Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells

BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.

Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

AIM: To investigate the expression of the transforming growth factor beta 1(TGF-beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n =22), alcoholic steatosis (n =30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood mononuclear cells (PBMC) as samples the gene expression of TGF-beta 1 was examined quantitatively by reverse transcription polymerase chain reaction (RT-PCR) and dot blot. There are 34 healthy subjects served as control. RESULTS: The expression of TGF-beta 1 from all ALD patients was significantly greater than that in controls (1.320 +/- 1.162 vs 0.808 +/- 0.276, P【0.001). The differences of the expressions were significant between the patients from each groups (alcoholic steatosis, alcoholic hepatitis and alcoholic cirrhosis) and the controls (1.168 +/- 0.852, 1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.808 +/- 0.276, P【0.050). No significant differences of TGF -beta 1 mRNA expression were observed between alcohol abusers without liver impairment and controls. The expressions in patients with alcoholic hepatitis and alcoholic cirrhosis were significantly greater than that in alcohol abusers respectively (1.462 +/- 1.657, 1.329 +/- 0.610 vs 0.841 +/- 0.706, P【0.050). No significant differences of TGF-beta 1 mRNA expression were observed between alcoholic fatty liver men and alcohol abusers. CONCLUSION: TGF-beta 1 expression level can be a risk factor for alcoholic liver disease and might be related to the inflammatory activity and fibrosis of the liver in patients.

Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling

Transforming growth factor-beta （TGF-β） type II receptor （TβRⅡ） levels are extremely low in the brain tissue of patients with Alzheimer＇s disease. This receptor inhibits TGF-β1/SMAD signaling and thereby aggravates amyolid-beta deposition and neuronal injury. Dab2, a specific adapter protein, protects T RII from degradation and ensures the effective conduction of TGF-β 1/SMAD signaling. In this study, we used an adenoviral vector to overexpress the Dab2 gene in the mouse hippocampus and investigated the regulatory effect of Dab2 protein on TGF-β1/SMAD signaling in a mouse model of Alzheimer＇s disease, and the potential neuroprotective effect. The results showed that the TβRⅡ level was lower.in APP/PS1 mouse hippocampus than in normal mouse hippocampus. After Dab2 expression, hippocampal TβRⅡ and p-SMAD2/3 levels were signifi- cantly increased, while amyloid-beta deposition, microglia activation, tumor necrosis factor- and interleulin-6 levels and neuronal loss were significantly attenuated in APP/PS1 mouse brain tissue. These results suggest that Dab2 can exhibit neuroprotective effects in Alzheimer＇s disease by regulating TGF-β1/SMAD signaling.

Oral encapsulated transforming growth factorβ1 reduces endogenous levels:Effect on inflammatory bowel disease

BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is in development as a novel treatment for inflammatory bowel disease(IBD).AIM To measure TGFβlevels in blood and tissue after oral administration of encapsulated TGFβ.METHODS Animals were orally administered encapsulated TGFβby gavage.Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.RESULTS We made the surprising discovery that oral administration of TreXTAM dramatically(approximately 50%)and significantly(P=0.025)reduced TGFβlevels in colon,but not small intestine or mesenteric lymph nodes.Similarly,levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM,or microencapsulated TGFβalone(denoted as TPX6001)were significantly(P<0.01)reduced from baseline levels.When tested in the SCID mouse CD4+CD25-adoptive cell transfer(ACT)model of IBD,oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.CONCLUSION These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβresults in reduced local and systemic levels of the active form of TGFβ.Our findings suggest potential clinical implications for use of encapsulated TGFβ,perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβsignaling.

