糖尿病（DM）大鼠心肌纤维化及炎症因子表达的影响。方法30只实验大鼠分正常对照（NC）组（n=8）、DM组（n=11）、RGZ组（n=11）,用药12周。测血糖、体重、HbA1C、心脏重量、左室心肌胶原含量、血清单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子α（TNF-α）水平、心肌结缔组织生长因子（CTGF）表达的变化,观察心肌细胞超微结构。结果与NC组相比,DM组大鼠左室心肌组织胶原含量明显升高（16％±2％vs10％±3％,P〈0．01）,存在心肌间质纤维化;DM组MCP-1、TNF-α水平、心肌CTGF表达明显升高（分别为34．2±3．9vs17．5±2．8,9．8±2．5vs5．0±1．4,154士19vs98±16,P均〈0．01）;RGZ治疗后,左室心肌组织胶原明显下降（12％±3％w16％±2％,P〈0．05）,MCP-1、TNF-α水平及心肌CTGF表达明显降低（分别为20．2±3．2讲34．2±3．9,P〈0．01;6．5±2．12759．8±2．5,P〈0．01;121±16vs154±19,P〈0．05）。结论RGZ能明显抑制DM大鼠心肌间质纤维化,并能降低MCP-1、TNF-α水平及心肌CTGF的蛋白表达。     

Notch-1及Delta样配体4在糖尿病大鼠早期视网膜中的表达

目的探讨糖尿病早期大鼠视网膜中Notch-1与Delta样配体4(Dll-4)的表达变化,及其与血管内皮生长因子受体-2(VEGFR-2)的关系。方法健康雄性成年大鼠60只,分为正常对照(NC)组,糖尿病1个月(DM 1 m)组、2个月(DM 2 m)组及3个月(DM 3 m)组。免疫组织化学法和RT-PCR检测视网膜中Notch-1、Dll-4、VEGFR-2的表达。结果免疫组织化学结果显示,糖尿病大鼠Notch-1、Dll-4、VEGFR-2在视网膜中染色范围较正常大鼠广。RT-PCR结果显示,DM 2 m组、DM 3 m组Dll-4mRNA表达较NC组升高(P0.05),DM 1 m组、DM 2 m组、DM 3 m组Notch-1 mRNA、VEGFR-2mRNA表达较NC组升高(P0.05)。Dll-4 mRNA与VEGFR-2及Notch-1呈正相关(r=0.80、0.89,P0.01),Notch-1与VEGFR-2 mRNA表达呈正相关(r=0.88,P=0.00)。结论糖尿病大鼠早期的视网膜中,Notch-1、Dll-4表达升高,与VEGFR-2表达基本一致,表明糖尿病早期Notch信号通路参与调控视网膜的变化,这种调控作用也许和VEGF通路有关。     

螺内酯对2型糖尿病大鼠肾脏紧张素转换酶2和细胞间黏附分子表达的影响

目的观察螺内酯对T2DM大鼠肾脏紧张素转换酶2（ACE2）和细胞间黏附分子（ICAM-1）表达的影响,以探讨其对糖尿病肾脏病变的保护作用。方法用高脂高糖饲料喂养大鼠2个月后,腹腔注射30mg／kg STZ制备糖尿病大鼠模型,分为正常对照（NC）组、糖尿病（DM）组、螺内酯治疗（R）组,检测第16周FBG、Cr、24hUAER、肾重／体重（×10^-3）;并用免疫组化和RT-PCR的方法检测16周后大鼠肾脏ACE2和ICAM-1表达的改变。结果第16周末DM、R组各项比较,差异无统计学意义（P〉0．05）,但均高于NC组（P均〈0．01）;R组ACE2水平高于DM组（P〈0．01）,ICAM-1水平低于DM组（P〈0．05）。结论螺内酯通过增加肾脏组织ACE2的表达、降低ICAM-1的表达而发挥保护肾脏的作用。     

