Regulation of inflammatory response in monocytes by PPARγ agonist

目的 探讨过氧化物酶体增殖物激活受体γ( PPARγ)激动剂对单核细胞炎症反应的影响.方法 体外培养THP-1人单核细胞,将细胞分为对照组、实验组、吡格列酮组和GW9662组.对照组仅加入细胞培养液;实验组用胰腺炎相关性腹水(PAAF)刺激细胞;吡格列酮组在PAAF作用前加入终浓度为20μmol/L的PPARγ激动剂吡格列酮进行干预;GW9662组:在吡格列酮干预前30 min,先行加入PPARγ拮抗剂GW9662,最后加入PAAF.分组处理6h后收集各组细胞,采用Real-Time PCR技术检测促炎症细胞因子肿瘤坏死因子α(TNF-α)和白介素6(IL-6)mRNA的表达;分别采用RT-PCR和Western blotting法检测PPARγ mRNA和蛋白的表达.结果 PAAF刺激后,与对照组比较,实验组、吡格列酮组和GW9662组细胞TNF-α和IL-6 mRNA的相对表达量明显升高,PPARγ mRNA的相对表达量明显降低,差异均有统计学意义(P＜0.05);与实验组比较,吡格列酮组TNF-α和IL-6 mRNA的相对表达量明显降低,PPARγ mRNA的相对表达量明显升高,差异均有统计学意义(P＜0.05);与吡格列酮组比较,GW9662组TNF-α和IL-6 mRNA的相对表达量均明显升高,PPARγ mRNA的相对表达量明显降低,差异也有统计学意义(P＜0.05).Western blotting检测结果显示:各组PPARγ的蛋白表达与mRNA表达的变化趋势相似,但吡格列酮组与对照组、GW9662组与吡格列酮组比较,差异均无统计学意义(P＞0.05).结论 PPARγ激动剂可通过上调PPARγ表达,减少PPAF刺激所致的促炎症细胞因子的产生,从而抑制单核细胞的炎症反应.     

Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells

Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM). Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipidmediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively. Results TGF-β was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β was significantly inhibited by CTGF antisenes. ODNs CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium. Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.     

Tong-xin-luo capsule inhibits left ventricular remodeling in spontaneously hypertensive rats by enhancing PPAR-γ expression and suppressing NF-κB activity

Background Tong-xin-luo capsule （TXL）, used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats （SHR）.
Methods Sixteen eight-week-old SHRs were randomized into an SHR group （n=8） and a TXL group （n=8） that were given Tong-xin-luo capsule （1.5 mg·kg^-1·d^-1）. Eight Wistar Kyoto （WKY） rats fed with 0.9% NaCl served as the control group （WKY group）. Systolic blood pressure （BP）, body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 （NF-κB P65） and peroxisome proliferators activated receptor y （PPAR-γ） protein and phosphorylated inhibitor kappa a （IκBα） protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IκBα and NF-κB were measured by co-immunoprecipitation. PPAR-γ mRNA, collagen Ⅰ mRNA and collagen Ⅲ mHNA were measured by real-time PCR.
Results TXL inhibited NF-κB P65 expression and ventricular remodeling and suppressed the activation of NF-κB compared with the SHR group （P〈0.01, P〈0.05）. TXL reduced IκBα phosphorylation, increased expression of PPAR-γ protein and enhanced the physical interaction of the P65-P50 heterodimer with IκBα. The mRNA expression of PPAR-γ was enhanced but the mRNA expression of collagen Ⅰ mRNA and collagen Ⅲ mRNA were suppressed by TXL. Conclusions In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process     

