分别于兔耳薄、厚皮肤处制备的增生性瘢痕增生程度对比观察

目的 对比观察分别于兔耳薄、厚皮肤处制备的增生性瘢痕增生程度。方法 将8只兔子分为模型组和空白组各4只，模型组每耳选定4个位点，分别为2处薄皮肤的位点（皮肤厚度<1 mm）和2处厚皮肤的位点（皮肤厚度>1.3 mm），每个位点中心至少间隔2 cm，厚皮肤和薄皮肤各做16个位点，在选定位点钻出环形伤口制备HS模型；空白组不作任何处理，正常喂食。观察术后不同时点兔耳创面变化，另观察不同厚度兔耳HE染色、Masson染色，计算兔耳瘢痕增生指数（HI）、成纤维细胞数目（NA）、胶原纤维面积密度（AA）。结果 模型组术后第7～42天，随着时间变化，薄皮肤处和厚皮肤处手术后均形成HS，但厚皮肤处更为明显；空白组厚皮肤处和薄皮肤处正常皮肤在观察期内无明显变化。空白组正常皮肤厚处与薄处HE染色无明显差异；模型组HE染色显示薄处与厚处造模的瘢痕均较对应部位正常皮肤显著升高，其中厚处造模的瘢痕显著高于薄处造模的瘢痕。与空白组薄处皮肤比较，模型组薄处皮肤的表皮和真皮明显增厚，真皮中的微血管和成纤维细胞含量增多，未见瘢痕真皮中的毛囊、汗腺等皮肤附属器，NA明显高于空白组薄处皮肤；与空白组厚处皮肤比...     

丝裂霉素C对瘢痕疙瘩成纤维细胞增殖与Smad2/3蛋白表达的影响

目的研究丝裂霉素C(MMC)对增生性瘢痕成纤维细胞增殖及Smad2/3蛋白的影响。方法用组织块法培养人瘢痕成纤维细胞,采用四唑盐比色(MTT)方法,观察不同浓度MMC对体外培养的瘢痕疙瘩成纤维细胞增殖活性的影响,采用Western印迹技术检测MMC作用下体外培养瘢痕疙瘩成纤维细胞中Smad2/3蛋白的表达。结果不同浓度的MMC对体外培养的病理性瘢痕成纤维细胞活性的抑制呈时间和剂量依赖性。12.5μg/ml MMC开始对瘢痕疙瘩成纤维细胞中Smad2/3蛋白的表达具有明显减弱效应(P<0.05)。结论 MMC一方面通过抑制瘢痕疙瘩成纤维细胞增殖,另一方面通过抑制Smad2/3蛋白的表达而发挥抑制瘢痕增生作用。     

病理性瘢痕组织中SPARC的表达变化及意义

目的观察富含半胱氨酸的酸性分泌糖蛋白（SPARC）在瘢痕疙瘩和增生性瘢痕中的表达变化及其意义。方法病理性瘢痕患者52例,其中瘢痕疙瘩（瘢痕组）和增生性瘢痕组织（增生组）各26例,另取正常皮肤组织5例为对照（对照组）。采用免疫组化SP法检测三组SPARC。将三组组织中的成纤维细胞传代培养（4～6代）,采用Western blot法检测其SPARC。结果瘢痕组、增生组中SPARC表达较弱,虽比对照组高,但P〉0．05;在早期增生性瘢痕（3—6个月）中的表达与晚期（9～12个月）近似（P〉0．05）。瘢痕组、增生组成纤维细胞中SPARC表达均高于对照组（P均〈0．05）。结论病理性瘢痕组织中的SPARC均呈低表达,其成纤维细胞中的SPARC呈高表达,这可能与病理性瘢痕的发生有关。     