通络方药对2型糖尿病大鼠心肌和主动脉iNOS基因表达的影响

目的观察通络方药（Tongluo Recipe,TLR）对2型糖尿病大鼠心肌和主动脉诱导型一氧化氮合酶（iNOS）基因表达的影响,探讨TLR在2型糖尿病（type 2 diabetes,T2DM）的干预作用和应用价值。方法30只雄性健康清洁级SD大鼠随机分为3组：正常对照组、T2DM组、T2DM＋TLR干预组,每组10只。T2DM＋TLR干预组大鼠TLR按0．4g·kg^-1·d^1剂量灌胃,1次,d,持续给药12W后处死取心肌、主动脉组织待测。利用实时定量逆转录多聚酶链反应（RT-PCR）方法测定各组大鼠心肌、主动脉诱导型一氧化氮合酶iNOS的基因表达水平。结果与正常对照组比较,2型DM组大鼠心肌和主动脉iNOS的mRNA表达明显降低（P〈0．01、P〈0．05）,而T2DM＋TLR干预组大鼠心肌和主动脉iNOS的mRNA表达较T2DM组明显升高（P〈0．01）。结论TLR可以增加T2DM大鼠心肌、主动脉iNOS的mRNA表达,从而增加NO合成,可能对T2DM具有防治意义。     

罗格列酮对2型糖尿病并发非酒精性脂肪肝大鼠肝脏解偶联蛋白-2表达的影响

目的观察罗格列酮对2型糖尿病（T2DM）并发非酒精性脂肪肝（NAFLD）大鼠肝脏解偶联蛋白-2（UCP-2）表达的影响,探讨其防治T2DM并发NAFLD的部分作用机制。方法高脂高糖饮食结合小剂量链脲佐菌素（STZ）腹腔注射建立T2DM并发NAFLD大鼠模型,将成模大鼠随机分为模型组、罗格列酮治疗组,每组各16只,并设立正常对照组。治疗组给予罗格列酮3 mg/（kg.d）灌胃治疗。于实验第16（治疗后8周）、20周（治疗后12周）末分批处死大鼠,检测肝功能、空腹血糖、血脂和血清胰岛素水平,光镜下观察大鼠肝脏组织学形态,分别以免疫组织化学法和逆转录-聚合酶链反应（RT-PCR）法检测肝组织UCP-2蛋白和UCP-2mRNA的表达情况。结果与正常组相比,模型组大鼠血清转氨酶、空腹血糖、血清胰岛素及血脂水平均明显升高,胰岛素敏感指数明显下降（P均〈0.01）,肝脏出现不同程度脂肪变性,肝组织UCP-2蛋白和UCP-2 mRNA表达增高,以20周末最为明显。在16周末（治疗后8周）和20周末（治疗后12周）,治疗组大鼠血清转氨酶、血糖、血清胰岛素及血脂水平均有改善,胰岛素敏感指数明显升高,肝细胞脂肪变性明显减轻,肝组织UCP-2蛋白和UCP-2 mRNA表达明显下降,与模型组比较差异均有统计学意义（P〈0.01）。结论 T2DM并发NAFLD大鼠肝组织UCP-2表达增强,罗格列酮可以调控T2DM并发NAFLD大鼠肝脏UCP-2 mRNA和UCP-2蛋白的适度表达,这可能是其治疗T2DM并发NAFLD的分子机制之一。     

阿托伐他汀对糖尿病大鼠内皮祖细胞及视网膜病变影响的研究

目的探讨他汀类药物对糖尿病大鼠循环内皮祖细胞（EPCs）及视网膜病变的影响及作用机制。方法成年Wistar大鼠150只,随机分为2组。正常对照组（阴性组）,糖尿病组（阳性组）。注射链尿佐菌素（STZ）,造糖尿病大鼠模型。将糖尿病大鼠再随机分为3组：低剂量组（他汀10mg／Kg·d）,高剂量组（他汀20mg／Kg·d）,单纯糖尿病组。灌胃给药,对照组及单纯糖尿病组给予等量生理盐水。大鼠分别于3个月,6个月时按比例随机处死。取动脉血检测EPCs数量、取眼球固定后观察视网膜血管内皮生长因子（VEGF）蛋白表达情况。结果糖尿病大鼠造模成功率81％。3个月及6个月时,低剂量组存活率均较高剂量组及单纯糖尿病组有所增加（P〈0．05）。他汀类药物促进EPCs数量上升,低剂量组与对照组、糖尿病组、高剂量组比较,3个月及6个月时各组间均有统计学意义（P〉0．05）,高剂量组与对照组及糖尿病组比较无统计学差异（P〈0．05）。不同剂量的他汀类药物对视网膜VEGF蛋白表达情况：糖尿病组VEGF免疫阳性表达最强,高剂量组VEGF免疫阳性表达比糖尿病组减弱,低剂量治疗组VEGF免疫阳性表达最低。结论他汀类药物能够促进EPCs数量增加。小剂量他汀类药物可抑制糖尿病大鼠视网膜VEGF表达,减缓视网膜病变进展;并降低糖尿病大鼠的死亡率。     