过氧化物酶增殖物激活受体γ抑制大鼠肝星状细胞中转化生长因子-β1诱导的结缔组织生长因子表达

目的 探讨过氧化物酶增殖物激活受体γ(PPARγ)对大鼠肝星状细胞(HSC)中转化生长因子-β1(TGF-β1)诱导的结缔组织生长因子(CTGF)表达的抑制作用.方法 常规培养大鼠HSC,预先给予或不给予PPARγ特异性拮抗剂GW9662处理,再经系列浓度的PPARγ天然配体(15-d-PGJ2)或合成配体(GW7845)及TGF-β1序贯作用后,通过半定量RT-PCR及Western-blotting分析CTGF表达状况,透射电镜观察HSC形态学变化.结果 15-d-PGJ2和GW7845可显著抑制HSC中TGF-β1诱导的CTGF表达(同时在转录和转录后水平),且PPARγ配体对CTGF表达的抑制作用可被GW9662部分或完全逆转,说明此种抑制效应确由PPARγ所介导;电镜观察亦显示HSC由活化态向静息态的形态学转变.结论 PPARγ活化可显著抑制HSC中TGF-β1诱导的CTGF表达,提示PPARγ可作为逆转肝纤维化治疗的新的有效靶点.

Abstract：

Objective To investigate the effect of peroxisome proliferator-activated receptor gamma(PPARγ)activation on transforming growth factor betal(TGF-β1)-induced connective tissue growth factor(CTGF)expression in rat hepatic stellate cells(HSCs).Methods Cultured HSCs with or without PPARγ-specific antagonist GW9662 treatment prior to the addition of an increasing amount of PPARγ natural ligand(15-d-PGJ2)or synthetic ligand(GW7845)were stimulated with TGF-β1.The mRNA and protein levels of CTGF expression were detected by semi-quantitative RT-PCR and Western blotting,respectively.The morphological changes of the HSC were obgerved by electron microscope.Results 15-d-PGJ2 and GW7845 significantly inhibited TGF-β1-induced CTGF expression at both mRNA and protein levels in HSCs, and the inhibitory effect was dramatically,if not completely,abolished by pretreatment with GW9662,suggesting that the inhibition was mediated by PPARγ. Morphological observation revealed that PPARγactivation caused obvious changes of HSCs from activated to quiescent phenotypes.Conclusion PPARγ ligand shows potent inhibitory effect on TGF-β1-induced CTGF expression in rat HSCs,suggesting its potential as a candidate agent for treatment and prevention of hepatic fibrosis.     

The expression of PPARγ in reflux esophagitis, Barrett esophagus and esophageal adenocarcinoma

目的 观察反流性食管炎、Barrett食管和食管腺癌中食管上皮细胞过氧化物酶体增殖物激活受体γ(PPARγ)的表达及细胞增殖的变化特点.方法 胃镜下取20例反流性食管炎(RE组)、20例Barrett食管(BE组)和6例食管腺癌(EA组)和20例慢性浅表性胃炎(正常对照组)的食管黏膜组织进行活检,免疫组化法和免疫印迹法测定各组黏膜组织食管上皮细胞PPARγ和增殖细胞核抗原(PCNA)的蛋白表达.结果 免疫组化法显示RE、BE、EA组PPARγ的阳性表达率分别为25%、30%、33%,均高于正常对照组的10%(P<0.05);免疫印迹法显示RE、BE、EA组的PPARγ蛋白吸光度比值分别为0.28±0.15、0.21±0.18、0.32±0.13,均高于正常对照组的0.08±0.06(P<0.05);RE、BE、EA组3组间的PPARγ表达差异无统计学意义(P>0.05).免疫组化法显示正常对照组、RE组、BE组、EA组PCNA的阳性表达率分别为25%、60%、75%、100%.结论 从正常食管到反流性食管炎、Barrett食管、食管腺癌,食管上皮的细胞增殖明显增加,伴随着PPARγ蛋白的表达增加,提示PPARγ可能参与了反流性食管炎、Barrett食管、食管腺癌发病过程中细胞增殖的调控.     