SPARC对增生性瘢痕成纤维细胞Ⅰ型胶原蛋白mRNA表达的影响

目的观察富含半胱氨酸的酸性分泌糖蛋白（SPARC）对增生性瘢痕成纤维细胞Ⅰ型胶原蛋白表达的影响。方法用不同浓度重组人SPARC作用于体外培养的增生性瘢痕成纤维细胞（实验组）,并与空白组作对照。用实时荧光定量RT-PCR法检测其Ⅰ型胶原蛋白mRNA表达情况。结果与空白对照组相比,实验组Ⅰ型胶原蛋白mRNA表达明显增高（P〈0．05）。结论SPARC能显著促进增生性瘢痕成纤维细胞Ⅰ型胶原蛋白基因的表达。     

人真皮间充质干细胞防治中老年增生性瘢痕形成早期成纤维细胞的效果

目的探讨人真皮间充质干细胞(hDMSCS)对中老年增生性瘢痕形成早期成纤维细胞的防治机制。方法中老年增生性瘢痕患者12例,按瘢痕形成时间分为6个月组、1年组、2年组,每组各4例,术中留取瘢痕组织标本,分离瘢痕成纤维细胞。采用非接触Transwell共培养体系培养hDMSCS和瘢痕成纤维细胞21 d,瘢痕成纤维细胞用普通6孔板培养相同时间为对照,RT-PCR和Western印迹检测纤维化相关因子α-血管平滑肌肌动蛋白(SMA)、核心蛋白多糖(DCN)mRNA和蛋白表达情况。结果 hDMSCS经诱导成功向成脂、成软骨、成骨细胞分化,符合间充质干细胞最低鉴定标准。共培养21 d后,6个月组、1年组、2年组瘢痕成纤维细胞α-SMA、DCN mRNA及蛋白表达量与对照组比较差异均有统计学意义(P<0.05),其中以增生性瘢痕形成早期(6个月组)α-SMA、DCN mRNA和蛋白变化最为明显。结论 hDMSCS可下调瘢痕成纤维细胞α-SMA mRNA和蛋白的表达,上调DCN mRNA和蛋白的表达,且对早期成纤维细胞作用明显。     

人参皂苷-Rg3对兔耳增生性瘢痕中Bcl-2、Bax表达的影响

目的 研究人参皂苷Rg3(GS-Rg3)对兔耳增生性瘢痕中Bcl-2、Bax的影响.方法建立兔耳增生性瘢痕模型,分成四组.于四组动物耳部增生性瘢痕组织处行局部封闭注射,实验组注射GS-Rg3(浓度6mg/2 ml),对照组注射等体积的0.9％生理盐水,每3 d一次.分别于用药后2w、4w、6 w切取瘢痕组织,经免疫组化法检测Bcl-2及Bax的水平.结果①实验组在用药后2 w Bcl-2表达量逐渐下降,6 w明显减少;而对照组有较多量的Bcl-2表达.②实验组用药后2 wBax表达量明显增加,而对照组则有少量表达.结论GS-Rg3可明显降低Bcl-2蛋白质的表达,增加Bax的表达.     

人参皂苷Rg3对兔耳增生性瘢痕中Caspase-3、细胞色素C表达的影响

目的 研究人参皂苷Rg3(GS-Rg3)对兔耳增生性瘢痕中Caspase-3、细胞色素C的影响.方法 建立兔耳增生性瘢痕模型,并分成四组.于四组动物耳部增生性瘢痕组织处行局部封闭注射,实验组注射GS-Rg3(浓度6 mg/2 ml),对照组注射等体积的0.9%生理盐水,三天一次.分别于用药后2 w、4 w、6 w切取瘢痕组织,经免疫组化法检测Caspase-3、细胞色素C的变化.结果 ①实验组与对照组相比Caspase-3的表达在用药后6 w增加至2.4倍.②实验组与对照组相比细胞色素C的表达在用药后6 w增加至2.8倍.结论 GS-Rg3可明显增加Caspase-3、细胞色素C的表达.     