Shenqihuatan formula(参七化痰方) reduces inflammation by inhibiting transforming growth factor-beta-stimulated signaling pathway in airway smooth muscle cells

OBJECTIVE:To study the effects and mechanism of Shenqihuatan formula(参七化痰方,SQHT)of the transforming growth factor-beta(TGF-β)-stimulated cell processes in airway remodeling.METHODS:The current study examined cell viability using a Cell Counting Kit-8 assay.Furthermore,a Transwell assay was conducted to detect the ability of cell migration,and apoptosis was detected via flowcytometry.Western Blot and quantitative real-time polymerase chain reaction(q RT-PCR)were used to determine the expression levels of apoptosis or inflammation-related factors,such as TGF-β,Interleukin-1β(IL-1β),B cell lymphoma 2(Bcl-2),Bcl-2-Associated X(Bax),Ras homolog gene family,member A(Rho A),recombinant rho associated coiled coil containing protein kinase 1/2(ROCK1/2),extracellular regulated protein kinases 1/2(ERK1/2),Snail,and Slug.Finally,the expression levels of matrix metalloproteinase-9(MMP-9)and Tissue inhibitor of metalloproteinase(TIMP-1)were admeasured by enzyme-linked immuno sorbent assay.RESULTS:The results demonstrated that SQHT inhibited the viability and migration,as well as the the F-actin formation and cytoskeletal reorganization of airway smooth muscle cells(ASMCs)stimulated by TGF-β.By monitoring the changes of critical regulators in the presence of the formula,it was observed that the expression levels of TGF-β,IL-1β,Bcl-2,Rho A,ROCK1/2,ERK1/2,Snail,and Slug were markedly suppressed,whereas Bax expression exhibited the opposite effect.Compared with a well-characterized Rho A pathway inhibitor,Fasudil,SQHT generated equivalent or even higher inhibitory effects on these processes in ASMCs.CONCLUSIONS:Collectively,these suggested that SQHT can reduce airway inflammation by inhibiting TGF-β-stimulated signaling pathways in ASMCs.These findings may provide a novel remedy for treating ASMC inflammation,which causes thickening and obstruction of the airway in chronic obstructive pulmonary disease.

结缔组织病相关间质性肺炎患者血清DKK-1,LTBP2水平表达与疾病活动度及对预后的相关性分析

目的分析结缔组织病(CTD)相关间质性肺炎(IP)患者治疗前后血清Dickkopf相关蛋白1(DKK-1)、潜在转化生长因子结合蛋白2(latent transforming growth factor binding protein 2,LTBP2)表达水平变化及其与疾病活动度和预后的关系。方法收集2022年1月~2023年10月河北北方学院附属第一医院收治的121例CTD患者,按照IP发生情况分为观察组(CTD相关IP患者,n=62)和对照组(CTD无IP患者,n=59);观察组依照疾病活动度分为稳定期组(n=26)和急性加重期组(n=36)。采用酶联免疫吸附试验(ELISA)检测血清DKK-1,LTBP2水平;采用Pearson或Spearman分析急性加重期CTD相关IP患者血清DKK-1,LTBP2水平与临床资料的相关性;采用Logistic回归分析CTD相关IP患者病情急性加重的影响因素。结果观察组血清DKK-1(14.98±3.32 ng/ml),LTBP2(32.64±4.01ng/ml)水平高于对照组(2.21±0.67 ng/ml,8.73±2.15 ng/ml),差异具有统计学意义(t=28.983,57.518,均P<0.05)。急性加重期组磨玻璃影占比(66.67%)、蜂窝影患者占比(52.78%)及血清DKK-1(19.67±4.10 ng/ml),LTBP2(38.76±4.92 ng/ml),C反应蛋白(CRP)(32.46±3.12 mg/L)水平高于稳定期组(30.77%,23.08%,8.48±1.37 ng/ml,24.17±3.65 ng/ml,22.05±2.80 mg/L),差异具有统计学意义(t/χ^(2)=7.790,5.534,13.362,12.781,13.524,均P<0.05)。急性加重期CTD相关IP患者治疗前血清DKK-1,LTBP2水平与磨玻璃影、蜂窝影、CRP,疾病活动度呈正相关(r=0.526,0.518,0.513,0.548;0.499,0.514,0.520,0.561,均P<0.05)。随着治疗时间延长,稳定期组和急性加重期组CTD相关IP患者血清DKK-1,LTBP2水平均下降,且治疗前、治疗1个月后、治疗3个月后急性加重期组血清DKK-1,LTBP2水平均高于稳定期组,差异具有统计学意义(t=13.355,13.206,15.913;12.781,12.263,11.161,均P<0.05)。DKK-1[OR(95%CI):2.458(1.297~4.657)],LTBP2[OR(95%CI):2.739(1.567~4.789)]是CTD相关IP患者病情急性加重的独立危险因素(均P<0.05)。结论CTD相关IP患者血清DKK-1,LTBP2水平显著升高,与疾病活动度密切相关,且治疗3个月后二者均明显下降,可一定程度监测患者治疗疗效。