Telmisartan but not Valsartan Inhibits TGF-β-mediated Accumulation of Extracelluar Matrix via Activation of PPARγ

Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor γ (PPARγ) has been proposed to decrease the effects of transforming growth factor-β (TGF-β) on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin Ⅱ type 1 receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced glomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARγ were detected by Western blot. Activation of PPARγ response element (PPRE) was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin Ⅱ type 1 receptor blocker, up-regulated PPARγ protein levels in a dose-dependent manner (P<0.05). Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner (P<0.05). Furthermore, telmisartan inhibited TGF-β-induced α-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-γ, blocked the inhibitory effects of telmisartan on TGF-β-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARγ agonist against TGF-β-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease.     

姜黄素对非酒精性脂肪肝家兔血脂及肝组织PPAR-γ 水平的影响

目的:观察姜黄素对非酒精性脂肪肝病(NAFLD)家兔血脂、胰岛素抵抗指数及肝组织过氧化物酶体增殖物激活受体γ(PPAR-γ)水平的影响。方法:34只家兔制备NAFLD模型,随机分为姜黄素组和NAFLD组各17只,均予基础饲料喂养,姜黄素组家兔每天按200mg/kg体质量给予姜黄素混悬液灌胃,NAFLD组给予相同容积的生理盐水,治疗1个月。治疗前后检测血甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FBG)、空腹胰岛素(FNS),并计算胰岛素抵抗(HOMA-IR)指数,免疫组织化学法测定肝组织PPAR-γ蛋白表达,观察肝组织病理学变化。结果:治疗后姜黄素组血浆TG、TC、LDL-C显著降低(P<0.01),HDL-C显著升高(P<0.05),胰岛素抵抗指数显著降低(P<0.05),PPAR-γ蛋白表达显著升高(P<0.05),肝脂肪变性明显好转。结论:姜黄素可降低NAFLD模型家兔血脂、肝脏脂质合成与聚积,对NAFLD有治疗作用。     

PPAR-γ在高血压血管平滑肌细胞表型转化中的作用

目的 观察过氧化物酶体增殖物激活受体-γ(peroxisome proliferator activated reeeptors-γ,PPAR-γ)在高血压血管平滑肌细胞(VSMC)表型转化中的作用.方法 应用基因重组技术使PPAR-γ过表达和表达抑制,Western blot方法 检测分化型VSMC标志物α-SMA和末分化型VSMC标志物OPN的蛋白表达,应用DNA合成率检测和细胞计数的方法 测定细胞增殖率,常规病理切片和HE染色观察血管形态学改变.结果 ①PPAR-γ激动剂罗格列酮可降低SHR大鼠血压,并改善丰动脉血管重构.②SHR大鼠主动脉中OPN表达增多而α-SMA表达减少,应用罗格列酮可抑制上述改变.③SHR大鼠来源的VSMC中OPN表达增多而α-SMA表达减少,细胞增殖率升高,PPAR-γ过表达使细胞增殖率降低,并抑制OPN和α-SMA的表达改变.结论 PPAR-γ可抑制高血压VSMC向未分化表型的转化,可能是其改善高血压血管重构的重要机制.     