胡芦巴多糖A2对糖尿病大鼠肾脏ECM的影响

目的探讨胡芦巴多糖A2对糖尿病（DM）大鼠肾脏结构和功能改变的影响,以阐述结缔组织生长因子（CTGF）在DM肾病（DN）发生发展中的可能机制。方法链脲佐菌素诱发大鼠DM后给予胡芦巴多糖A2治疗,观察其对血糖、血脂、肾功能和肾脏病理改变的影响。结果与模型组比较,多糖A2组大鼠血糖明显降低（Ρ〈0.01）;TG、TC、LDL-C水平均明显降低（P〈0.01）,而HDL-C水平则明显升高（P〈0.01）;尿蛋白排泄率（UAlb）、血肌酐（Scr）和尿素氮（BUN）均显著降低（P〈0.01）;光电镜结果表明多糖A2组大鼠肾小球病变明显减轻,免疫组化结果发现多糖A2组大鼠肾脏CTGF蛋白表达明显减少（P〈0.01）。结论DM大鼠给予多糖A2治疗后,可通过降低血糖,调节脂代谢紊乱、改善DM大鼠肾脏功能和结构损伤,多糖A2可能通过下调CTGF蛋白表达抑制ECM增多,从而减轻DN病变。     

Function and regulation of taurine transport at the inner blood-retinal barrier

In the retina, taurine exerts a number of neuroprotective functions as an osmolyte and antioxidant. The purpose of the present study was to elucidate the taurine transport system(s) at the inner blood-retinal barrier (BRB). [(3)H]Taurine transport at the inner BRB was characterized using in vivo integration plot analysis and a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells). The expression of the taurine transporter (TauT) was demonstrated by RT-PCR and immunoblot analyses. The apparent influx permeability clearance of [(3)H]taurine in the rat retina was found to be 259 muL/(ming retina), supporting carrier-mediated influx transport of taurine at the BRB. [(3)H]Taurine uptake by TR-iBRB2 cells was Na(+)-, Cl(-)- and concentration-dependent with a K(m) of 22.2 muM and inhibited by TauT inhibitors, such as beta-alanine and hypotaurine. RT-PCR and immunoblot analyses demonstrated that TauT is expressed in TR-iBRB2 and primary cultured human retinal endothelial cells. The uptake of [(3)H]taurine and the expression of TauT mRNA in TR-iBRB2 cells increased under hypertonic conditions but decreased following pretreatment with excess taurine. In conclusion, TauT most likely mediates taurine transport and regulate taurine transport at the inner BRB.     

Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats

Aims/hypothesis: A strong positive correlation has been found between lipid peroxidation product and vascular endothelial growth factor concentrations in the vitreous of patients with proliferative diabetic retinopathy. To establish a causal relation between diabetes-associated enhanced oxidative stress and vascular endothelial growth factor production, we evaluated two antioxidants, dl-α-lipoic acid and taurine, on retinal vascular endothelial growth factor protein and mRNA expression and on parameters of oxidative stress in streptozotocin-diabetic rats. Methods: Our experiments were on control rats and streptozotocin-diabetic rats with a 6-week duration of diabetes, treated with or without dl-α-lipoic acid (100 mg · kg^–1· d^–1, i. p.) or taurine (1 % in the diet) starting from induction of diabetes. Vascular endothelial growth factor protein in retinal homogenates was assessed by sandwich ELISA with an affinity-purified polyclonal antibody and vascular endothelial growth factor mRNA by ribonuclease protection assay. Retinal lipid peroxidation products i. e. malondialdehyde plus 4-hydroxyalkenals were quantified with n-methyl-2-phenylindole. Retinal reduced and oxidized glutathione, ascorbate, dehydroascorbate, and sorbitol pathway intermediates were measured spectrofluorometrically, and taurine by reverse-phase HPLC. Results: Vascular endothelial growth factor protein concentration (means ± SD) was increased in diabetic rats compared with control rats (33 ± 7 vs 19 ± 5 pg/mg total protein, p < 0.01) This increase was attenuated by taurine (26 ± 8, p < 0.05) and prevented by dl-α-lipoic acid (21 ± 4, p < 0.01). Vascular endothelial growth factor mRNA abundance was reduced by 1.4-fold in diabetic rats compared with control rats and this decrease was attenuated but not completely prevented by both antioxidants. Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats compared with control rats, and both antioxidants arrested accumulation of lipid peroxidation products. Taurine, reduced glutathione, oxidized glutathione, ascorbate, dehydroascorbate and sorbitol pathway intermediate concentrations as well as oxidized glutathione/reduced glutathione and dehydroascorbate/ascorbate ratios were similar in control and diabetic rats treated with or without taurine. Conclusion/interpretation: Oxidative stress is directly involved in up regulation of vascular endothelial growth factor protein in the retina during early diabetes. [Diabetologia (2001) 44: 1102–1110] Received: 29 December 2001 and in revised form: 21 May 2001     