PDGFR-β/TGF-β/Smad2/3信号通路调控阿尔茨海默病血脑屏障完整性和学习记忆能力的分子机制研究

目的:分析PDGFR-β/TGF-β/Smad2/3信号通路调控阿尔茨海默病(AD)血脑屏障(BBB)完整性和学习记忆能力的分子机制。方法:利用APP/PS1转基因AD小鼠模型,通过水迷路及觅食试验分析学习记忆能力;荧光免疫组织化学法检测海马区血管周细胞增殖率(ki67/desmin)、周细胞覆盖率(desmin/lectin);Western blot检测海马区血管周细胞TGF-βR1及其下游信号通路分子、紧密连接(TJs)蛋白的表达水平。经过外源性PDGF-BB脑室内注射和/或TGF-βR1激酶抑制剂SB431542腹腔内注射预处理后,分别进行上述分析。构建AD体外BBB模型,经过PDGF-BB和/或SB431542作用后,进行异硫氰酸荧光素-牛血清白蛋白(FITC-BSA)渗透性和跨细胞电阻检测。结果:与对照组相比,APP/PS1小鼠经过虚拟平台次数明显减少,达到终点所需时间明显延长(水迷路训练试验),投食区正确选择率明显下降(觅食训练试验);海马区desmin/lectin阳性细胞比例明显下降;TGF-βR1、p-Smad2、p-Smad3蛋白表达水平明显升高;TJs蛋白表达水平明显下降。外源性PDGF-BB可使APP/PS1小鼠经过虚拟平台次数明显增加、达到终点所需时间明显缩短(水迷路正式试验第28天)、投食区正确选择率明显提高(觅食正式试验第28天);海马区desmin/lectin阳性细胞比例明显增加;使TGF-βR1、p-Smad2、p-Smad3蛋白表达水平明显升高;使TJs蛋白表达水平明显升高。SB431542则可部分抑制上述作用。体外试验证明:外源性PDGF-BB可明显降低AD模型组的最终渗透系数,提高24 h时相对TEER值;SB431542则可部分抑制上述作用。结论:PDGFR-β/TGF-β/Smad2/3信号通路可通过诱导周细胞分化、覆盖,提高内皮细胞TJs的表达,调控AD血脑屏障完整性,以促进学习记忆能力恢复。

