Expression of transforming growth factor-β_1 and its typeⅠ receptor in different phases of post-burn hypertrophic scars

Objective: To analyze and compare the expression pattern of the transforming growth factor-β1(TGF-β1) and its type I receptor (TGF-β RI ) in nounal human skin and various phases of post-burn hypertrophic scars (HTS). Method: The immunohistochemical ABC method was employed. Results: In nounal human skin, no evident immunoreactivity of TGF-β1 and TGF-β R I was observed. In activation phase of post-burn HTS, TGF-β R I and TGF-β1 were highly expressed in most dermal fibroblasts which seemed to be the same subset. However, in remission phase, no staining was seen in der mal fibroblasts. Conclusion: The formation of all may involve the increase of TGF-β responsiveness in fibroblasts The ac cumulation at the wound site and failure of apoptosis of over-resposive fibroblasts may contribute to the formation of HTS.

Expression of Mesenger RNA for Transforming Growth Factor-β_1 in Bovine Trabecular Meshwork

Purpose: To investigate the relationship between transforming growth factor-β1(TGF-β1) and primary open-angle glaucoma, we have determined whether trabec-ular tissues have the expression of messenger RNA for TGF-β1.Methods: Total RNA of 24 newborn bovine trabecular tissue were extracted byGuanidine isothiocyanate method. The TGF-β33 plasmid was brought into E. col-ibacillius HB101 and amplificated. After Bam HI endolase degradation and labelwith a-32p-dATP the RNA was hybridized with the cDNA (complementary DNA)probe and examined by autoradiography.Results: The presence of mRNA for TGF-β1 in bovine trabecular meshwork wasconfirmed.Conclusions: The TGF-β1 present in normal aqueous humor must be at least partlyderived from the trabecular meshwork. It offered a basis for understanding therelationship between abnormal synthesis, activation and clearance of TGF-β1 andthe pathogenesis of primary open-angle glaucoma (POAG) in molecular biology.Eye Science 1996; 12:1-4.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis

AIM To explore the role and mechanism of total flavone of Abelmoschus manihot(TFA) on epithelial-mesenchymal transition(EMT) progress of Crohn's disease(CD) intestinal fibrosis.METHODS First,CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial(IEC-6) cells and select the optimal concentrations of TFA for our further studies.Then cell morphology,wound healing and transwell assays were performed to examine the effect of TFA on morphology,migration and invasion of IEC-6 cells treated with TGF-β1.In addition,immunofluorescence,real-time PCR analysis(q RT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress.Moreover,western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways.Further,the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by q RTPCR,western blotting,morphology,wound healing andtranswell assays.RESULTS In this study,TFA promoted transforming growth factor-β1(TGF-β1)-induced(IEC-6) morphological change,migration and invasion,and increased the expression of epithelial markers and reduced the levels of mesenchymal markers,along with the inactivation of Smad and MAPK signaling pathways.Moreover,we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells.Importantly,co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSION These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

Histone deacetylase inhibitor suberoylanilide hydroxamic acid alleviates liver fibrosis by suppressing the transforming growth factor-β1 signal pathway

Background: Histone deacetylases(HDACs) inhibitors are new anti-fibrotic drugs that inhibit the activity of hepatic stellate cells. The present study focused on the anti-fibrotic function of HDAC inhibitor suberoylanilide hydroxamic acid(SAHA) by suppressing transforming growth factor-β1(TGF-β1) signaling. Methods: Male Sprague-Dawley rats were used to induce liver fibrosis with carbon tetrachloride(CCl 4) and LX2 cell(human hepatic stellate cell line) was stimulated by TGF-β1. Both animals and cells were treated with SAHA. The Smad7 and connective tissue growth factor(CTGF) mRNA levels were detected by real-time polymerase chain reaction(PCR). Western blotting was used to examine the protein levels of CTGF, Histone H3(H3), Smad7, Smad2/3, Acetyl-Histone H3(AH3), HDAC2, α-smooth muscle actin( α-SMA), HDAC6, p-Smad2/3 and HDAC8. In addition, the TGF-β1 and liver enzyme levels from rat serum were detected. Histopathological changes were examined by hematoxylin and eosin(HE), Sirius red and Masson trichrome staining. The α-SMA expression was detected by immumohistochemical staining. Results: Compared with control group, the TGF-β1 and liver enzyme levels from rat serum, together with the mRNA levels of CTGF and protein levels of CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were elevated in fibrotic rats( P < 0.01). But the Smad7 mRNA and AH3 protein levels were notably suppressed in the fibrotic rats( P < 0.01). Pathological examination showed the typical changes of liver fibrosis in the fibrotic rats. After the treatment with SAHA, the levels of liver enzymes, TGF-β1, CTGF, HDAC2, α-SMA, HDAC6, p-Smad2/3 and HDAC8 were reduced( P < 0.01) and Smad7 and AH3 protein contents were elevated in liver fibrotic rats( P < 0.01). Moreover, immumohistochemistry showed that SAHA significantly suppressed the α-SMA protein content in fibrotic liver( P < 0.01). Conclusion: The HDAC inhibitor SAHA alleviated liver fibrosis by suppressing the TGF-β1 signaling.