2型糖尿病大鼠心肌组织MMP-2、MMP-9、TIMP-1的表达与胶原代谢的关系

目的 了解2型糖尿病（T2DM）大鼠模型心肌组织基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）及其组织抑制物1（TIMP-1）的mRNA表达变化、蛋白水平及组织定位，探讨MMPs／TIMPs在T2DM心肌病变发生发展中的作用。方法 Masson染色观察心肌胶原含量变化；RT-PCR方法观察心肌MMP-、MMP-9和TIMP-1mRNA表达；免疫组化方法测定MMP-2、MMP-9、TIMP-1的蛋白表达和组织定位。结果 T2DM大鼠心肌胶原纤维明显增多；MMP-2mRNA表达明显下调，蛋白水平下降；MMP-9、TIMP-1的mRNA表达均增加，MMP-9、TIMP-1的蛋白水平也升高，但MMP-9／TIMP-1的比值下降。结论 T2DM大鼠心肌组织胶原聚集，心肌纤维化。MMPs／TIMP-1比例失衡可能与T2DM心肌病变的发生有关。     

Oral taurine supplementation prevents the development of ethanol-induced hypertension in rats.

Taurine is known to lower blood pressure in essential hypertension and some experimental hypertensive models. Taurine has also been reported to activate aldehyde dehydrogenase and to inhibit the elevation of plasma acetaldehyde concentration after ethanol intake. Because acetaldehyde, the first metabolite of ethanol, is suspected to be responsible for many adverse effects of alcohol consumption, we examined the effect of taurine supplementation on ethanol-induced hypertension and abnormalities in the intracellular cation metabolism in Witar-Kyoto rats. In Study 1, systolic blood pressure and intraplatelet free calcium were significantly higher in rats who received 15% ethanol in drinking water than in control rats. Oral taurine supplementation (1% taurine and 15% ethanol in drinking water) completely prevented the development of ethanol-induced hypertension. Intraerythrocyte sodium and intraplatelet free calcium were significantly decreased in taurine-supplemented rats as compared with rats who received 15% ethanol only. In Study 2, hemoglobin-associated acetaldehyde (HbAA) was measured as a marker of protein-bound acetaldehyde. HbAA was significantly elevated in rats who received 5% ethanol in drinking water as compared with control rats. Taurine supplementation (1% taurine and 5% ethanol in drinking water) significantly decreased HbAA. Our findings suggest that the oral supplementation of taurine prevents ethanol-induced hypertension by decreasing protein bound acetaldehyde and altering the cation handling by the membrane.     

Taurine and osmoregulation: platelet taurine content, uptake, and release in type 2 diabetic patients

In this study, plasma and platelet taurine content and fluxes were determined in 38 type 2 diabetic patients and in 26 healthy control subjects. Taurine levels in diabetic patients were significantly lower than in control subjects both in plasma (32.1 v 48.6 micromol/L, P = .000) and platelets (148 v 183 nmol/mg protein, P = .043). Platelet taurine uptake in diabetic patients was significantly reduced (321.2 v 524.9 pmol total taurine 10(8) platelet(-1) min(-20), P = .000), whereas taurine release increased in comparison to healthy controls (38.7 v 29.5% of platelet 3H taurine at the start of incubation, P = .000). These results may reflect modified systems of taurine carriers or a compensatory mechanism in response to an increase of other organic osmolytes.     