硫酸吲哚酚对心肌梗死模型小鼠心肌重构的影响

目的探讨硫酸吲哚酚(IS)对心肌梗死(myocardial infarction,MI)模型小鼠心肌重构的影响。方法C57BL/6J成年雄性小鼠50只,随机分为假手术组(Sham组)10只,硫酸吲哚酚组(Sham+IS组)10只,心肌梗死组(MI组)15只,心肌梗死+硫酸吲哚酚组(MI+IS组)15只。采用左前降支冠状动脉结扎术构建小鼠MI模型,术后第24小时,Sham+IS组和MI+IS组小鼠每天腹腔注射IS 100 mg/kg,Sham组和MI组每天腹腔注射等体积PBS,连续28 d,期间记录各组小鼠存活情况。实验第30天,心脏超声检查评估各组小鼠心脏功能,超高效液相色谱法检测各组小鼠血清中IS浓度,Masson染色评估各组小鼠梗死区心肌纤维化程度,RT-qPCR技术检测心肌组织α-sma、CollagenⅠ基因的表达水平,Western blot技术检测心肌组织TGF-β信号通路标记蛋白TGF-β、p-Smad2、p-Smad3的表达水平。结果实验第30天时,与MI组相比,MI+IS组小鼠存活率显著下降(χ^(2)=5.02,P<0.05)。与Sham组相比,Sham+IS组小鼠血清中IS浓度显著升高(t=54.87,P<0.05),与MI组相比,MI+IS组小鼠血清中IS浓度显著升高(t=38.55,P<0.05)。心脏超声检查示,Sham组和Sham+IS组的小鼠左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)无显著差异(P>0.05);与MI组相比,MI+IS组小鼠LVIDd、LVIDs显著增大(t=3.96、4.31,P<0.05),LVEF、LVFS显著降低(t=5.68、4.07,P<0.05)。Masson染色示,MI+IS组与MI组比较小鼠心肌间质胶原纤维沉积明显增多。RT-qPCR技术检测显示,MI+IS组与MI组相比,小鼠心肌组织α-sma、CollagenⅠ基因的表达水平显著升高(t=8.74、4.78,P<0.05)。Western blot方法检测显示,MI+IS组与MI组相比小鼠心肌组织中TGF-β、p-Smad2、p-Smad3蛋白的表达水平均显著升高(t=4.04~5.64,P<0.05)。结论IS可加重小鼠MI后病理性心肌重构,其机制可能与TGF-β信号通路激活相关。

Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish

Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.

Role of activin receptor-like kinase 1 in vascular development and cerebrovascular diseases

Activin receptor-like kinase 1(ALK1)is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta(TGFβ)receptor superfamily.ALK1 is specifically expressed in vascular endothelial cells,and its dynamic changes are closely related to the proliferation of endothelial cells,the recruitment of pericytes to blood vessels,and functional differentiation during embryonic vascular development.The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells.Indeed,mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation.Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms,arteriovenous malformations,and cerebral atherosclerosis.In this review,we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis,and we discuss its relationship to functional dysregulation in cerebrovascular diseases.This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis,treatment,and prevention.

Effects of insulin-like growth factor binding protein-related protein 1 in mice with hepatic fibrosis induced by thioacetamide

Background Insulin-like growth factor binding protein-related protein 1 （IGFBPrP1） can activate hepatic stellate cells and increase extracellular matrix （ECM） in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study. Methods Intraperitoneal injection of thioacetamide （TAA） is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, a-smooth muscle actin （a-SMA） and ECM in liver tissues, and the expression of transforming growth factor-β1 （TGF-β1） and Smad3. Data were statistically analyzed using one-way analysis of variance （ANOVA）, the SNK-q test for inter-group differences. Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased （P 〈0.01）, and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group （P 〈0.01）. The expression of hepatic IGFBPrP1, a-SMA, TGF-β1, Smad3, collagen 1 and fibronectin （FN） was significantly up-regulated in the TAA5w group （P 〈0.01）. Anti-IGFBPrP1 treatment reversed these changes （P 〈0.01）. Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM （namely, collagen I and FN）. The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.

冠状动脉粥样硬化性心脏病合并肺动脉高压患者血清ADMA、IL-6、TGF-β1水平检测意义

目的探讨冠状动脉粥样硬化性心脏病(CHD)合并肺动脉高压(PAH)患者血清不对称二甲基精氨酸(ADMA)、白细胞介素6(IL-6)、转化生长因子-β1(TGF-β1)水平,并分析其对CHD合并PAH的诊断价值。方法选取2019年6月至2022年6月郑州大学附属郑州中心医院收治的冠状动脉粥样硬化性心脏病(CHD)患者66例为研究对象,依据是否合并肺动脉高压(PAH)分为单纯CHD组22例、CHD合并PAH组44例,同期选取本院体检的健康志愿者132例为对照组。比较各组临床资料及不同组(入组时)、不同疾病严重程度患者血清ADMA、IL-6、TGF-β1水平。分析血清各指标与疾病严重程度、心肺功能相关性。分析血清各指标对CHD合并PAH的诊断价值。结果血清ADMA、IL-6、TGF-β1水平:CHD合并PAH组>单纯CHD组>对照组,重度>中度>轻度(P<0.05);ADMA、IL-6、TGF-β1与氨基末端B型脑钠肽前体(NT-proBNP)、肌钙蛋白I(cTnI)、肺动脉收缩压(sPAP)、肺动脉舒张压(dPAP)、疾病严重程度呈正相关(P<0.05);联合诊断CHD合并PAH的曲线下面积(AUC)大于单项诊断(P<0.05)。结论CHD合并PAH患者血清ADMA、IL-6、TGF-β1水平升高,且与病情严重程度相关,临床监测其水平变化诊断CHD合并PAH具有一定应用价值。