水蛭素对增生性瘢痕基质金属蛋白酶-2、9表达作用的影响

目的 研究水蛭素对增生性瘢痕组织基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的影响,探讨水蛭素对增生性瘢痕作用机理.方法 取烧伤后6个月内的皮肤增生性瘢痕,体外培养成纤维细胞,ELISA法测定水蛭素作用后MMP-2、MMP-9表达含量.结果 水蛭素作用后增生性瘢痕组织内MMP-2、MMP-9含量增加,分别以0.5 U/mL和1 U/mL组作用最明显,与对照组比较差异均有统计学意义(P＜0.01).结论 水蛭素能促进MMP-2、MMP-9表达,有抑制增生性瘢痕的作用.     

miRNAs对人皮肤成纤维细胞光老化的作用及其相关机制

目的探讨miR-146a在紫外线诱导人皮肤成纤维细胞光老化中的作用。方法 10 J/cm~2UVA连续照射成纤维细胞2 w建立光老化模型,分别于首日、3、7、14 d提取总RNA,实时定量PCR检测miR-146a表达量;慢性病毒转染上调miR-146a表达(miR-146a过表达组),荧光显微镜观察转染效率,并验证细胞内miR-146a表达量;未经处理的成纤维细胞作为空白对照组;UVA+miR-146a组为miR-146a过表达后再用UVA照射。MTT法检测四组细胞增殖情况;实时定量PCR检测四组细胞内老化相关基因mRNA表达情况;Western印迹法检测四组细胞中Smad4蛋白表达情况。结果 UVA照射第3、7、14天UVA照射组miR-146a表达量持续降低,且明显低于同期空白对照组(P<0.05)。慢性病毒载体转染后,miR-146a过表达组第7、14天miR-146a表达量明显高于同期空白对照组(P<0.05)。UVA照射组、UVA+miR-146a组A值明显低于空白对照组、miR-146a过表达组(P<0.01);miR-146a过表达组A值与空白对照组之间无统计学差异(P>0.05);UVA+miR-146a组A值明显高于UVA照射组(P<0.01)。UVA照射组、UVA+miR-146a组p53、p21、p16 mRNA表达量均明显高于空白对照组、miR-146a过表达组(P<0.01);miR-146a过表达组p53、p21、p16mRNA表达量与空白对照组之间无统计学差异(P>0.05);UVA+miR-146a组p53、p21、p16 mRNA表达量明显低于UVA照射组(P<0.01)。UVA照射组、UVA+miR-146a组细胞内Smad4蛋白表达量明显高于空白对照组、miR-146a过表达组(P<0.01);miR-146a过表达组与空白对照组Smad4蛋白表达量之间无统计学意义(P>0.05);UVA+miR-146a组Smad4蛋白表达量明显低于UVA照射组(P<0.01)。结论 UVA诱导光老化人皮肤成纤维细胞中miR-146a表达被抑制,上调其表达可抑制Smad4表达,促进光老化细胞增殖,起到抗老化作用。     

皮肤病理性瘢痕及瘢痕癌组织中Smad mRNA和蛋白检测及基因突变

目的分析皮肤病理性瘢痕及瘢痕癌组织中Smad蛋白和基因的表达变化及其基因的突变情况。方法将20份病理性瘢痕组织标本设为观察A组、20份瘢痕癌组织标本设为观察B组,20份正常皮肤组织设为对照组,分别使用免疫组织化学染色和实时荧光PCR(Real time PCR)观察三组标本Smad蛋白和基因的变化情况,同时应用基因测序技术扩增观察A组和观察B组标本的DNA序列,观察Smad基因的突变情况。结果(1)观察B组Smad蛋白和基因的表达水平高于观察A组和对照组(P<0.05),观察A组和对照组之间Smad蛋白和基因的表达水平无统计学差异(P>0.05)。(2)两组观察组标本经过PCR基因扩增后呈现6条目的条带,其中病理性瘢痕及瘢痕癌各3例,致病性与非致病性突变位点未在测序时发现。结论 Smad表达升高可能与瘢痕癌相关,下调Smads基因表达和抑制Smad蛋白活性将可能成为治疗瘢痕癌的药物靶方向。     

Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing

We have previously shown that non-myocytes present in healed 8-week infarct scar overexpress transduction proteins required for initiating the elevated deposition of structural matrix proteins in this tissue. Other work suggests that TGF-beta 1 may be involved in cardiac fibrosis and myocyte hypertrophy. However, the significance of the altered TGF-beta signaling in heart failure in the chronic phase of post-myocardial infarction (MI), particularly in the ongoing remodeling of the infarct scar, remains unexplored. Patterns of cardiac TGF beta 1 and Smad 2, 3, and 4 protein expression were investigated 8 weeks after MI and were compared to relative collagen deposition in border tissues (containing remnent myocytes) and the infarct scar (non-myocytes). Both TGF-beta 1 mRNA abundance and protein levels were significantly increased in the infarct scar v control values, and this trend was positively correlated to increased collagen type I expression. Cardiac Smad 2, 3, and 4 proteins were significantly increased in border and scar tissues v control values. Immunofluorescent studies indicated that Smad proteins localized proximal to the cellular nuclei present in the infarct scar. Decorin mRNA abundance was elevated in border and infarct scar, and the pattern of decorin immunostaining was markedly altered in remote remnant heart and scar v staining patterns of control sections. Expression of T beta RI (53 kDa) protein was significantly reduced in the scar, while the 75 kDa and 110 kDa isoforms of T beta RII were unchanged and significantly increased in scar, respectively. These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.     

Budesonide up-regulates vitamin D receptor expression in human bronchial fibroblasts and enhances the inhibitory effect of calcitriol on airway remodeling

Introduction and objectivesTransforming growth factor β1 (TGFβ1) and dysregulated microRNA-21 (miR-21) expression is associated with TGFβ/Smad signaling pathway activation and fibrosis. While calcitriol has been shown to improve airway remodeling in asthmatic mice, its mechanism remains unknown. In this study, the effect of calcitriol on the TGFβ/Smad signaling pathway and miR-21 expression in human bronchial fibroblasts was investigated to explore the mechanism of action of calcitriol and the inhaled glucocorticoid, budesonide, in airway remodeling.Materials and methodsHuman bronchial fibroblasts were pretreated with budesonide, calcitriol, or budesonide plus calcitriol, and stimulated with TGFβ1 for 48 h. Quantitative real-time PCR was used to determine the expression of miR-21. Western blot was used to determine airway remodeling-related proteins, TGFβ/Smad signaling pathway-related proteins, glucocorticoid receptor, and vitamin D receptor (VDR) expression.ResultsBoth budesonide and calcitriol down-regulated miR-21 expression in human bronchial fibroblasts, up-regulated Smad7 expression, and inhibited the expression of airway remodeling-related proteins. Both budesonide and calcitriol up-regulated the low expression of VDR induced by TGFβ1 in human bronchial fibroblasts. The expression of VDR in the combined treatment group (budesonide plus calcitriol) was significantly higher than that in the calcitriol treatment group. The expression of collagen type I in the combined treatment group was significantly lower than that in the calcitriol treatment group.ConclusionsCalcitriol can up-regulate the expression of VDR in human bronchial fibroblasts and exert an anti-airway remodeling effect. Budesonide can up-regulate the expression of VDR in human bronchial fibroblasts and enhance the inhibitory effect of calcitriol on airway remodeling.     

Rapid atrial pacing induces myocardial fibrosis by down-regulating Smad7 via microRNA-21 in rabbit

Tachycardia-induced atrial fibrosis is a hallmark of the structural remodeling of atrial fibrillation (AF). The mechanisms underlying tachycardia-induced atrial fibrosis remain unclear. In our previous study, we found that Smad7-downregulation promoted the development of atrial fibrosis in AF. Fibroblasts are enriched in microRNA-21 (miR-21), which contributes to the development of fibrosis and heart failure in the cardiovascular system. Our study was designed to test the hypothesis that miR-21 reinforces the TGF-β₁/Smad signaling pathway in AF-induced atrial fibrosis by down-regulating Smad7. Rapid atrial pacing (RAP, 1000 ppm) was applied to the left atrium of the rabbit heart to induce atrial fibrillation and fibrosis. qRT-PCR and northern blot analysis revealed that RAP caused a marked increase in the expression of miR-21. Transfection with a miR-21 inhibitor significantly increased the expression of Smad7, while the expression of collagen I/III significantly decreased. These changes were implicated in the AF-induced release of miR-21 and down-regulation of Smad7. Adult rat cardiac fibroblasts treated with TGF-β₁ showed increased miR-21 expression and decreased Smad7 expression. Pretreatment with a TGF-β₁ inhibitor reduced the TGF-β₁-induced up-regulation of miR-21. Pretreatment with pre-miR-21 and a miR-21 inhibitor significantly decreased and increased Smad7 expression, respectively. This result was negatively correlated with the expression of collagen I/III in fibroblasts. Moreover, the results of a luciferase activity assay suggest that Smad7 is a validated miR-21 target in CFs. Our results provide compelling evidence that the miR-21 specific degradation of Smad7 may decrease the inhibitory feedback regulation of TGF-β1/Smad signaling and serves as a new insight of the mechanism of atrial fibrosis in atrial fibrillation.     