过氧化物酶体增殖物激活型受体γ在心肌间质纤维化中的作用及其机制

目的 探讨过氧化物酶体增殖物激活型受体γ(peroxisome proliferator activated receptorγ,PPARγ)不同表达与大鼠心肌间质纤维化之间关系以及其在心肌间质纤维化进程中的作用和机制.方法 雄性SD大鼠48只随机分成4组:(1)对照组(C 组)16只,采用0.05% ISO[5 mg/(kg·d)×10 d]皮下注射制作大鼠心肌纤维化模型;(2)早期干预组(Pa组)12只,造模同时给予PPARγ激动剂罗格列酮 100 mg/(kg·d),腹腔注射56 d;(3)晚期干预组(Pp组)12只,造模10 d后同样应用罗格列酮46 d;(4)空白组(B组)8只.建模后观测各组左心室质量指数、心肌PPARγ mRNA水平、左室心肌组织羟脯氨酸浓度、胶原容积积分(collagen volume fraction,CVF)并检测PPARγ、TGF-β、CTGF、MMP9表达.结果 在观测指标左心室质量指数、CVF、心肌组织羟脯氨酸浓度和PPARγ、TGF-β、CTGF、MMP9表达上,Pa组、Pp组和C组均较B组明显增加(P<0.05),Pa组和Pp组均较C组明显减少(P<0.05),Pa组减少更明显.结论 PPARγ可能在心肌间质纤维化进程中发挥重要作用,可能是促进心肌胶原合成的重要信号分子.PPARγ活化可减少TGF-β、CTGF、MMP9表达和胶原沉积,从而减缓ISO诱导的心肌纤维化,早期干预效果更明显,此作用机制可能通过抑制TGF-β、CTGF的过度表达来实现.     

TSP-1、TGF-β和PPAR-γ在脑胶质瘤中的表达及其与微血管密度的关系

目的探讨凝血酶敏感蛋白-1(TSP-1)、生长转化因子-β(TGF-β)和过氧化物酶体增殖物激活受体-γ(PPAR-γ)在脑胶质瘤中的表达及其与血管生成的关系。方法应用免疫组织化学法对62例胶质瘤组织中的TSP-1、TGF-β和PPAR-γ的表达及微血管密度(MVD)进行检测。结果 TSP-1、TGF-β和PPAR-γ在低级别胶质瘤中的阳性率分别为78.1%、43.7%和93.7%;在高级别胶质瘤中的阳性率分别为46.7%、93.3%和40.0%,PPAR-γ、TSP-1与TGF-β的表达均呈负相关(P<0.05)。低级别组MVD为26±5.2,高级别组MVD为41±7.3,二者之间的差异有统计学意义(P<0.05)。TSP-1、PPAR-γ与MVD呈负相关(P<0.05),TGF-β与MVD呈正相关(P<0.05))。结论 TSP-1、TGF-β、PPAR-γ与脑胶质瘤组织的MVD密切相关,可能参与了脑胶质瘤血管生成的调控。     

大鼠肾脏损伤早期HIF-1α、PPAR-γ的表达及其对肾脏的保护机制

目的探讨经体表创伤后肾脏组织中缺氧诱导因子-1α(HIF-1α)、过氧化物酶体增殖物激活受体γ(PPAR-γ)表达的变化,及创伤后肾脏损伤与修复的作用机制。方法采用自由落体生物撞击仪撞击大鼠脊肋区复制创伤动物模型。实验大鼠分为5组,包括非创伤对照组,创伤后1、6、12、24 h组。采用免疫组织化学方法进行HIF-1α、PPAR-γ染色。结果肾脏创伤后1、24 h HIF-1α表达增强,分布于皮质远曲小管、肾盏旁小管、髓质小管;6、12 h表达减弱,局限于肾盏旁小管、髓质外带小管。各组间比较差异有统计学意义(P<0.05)。PPAR-γ1、24 h呈阳性表达,分布于髓质小管上皮细胞;6、12 h呈阴性表达,各组间比较差异有统计学意义(P<0.05)。结论 HIF-1α、PPAR-γ可能参与了肾脏创伤后缺血、缺氧、再生、修复的过程。     