转化生长因子β_1在动脉粥样硬化形成中的作用及机制研究

目的 研究转化生长因子(TGF—β1)在动脉粥样硬化形成中的作用及机制。方法 用ELISA法测定冠心病患者血TGF—β1水平，并用人动脉血管平滑肌细胞作为对象,采用MTT法、^3H—胸腺嘧啶脱氧核苷(^3H—TdR)参入法、流式细胞分析仪观察TGF—β1对流产死胎胸主动脉血管平滑肌细胞增殖的作用及机制。结果 ①冠心病组的血清TGF—β1低于正常对照组；血管病变越严重，TGF—β1水平越低。②体外培养平滑肌细胞增殖活性(MTT法、^3H—TdR参入法)随TGF—β1浓度增加而逐渐减低，且与平滑肌细胞密度无关。③随着TGF—β1浓度的升高G1期细胞比例增加、G2期细胞比例减少。结论 TGF—β1能明显抑制平滑肌细胞的增殖，人体内血TGF—β1对动脉粥样硬化形成具有保护作用。

多因素损伤的老年性痴呆动物模型的实验研究

目的设计一种更贴近人类老年性痴呆(AD)病变特征的新的多因素模型,为研究AD的发病机制和药物开发提供理想的实验模型。方法SD雄性大鼠侧脑室内连续14d注入Aβ1～40,连续5d注入1％氯化铝溶液。首次注射时在丘脑前背侧核注入10ng TGFβ1。分别于术后1周和术后3个月取脑组织进行病理学染色,免疫组化方法检测ChAT和Aβ的活性。结果(1)模型鼠脑组织神经元排列紊乱、核固缩,刚果红染色阳性,3个月后出现老年斑和神经纤维缠结;(2)脑组织内ChAT活性降低,Aβ活性增加;(3)这些特征性改变持续时间长。结论本模型是一种由多种致病因素共同作用的新的、理想的AD动物模型。

瑞舒伐他汀辅治冠心病介入术后患者的疗效及其对血清IGF-Ⅰ、sE-selectin、TGF-β1水平的影响

目的观察瑞舒伐他汀辅治冠心病介入术后患者的疗效及其对血清胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、可溶性E选择素(sE-selectin)、转化生长因子-β1(TGF-β1)的影响。方法选择2014年6月-2015年6月广东医学院附属深圳宝安区中心医院社康科诊治的冠心病介入术后患者120例作为研究对象,根据抽签法随机分为观察组(n=60)及对照组(n=60)。对照组口服硫酸氢氯吡格雷片,观察组在对照组基础上加服瑞舒伐他汀,治疗2个月后比较2组临床治疗效果,治疗前后血脂水平、斑块大小及血清IGF-Ⅰ、sE-selectin、TGF-β1水平。结果观察组总有效率为96.67%,高于对照组的83.34%(X^2=5.926,P=0.015)。观察组血清sE-selectin水平低于对照组[(9.12±1.52)ng/ml vs.(22.78±3.48)ng/ml,t=23.31,P<0.05],而血清IGF-Ⅰ、TGF-β1水平高于对照组[(485.23±42.22)mmol/L vs.(375.25±36.69)mmol/L、(118.96±32.25)pg/ml vs.(85.69±22.52)pg/ml,t=12.743、5.481,P<0.05]。观察组治疗后TG、TC、LDL-C水平低于对照组[(2.06±0.76)mmol/L vs.(2.58±0.74)mmol/L、(4.05±0.62)mmol/L vs.(5.36±0.58)mmol/L、(3.45±0.70)mmol/L vs.(4.22±0.62)mmol/L,t=3.860、12.349、6.484,P<0.05],而HDL-C水平高于对照组[(2.88±0.65)mmol/L vs.(2.32±0.72)mmol/L,t=4.546,P<0.05]。观察组患者治疗后斑块面积、IMT水平低于对照组[(15.25±4.89)mmol/L vs.(22.02±5.66)mmol/L、(0.76±0.22)mm vs.(1.02±0.36)mm,t=7.127、4.852,P<0.05]。结论瑞舒伐他汀能有效调节冠心病介入术后患者血清IGF-Ⅰ、sE-selectin、TGF-β1水平,减轻动脉粥样硬化,提高患者治疗效果。