安体舒通对心衰大鼠心肌组织TGF-β/Smads信号通路相关分子表达的影响

目的 观察醛固酮受体阻滞剂安体舒通对心肌梗死后心力衰竭（心衰）大鼠心肌组织中TGF-β/Smads 信号通路相关分子表达的影响,并探讨其意义.方法 健康雄性SD大鼠32只,分为心衰对照组和安体舒通组各11只,假手术组10只,通过结扎冠状动脉构建心肌梗死后心衰模型,假手术组不结扎冠脉.术后2周,假手术组和心衰对照组采用生理盐水、安体舒通组采用安体舒通20 mg/kg灌胃8周.分别于术后2周（灌胃前）、灌胃后8周采用超声心电图监测大鼠左室收缩末期容积（LVESD）、左室舒张末期容积（LVEDD）、左室射血分数（LVEF）和短轴缩短率（FS）.其后处死大鼠并取心脏组织,采用Masson染色测定心肌胶原容积分数（CVF）.采用Real-timePCR法检测三组心肌组织中的TGF-β1、Smad2、Smad3、Smad7 mRNA,Western blot法检测TGF-β1、Smad2、Smad3、Smad7蛋白及胶原纤维Ⅲ蛋白.结果 灌胃前安体舒通组、心衰对照组LVEDD、LVESD较假手术组增加,而EF及FS下降（P均＜0.05）.灌胃后8周,安体舒通组EF、FS高于心衰对照组（P均＜0.05）.心肌CVF心衰对照组＞安体舒通组＞假手术组（P均＜0.05）.大鼠心肌组织中TGF-β1、Smad2、Smad3及Smad7mRNA及其蛋白和胶原纤维Ⅲ蛋白的表达心衰对照组＞安体舒通组＞假手术组（P均＜0.05）.结论 安体舒通可抑制心肌梗死后心衰大鼠TGF-β/Smads信号通路相关分子的表达,改善心肌纤维化.     

依那普利和厄贝沙坦对肾血管性高血压大鼠颈动脉重构及转化生长因子β1/Smads表达的影响

目的观察依那普利和厄贝沙坦单用及联用对肾血管性高血压大鼠(RHR)颈动脉重构及转化生长因子β1(TGF-β1)/Smads表达的影响。方法 8～12周龄雄性Sprague-Dawley(SD)大鼠30只。建立"两肾一夹"RHR模型,设立模型组、假手术组、依那普利组[10mg/(kg·d)]、厄贝沙坦组[50mg/(kg·d)]、联合用药组[厄贝沙坦25mg/(kg·d)+依那普利5mg/(kg·d)],每组6只大鼠。药物连续干预6周。采用HE染色、Masson染色法及免疫组化染色检测颈动脉中膜形态及结构变化并测量中膜厚度、中膜厚度/腔径以及颈动脉中膜α肌动蛋白(α-actin)、增殖细胞核抗原(PCNA)、TGF-β1、磷酸化Smad2/3(p-Smad2/3)、Smad7的表达水平。结果 RHR模型组颈动脉中膜明显肥厚,平滑肌细胞体积增大,排列紊乱;中膜厚度、中膜厚度/腔径、颈动脉中膜平滑肌细胞的增殖指数及胶原纤维面积百分比均高于假手术组[中膜厚度(91.28±11.17)比(52.15±7.18)μm,中膜厚度/腔径(20.75±3.07)%比(9.94±1.52)%,增殖指数(35.31±12.97)%比(1.84±0.52)%,胶原纤维面积百分比(67.53±7.68)%比(15.35±4.47)%,均P<0.01];TGF-β1和p-Smad2/3的表达较假手术组均增多(均P<0.05),Smad7表达较假手术组减少(P<0.01)。依那普利和厄贝沙坦均能改善颈动脉平滑肌肥大和胶原沉积,减小RHR颈动脉中膜厚度、中膜厚度/腔径、平滑肌细胞的增殖指数、胶原纤维面积百分比及TGF-β1和p-Smad2/3的表达(P<0.05),增加Smad7表达(P<0.01),且两药联用较单用更能改善颈动脉重构,降低TGF-β1和p-Smad2/3的表达(P<0.05),增加Smad7表达(P<0.05)。结论依那普利和厄贝沙坦通过影响TGF-β1/Smads信号通路中TGF-β1、p-Smad2/3和Smad7的表达而改善RHR颈动脉重构,且两药联用有协同作用。     