过氧化物酶体增殖物激活型受体γ在心肌间质纤维化中的作用及机制研究

目的 研究过氧化物酶体增殖物激活型受体γ（peroxisome proliferator activated receptorγ,PPARγ）不同表达对与大鼠心肌间质纤维化之间的关系,探讨过氧化物酶体增殖物激活型受体γ心肌间质纤维化进程中的作用和机制。方法 雄性SD大鼠48只随机分成4组：① 对照组（C 组）16只,采用0.05 %ISO（5 mg•kg-1•d-1×10 d）皮下注射制作大鼠心肌纤维化模型;②早期干预组（Pa组）12只,造模同时给予PPARγ激动剂罗格列酮 100 mg•kg-1•d-1,腹腔注射56 d;③ 晚期干预组（Pp组）12只,造模10 d后给予PPARγ激动剂罗格列酮 100 mg•kg-1•d-1,腹腔注射46 d;④空白组（B组）12只。建模成功后计算各组左心室质量指数,RT-PCR检测心肌PPARγ mRNA水平;比色法检测左室心肌组织中羟脯氨酸浓度;进行VG染色,测算胶原容积积分（collagen volume fraction,CVF）;免疫组化染色半定量检测PPARγ、TGF-β、CTGF、MMP9表达。结果 Pa组、Pp组和C组的左心室质量指数、CVF、心肌组织羟脯氨酸浓度和PPARγ、TGF-β、CTGF、MMP9表达均较B组明显增加（P<0.05）;Pa组和Pp组的左心室质量指数、CVF、心肌组织羟脯氨酸浓度和PPARγ、TGF-β、CTGF、MMP9均较C组明显减少（P<0.05）,Pa组减少更明显。结论 过氧化物酶体增殖物激活型受体γ可能在心肌间质纤维化进程中发挥重要作用,它可能是促进心肌胶原合成的重要信号分子。PPARγ活化可减少TGF-β、CTGF、MMP9表达,减少胶原沉积,从而减轻和延缓ISO诱导的心肌纤维化,早期干预效果更明显,这种作用机制可能是通过抑制TGF-β和CTGF的过度表达来实现。     

罗格列酮拮抗博莱霉素致大鼠肺纤维化的实验研究

目的探讨罗格列酮抑制肺纤维化的作用及其机制。方法将24只大鼠分为生理盐水对照组、罗格列酮对照组、博莱霉素组、罗格列酮干预组,予博莱霉素诱导大鼠肺纤维化。HE染色和Masson染色行病理学检查;试剂盒检测肺组织中羟脯氨酸含量;应用Westen blot及荧光定量实时逆转录聚合酶链反应(RT-PCR)检测过氧化物酶体增殖物激活受体γ(PPARγ)、基质金属蛋白酶9(MMP-9)和转化生长因子β1(TGF-β1)的表达;采用酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液(BALF)中TGF-β1浓度。结果博莱霉素气管内注入后,Ashcroft评分,肺组织胶原沉积、羟脯氨酸含量,BALF中TGF-β1水平及肺组织中TGF-β1、PPARγ、MMP-9表达较生理盐水对照组增加;给予罗格列酮干预后,除PPARγ表达进一步增加外,上述指标均下降。博莱霉素组PPARγ蛋白表达水平与TGF-β1mRNA、MMP-9mRNA表达水平分别呈负相关。结论罗格列酮对博莱霉素诱导的肺纤维化进程有拮抗作用,其具体机制可能与上调PPARγ蛋白表达,抑制TGFβ1、MMP-9mRNA转录有关。     