转化生长因子β1在风湿性心脏病心房颤动患者心房纤维化中的作用

目的观察转化生长因子β1(TGF-β1)在风湿性心脏病(风心病)心房颤动(房颤)患者心房组织中的表达情况,探讨其在风心病房颤心房纤维化中的作用及意义。方法38例风心病接受换瓣手术者于术中获取的右心耳分为3组,其中窦性心律组8例,阵发性房颤组10例,持续性房颤组20例。对各组心房组织,应用羟脯氨酸含量测定法及Mas-son染色检测胶原含量及分布;应用免疫组化技术检测TGF-β1蛋白表达及分布;应用RT-PCR检测TGF-β1 mRNA水平,应用Western blot检测TGF-β1的蛋白表达。结果TGF-β1主要表达在心肌细胞的细胞质;与风心病窦性心律组相比,TGF-β1的mRNA和蛋白表达及胶原含量在阵发性房颤组(P<0.05)和持续性房颤组均显著增加(P<0.01);与阵发性房颤组相比,持续性房颤组中TGF-β1 mRNA和蛋白表达及胶原含量继续明显增加(P<0.05)。相关分析发现TGF-β1的mRNA、蛋白表达程度与心房胶原含量均呈正相关(r=0.37,P<0.05;r=0.45,P<0.01)。结论风心病患者心房组织中TGF-β1的mRNA和蛋白表达上调可能是心房纤维化发生的分子机制之一,在风心病房颤的发生和维持中起一定的作用。

COPD模型大鼠肺组织TGF-β1 mRNA的表达及意义

目的探讨转化生长因子良（TGF-β1）在长期吸烟所致慢性阻塞性肺疾病（COPD）病理变化中的作用。方法将大鼠随机分为对照组和模型组，分别分为1-6月组，每组6只。建立大鼠吸烟COPD模型。光镜下观察吸烟对大鼠肺组织结构的影响，RT-PCR方法检测TGF-β1mRNA在肺组织中的表达。结果随吸烟时间延长，肺泡腔不规则扩大，肺泡间隔破裂，有的肺泡融合成肺大泡，以吸烟6月组最为明显，肺组织结构表明COPD模型建立成功。RT-PCR结果表明，TGF-β1mRNA在正常肺组织中呈微弱表达，随吸烟时间的延长，TGF-β1mRNA表达增多，5月组表达最多。结论长期吸烟可引起气道壁炎细胞浸润及肺组织形态学变化，导致COPD发生。TGF-β1，表达随吸烟月份增加逐渐增多，肺组织结构破坏与TGF-β1表达有相关性，表明TGF-β1在COPD的发生和发展过程中起重要作用。

肺泡Ⅱ型TGFβ_1和PDGF基因表达及其在肺纤维化中的意义

目的 :研究转化生长因子 β1(TGFβ1)和血小板源性生长因子 (PDGF)在肺泡Ⅱ型细胞中的表达及其在肺纤维化过程中的意义。方法 :分离培养正常成年大鼠肺泡Ⅱ型细胞 ,建立大鼠矽肺模型 ,用原位杂交和免疫组化技术检测体外培养的和矽肺病变中的肺泡Ⅱ型细胞TGFβ1和PDGF BmRNA和蛋白的表达。结果 :(1)体外培养的肺泡Ⅱ型细胞免疫组化染色TGFβ1强阳性 ,PDGF B弱阳性 ;原位杂交TGFβ1和PDGF BmRNA均为阳性。 (2 )大鼠矽肺实验组增生的肺泡Ⅱ型细胞明显表达TGFβ1和PDGF BmRNA和蛋白 ;对照组仅有部分正常肺泡Ⅱ型细胞TGFβ1mRNA呈弱阳性。结论 :增生的肺泡Ⅱ型细胞有TGFβ1和PDGF B基因表达 ,其在矽肺纤维化病变中可能起重要作用。