Role of TGF-β1/Smads pathway in carotid artery remodeling in renovascular hypertensive rats and prevention by Enalapril and Amlodipine

Objective To investigate the role of transforming growth factor-β1 (TGF-β1), Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat (RHR) models with “two-kidney and one-clip” were established, including model group (n = 6), sham-operated group (n = 6), Enalapril group (10 mg/kg per day, n = 6), Amlodipine group (5 mg/kg per day, n = 6) and combination group (Amlodipine 2.5 mg/kg per day + Enalapril 5mg/kg per day, n = 6). The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness (MT), MT and lumen diameter ratio (MT/LD), and the expression levels of media α-smooth muscle actin (α-actin), proliferating cell nuclear antigen (PCNA), TGF-β1, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group (P < 0.01). Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 (P < 0.05) and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 (P < 0.05), increased Smad7 expression (P < 0.05). Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group (P < 0.05), but not single Enalapril group. Conclusions TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling in RHR; the role of Amlodipine and Enalapril in inversing carotid artery remodeling may be related to the change of TGF-β1/Smads pathway, the combination treatment of Amlodipine and Enalapril had better effects than single administration of Amlodipine.     

IFN-γ对日本血吸虫病肝纤维化小鼠Smads表达的影响

目的 从转录水平探讨参与TGF-β1信号转导的Smads在日本血吸虫感染的BALB/c小鼠形成肝纤维化过程中,以及IFN-γ治疗后的表达情况. 方法 BALB/c小鼠感染日本血吸虫尾蚴后第16周,将其随机分成3组:安慰剂组、吡喹酮治疗组和吡喹酮联合IFN-γ治疗组,治疗8周.分别在感染后第8周、12周、16周和24周,处死小鼠取肝脏组织,一部分进行天狼猩红染色,观察胶原沉积情况;另一部分提取总mRNA,通过RT-PCR检测Smad2.Smad3,Smad4和Smad7 mRNA的表达水平. 结果 肝纤维化模型在感染16周后形成.胶原表达随着感染时间的延长而增加.胶原表达在吡喹酮联合IFN-γ治疗组表达下降,而在安慰剂组和吡喹酮治疗组之间的差别无统计学意义.在肝纤维化形成过程中,Smad3 mRNA在感染16周时增加到正常水平的2倍;Smad2 mRNA的表达水平在感染12周时下降,在16周时,又恢复到正常水平;Smad4和Smad7 mRNA水平变化不明显.在联合治疗后,Smad7 mRNA水平明显增高,Smad2 mRNA保持在低水平上,Smad3 mRNA高于正常对照组,Smad4 mRNA水平仍无明显变化. 结论 Smad3 mRNA表达上调,Smad2 mRNA表达下调以及Smad7 mRNA的低水平表达可能导致小鼠肝纤维化的形成,IFN-γ可能通过诱导Smad7 mRNA表达上调,从而达到抗纤维化的作用.