妊娠期糖尿病孕妇腹直肌及腹部皮下脂肪中PPARβ表达量的检测及其与糖脂代谢的关系

目的:研究妊娠期糖尿病(GDM)孕妇腹直肌及腹部皮下脂肪中过氧化物酶体增殖物激活受体β(PPARβ)表达量与糖脂代谢的关系。方法:对2012年5月~2016年3月在我院产科进行常规产检且拟行择期剖宫产的孕妇进行回顾性分析,筛选74例健康孕妇及58例GDM孕妇,分别纳入对照组和妊娠期糖尿病组(GDM组)。剖宫产术中采集腹直肌及腹部皮下脂肪,测定PPARβ的表达量;孕中晚期采集外周血并测定血糖代谢、血脂代谢指标及脂肪细胞因子含量。结果:GDM组孕妇腹直肌及腹部皮下脂肪中PPARβ的mRNA表达量及蛋白表达量均显著低于对照组;GDM组孕妇的稳态模式胰岛素分泌指数(HOMA-β)、稳态模式胰岛素抵抗指数(HOMA-IR)、OGTT血糖曲线下面积(AUCG)及血清中低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、胆固醇(TC)、瘦素(Leptin)、抵抗素(Resistin)、趋化素(Chemerin)含量显著高于对照组,早期胰岛素分泌指数(ΔI_(30)/ΔG_(30))、胰岛素混合敏感指数(ISIcomp)水平及血清中高密度脂蛋白胆固醇(HDL-C)、Omentin-1、脂联素(adiponectin,ADPN)含量显著低于对照组;PPARβ的mRNA表达量及蛋白表达量与HOMA-β、HOMA-IR、AUCG、LDL-C、TG、TC、Leptin、Resistin、Chemerin呈负相关,与ΔI_(30)/ΔG_(30)、ISIcomp、HDL-C、Omentin-1、ADPN呈正相关。结论:GDM孕妇腹直肌及腹部皮下脂肪中PPARβ的表达量显著下调且与GDM孕妇体内糖脂代谢异常密切相关。     

Tenascin-x facilitates myocardial fibrosis and cardiac remodeling through transforming growth factor-β1 and peroxisome proliferator- activated receptor γ in alcoholic cardiomyopathy

Background  Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-β1 and peroxisome proliferator-activated receptor γ (TGFβ₁-PPARγ) pathway in alcoholic cardiomyopathy (ACM).

Methods  Experimental animals were divided into control (group A) and tenascin-x knock-out groups (group B) receiving alcohol. Six months post treatment, cardiac ejections fraction (EF), fractional shortening (FS), left ventricle end-diastole internal diameter (LVEDd) and collagen column fraction (CVF) were observed. Tenascin-x, smad-3, TGFβ₁, smad-7 and PPARγ protein expression levels were detected by Western blotting.

Results  Six months post treatment, EF and FS values were higher in group B than in group A (P <0.05 and P <0.01, respectively), while LVEDd and CVF were lower in group B (P <0.05 and P <0.01, respectively). Tenascin-x, smad-3 and TGFβ₁ protein expression levels were higher in group A, while smad-7 and PPARγ levels were lower than in group B (P <0.01), as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ₁ (P <0.001).

Conclusion  Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ₁ and downregulation of PPARγ.

     

益气养阴与解毒活血中药对心肌梗死后大鼠早期心室重构心肌NF-κB和PPAR-γ mRNA表达的影响

目的 研究益气养阴活血与解毒活血中药对心肌梗死后大鼠早期心室重构的影响及作用机制.方法 结扎Wistar雄性大鼠冠状动脉左前降支,造成急性心肌梗死(AMI)模型,随机分为假手术组(只穿刺,不结扎)、模型组、培哚普利组、益气养阴活血组、解毒活血组(每组10只),分别灌胃,另设正常组10只给予等量水.4周后麻醉处死大鼠,检测左室重量指数(LVMI),测定动物血清高敏C-反应蛋白(hs-CRP)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)等炎症因子含量,利用反转录聚合酶链式扩增(RT-PCR)方法检测大鼠缺血心肌核因子κB(NF-κB) mRNA和过氧化物酶增殖体激活受体-γ(PPAR-γ) mRNA的表达水平.结果 与模型组比较,培哚普利组、益气养阴活血组、解毒活血组大鼠的左心室重量和LVMI均不同程度降低(P<0.01,P<0.05).解毒活血组能明显降低血清IL-6(P<0.05);益气养阴活血组和解毒活血组均能使心肌组织的PPAR-γ和NF-κBp65 mRNA的表达明显降低(P<0.05),解毒活血中药对PPAR-γ mRNA降低作用大于益气养阴活血中药(P<0.05).结论 益气养阴活血与解毒活血中药组分通过不同途径减轻大鼠AMI后组织炎症基因的表达,从而抑制大鼠AMI后的心室重构.