风湿性心脏病心房颤动患者心房组织碱性成纤维细胞生长因子及转化生长因子β_1的表达及意义

目的观察风湿性心脏病(风心病)心房颤动(房颤)患者心房组织中碱性成纤维细胞因子(bFGF)及转化生长因子β1(TGF-β1)的表达情况,并探讨其在风心病房颤心房纤维化中的作用及意义。方法将38例风心病二尖瓣病变接受换瓣手术者于术中获取的右心耳分为3组,其中窦性心律组8例,阵发性房颤组10例,持续性房颤组大于或等于6个月20例。应用羟脯氨酸含量测定法检测各组心房组织胶原含量;应用免疫组织化学技术检测各组心房组织中bFGF和TGF-β1的蛋白表达及分布。结果bFGF和TGF-β1主要表达在心肌细胞的胞质;与风心病窦性心率组相比,bFGF和TGF-β1表达及胶原含量在阵发性和持续性房颤组均显著增加(P<0.01);与阵发性房颤组相比,持续性房颤组中这两种细胞因子的表达及胶原含量继续明显增加(P<0.05)。bFGF和TGF-β1与胶原含量进行相关分析,发现bFGF及TGF-β1的表达程度与心房胶原含量均呈正相关,即随心房胶原含量的增加,bFGF(r=0.52,P<0.05)、TGF-β1(r=0.70,P<0.01)表达增强。结论风心病患者心房组织中bFGF和TGF-β1的表达上调可能是心房纤维化发生的分子机制之一,在风心病房颤的发生和维持中可能起重要作用。

早期药物干预对慢性阻塞性肺疾病大鼠转化生长因子β1的表达影响

目的 :观察慢性阻塞性肺疾病 (COPD)大鼠模型的 TGF- β1的表达变化和早期药物干预对其表达的影响。方法 :利用烟薰和气道内多次滴入脂多糖 (L PS)建立大鼠 COPD模型 (B组 )。早期给予冬虫夏草 (C组 ) ,红霉素(D组 ) ,吸入布地奈德 (E组 )等分组干预。小动物肺功能仪测定气道阻力 (RL)和动态顺应性 (Cdyn)。采用免疫组织化学法和逆转录 -聚合酶链反应 (RT- PCR)法检测 TGF- β1蛋白及 m RNA。结果 :模型组基本符合人类 COPD病理生理变化。外周细支气管平滑肌层和细胞外基质胶原较正常组 (A组 )大鼠明显增多。C组与 B组比 RL减少 (P<0 .0 1) ,D组、E组与 B组比 RL亦减少 ,但 Cdyn增加 (P<0 .0 1)。B组细支气管上皮、肺泡巨噬细胞和小动脉内皮的 TGF- β1蛋白及 m RNA的表达高于 A组 (P<0 .0 1) ,C组与 B组无明显差异 ,而 D组、E组与 B组相比 ,TGF- β1蛋白及 m RNA的抑制明显 ,主要表现在细支气管上皮 ,但两者抑制程度并无明显差异 (P>0 .0 5 )。气道阻力与细支气管黏膜上皮 TGF- β1蛋白 ,支气管肺组织的 TGF- β1m RNA均呈正相关 (r=0 .5 10、P<0 .0 1,r=0 .36 7、P<0 .0 5 )。结论 :慢性烟薰和气道内滴入 LPS能构建含有气道重塑特征的 COPD大鼠模型。早期应用红霉素 ,吸入布地奈德可明显抑制气道 TGF-