牛磺酸通过调控细胞周期蛋白抑制肝星状细胞增殖

目的进一步研究牛磺酸对肝星状细胞(HSC)增殖抑制作用的机制。方法用四甲基偶氮唑盐法检测细胞增殖;流式细胞仪测定细胞周期;免疫细胞化学和实时荧光定量PCR测定细胞周期调控蛋白Cyclin D1和P21waf1表达。结果牛磺酸对HSC增殖具有抑制作用,在浓度为5、10、20,30、40、50 mmol/L 作用48h时的抑制率分别为6.7%、14.4%、23.3%、32.2%、36.7%和45.6%,t值为2.939～6.369,P<0.05～0.01。流式细胞仪检测发现牛磺酸可阻滞HSC由G0/G1期向S期转换,使G0/G1期细胞增多,S期细胞减少。G0/G1期、S期细胞,牛磺酸浓度为40 mmol/L时,分别为(68.2±1.4)%和(26.2±1.3)%,与对照组分别为(56.2±1.7)%和(38.5±0.8)%,差异有统计学意义,t≥5.422,P<0.01。牛磺酸可抑制Cyclin D1表达、促进P21waf1表达,用免疫细胞化学染色结合数码图像分析系统软件分析发现牛磺酸浓度在40 mmol/L时HSC的Cyclin D1表达的平均吸光度为0.13±0.02,P21waf1为0.19±0.02,对照组分别为0.18±0.02和0.14±0.01,差异有统计学意义,t=6.689和t=6.528,P<0.01。实时荧光定量PCR检测也发现经40 mmol/L牛磺酸处理的HSC的Cyclin D1 mRNA表达量(拷贝数与106磷酸甘油醛脱氢酶比值)降低为5776.7±3345.0,对照组为18 400.6±1374.8,而P21waf1 mRNA表达量(拷贝/106磷酸甘油醛脱氢酶)增多为44 866.7±3910.7,对照组为16 933.3±960.9。结论牛磺酸通过抑制Cyclin D1表达、促进P21waf1表达,使HSC阻滞于G0/G1期,而抑制HSC增殖。     

牛磺酸对离体肝星状细胞增殖及凋亡的影响

目的　观察牛磺酸对肝星状细胞增殖及凋亡的影响 ,并探讨其作用的可能机制。方法　用噻唑蓝 (MTT)法检测细胞增殖 ,流式细胞仪检测细胞周期及凋亡 ,丫啶噔活体染色观察细胞凋亡形态 ,免疫细胞化学结合计算机图像分析系统检测c jun、c fos表达。 结果　在 5～ 5 0mmol/L浓度范围内 ,牛磺酸能剂量依赖性地抑制肝星状细胞增殖 ,可使G0 /G1期细胞增多 ,S期细胞减少 ,并能明显抑制c jun、c fos的表达 (P <0 .0 1)。此外 ,牛磺酸尚可抑制血小板源生长因子BB对肝星状细胞的促增殖作用 ,而牛磺酸对肝星状细胞凋亡无诱导作用。结论　牛磺酸可显著抑制肝星状细胞增殖 ,使肝星状细胞阻滞于G0 ～G1期 ;牛磺酸对肝星状细胞增殖的抑制作用与其抑制c jun、c fos的表达有关 ;牛磺酸不能诱导肝星状细胞凋亡。     

罗格列酮对糖尿病大鼠肾脏色素上皮衍生因子、基质金属蛋白酶2及转化生长因子β1表达的影响

45只SD大鼠分为正常对照组、糖尿病对照组、糖尿病罗格列酮治疗组,实验12周末以免疫组织化学和RT-PCR检测肾脏色素上皮衍生因子(PEDF)、基质金属蛋白酶2(MMP-2)和转化生长因子β1(TGF-β1)的表达.结果 显示,罗格列酮治疗可降低糖尿病大鼠增高的肾脏重量/体重比值、肌酐、尿素氮、尿蛋白排泄率、甘油三酯水平(均P＜0.01).罗格列酮增加糖尿病大鼠肾脏降低的PEDF、MMP-2蛋白表达,降低升高的TGF-β1蛋白表达(均P＜0.01).PEDF mRNA的表达也呈相似趋势.提示罗格列酮可通过调节肾脏PEDF、MMP-2及TGF-β1的表达对肾脏起到保护作用.

Abstract：

Forty-five male SD rats were divided into normal group, diabetic control group, and rosiglitazone treatment diabetic group.By the end of 12 weeks, the expressions of pigment epithelium-derived factor(PEDF), matrix metalloproteinase-2 (MMP-2), and transforming growth factor-β1 (TGF-β1) in the kidney were determined by immunohistochemistry and RT-PCR.The results showed that rosiglitazone decreased the increased kidney weight/body weight ratio, serum creatinine, blood ureanitrogen, urinary albumin excretion, triglyceride levels in diabetic rats (all P＜0.01).Rosiglitazone prevented the decreasing of protein expressions of PEDF and MMP-2 and the increasing of protein expression of TGF-β1 (all P＜0.01).PEDF mRNA showed a similar change,suggesting that renoprotection of rosiglitazone on diabetic rats may be mediated through regulating the expressions of PEDF, MMP-2, and TGF-β1.