Hsa_circRNA_102610 upregulation in Crohn’s disease promotes transforming growth factor-β1-induced epithelial-mesenchymal transition via sponging of hsa-miR-130a-3p

BACKGROUND The incidence of inflammatory bowel disease,a chronic intestinal inflammatory disorder that includes Crohn’s disease(CD)and ulcerative colitis,is rising.Circular RNAs are considered valuable diagnostic biomarkers for CD.Current evidence supports the views that epithelial-mesenchymal transition(EMT)plays an important role in CD pathogenesis,and that hsa-miR-130a-3p can inhibit transforming growth factor-β1(TGF-β1)-induced EMT.Our previous study revealed that hsa_circRNA_102610 was upregulated in CD patients.Moreover,we predicted an interaction between hsa_circRNA_102610 and hsa-miR-130a-3p.Thus,we hypothesized that hsa_circRNA_102610 may play roles in the proliferation and EMT of intestinal epithelial cells by sponging hsa-miR-130a-3p to participate in the pathogenesis of CD.AIM To explore the mechanism of hsa_circRNA_102610 in the pathogenesis of CD.METHODS The relative expression levels of hsa_circRNA_102610 and hsa-miR-130a-3p in patients were detected by quantitative reverse transcription-polymerase chain reaction.The proliferation of human intestinal epithelial cells(HIECs)and normal-derived colon mucosa cell line 460(NCM460)cells was detected by cell counting kit-8,5-ethynyl-2’-deoxyuridine staining and cell cycle assays following overexpression or downregulation of hsa_circRNA_102610.Cell proliferation assays were performed as described above in a rescue experiment with hsa-miR-130a-3p mimics.The interaction of hsa_circRNA_102610 and hsa-miR-130a-3p was verified by fluorescence in situ hybridization and dual luciferase reporter assays.The relative expression levels of CyclinD1,mothers against decapentaplegic homolog 4(SMAD4),E-cadherin,N-cadherin and Vimentin were detected by western blotting following hsa_circRNA_102610 overexpression,TGF-β1-induced EMT or hsa-miR-130a-3p mimic transfection(in rescue experiments).RESULTS Upregulation of hsa_circRNA_102610 was determined to be positively correlated with elevated fecal calprotectin levels in CD(r=0.359,P=0.007)by Pearson correlation analysis.Hsa_circRNA_102610 promoted the proliferation of HIECs and NCM460 cells,while hsa-miR-130a-3p reversed the cell proliferationpromoting effects of hsa_circRNA_102610.Fluorescence in situ hybridization and dual luciferase reporter assays showed that hsa_circRNA_102610 directly bound hsa-miR-130a-3p in NCM460 and 293T cells.An inverse correlation between downregulation of hsa-miR-130a-3p and upregulation of hsa_circRNA_102610 in CD patients was observed(r=-0.290,P=0.024)by Pearson correlation analysis.Moreover,overexpression of hsa_circRNA_102610 promoted SMAD4 and CyclinD1 protein expression validated by western-blotting.Furthermore,overexpression of hsa_circRNA_102610 promoted TGF-β1 induced EMT in HIECs and NCM460 cells via targeting of hsa-miR-130a-3p,with increased expression of Vimentin and N-cadherin and decreased expression of E-cadherin.CONCLUSION Hsa_circRNA_102610 upregulation in CD patients could promote the proliferation and EMT of intestinal epithelial cells via sponging of hsa-miR-130a-3p.

Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate

BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.

Effects of Lingguizhugan Decoction on α-SMA and collagen synthesis in rat myocardial fibroblasts induced by transforming growth factor-β_(1)

Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.

Transforming growth factor beta-1 upregulates glucose transporter 1 and glycolysis through canonical and noncanonical pathways in hepatic stellate cells

BACKGROUND Hepatic stellate cells(HSCs)are the key effector cells mediating the occurrence and development of liver fibrosis,while aerobic glycolysis is an important metabolic characteristic of HSC activation.Transforming growth factor-β1(TGF-β1)induces aerobic glycolysis and is a driving factor for metabolic reprogramming.The occurrence of glycolysis depends on a high glucose uptake level.Glucose transporter 1(GLUT1)is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism,thus affecting cell proliferation and growth.However,little is known about the relationship between TGF-β1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs.AIM To investigate the mechanisms of action of GLUT1,TGF-β1 and aerobic glycolysis in the process of HSC activation during liver fibrosis.METHODS Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue.A Seahorse extracellular flux(XF)analyzer was used to examine changes in aerobic glycolytic flux,lactate production levels and glucose consumption levels in HSCs upon TGF-β1 stimulation.The mechanism by which TGF-β1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-β1/mothersagainst-decapentaplegic-homolog 2/3(Smad2/3)signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase(PI3K)/AKT signaling pathways.In addition,GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs.Finally,a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis.RESULTS GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues.In addition,immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins,indicating that GLUT1 expression was related to the development of liver fibrosis.TGF-β1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad,p38 MAPK and P13K/AKT signaling pathways.The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression.GLUT1 inhibition eliminated the effect of TGF-β1 on HSC proliferation and migration.A GLUT1 inhibitor was administered in a mouse model of liver fibrosis,and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis.CONCLUSION TGF-β1 induces GLUT1 expression in HSCs,a process related to liver fibrosis progression.In vitro experiments revealed that TGF-β1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs.In addition,in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.

Prognostic significance and relationship of SMAD3 phosphoisoforms and VEGFR-1 in gastric cancer:A clinicopathological study

BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Huangqi Decoction,a compound Chinese herbal medicine,inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-βaxis

Objective Huangqi Decoction(HQD),a classical traditional Chinese medicine formula,has been used as a valid treatment for alleviating liver fibrosis;however,the underlying molecular mechanism is still unknown.Although our previous studies showed that microRNA-663a(miR-663a)suppresses the proliferation and activation of hepatic stellate cells(HSCs)and the transforming growth factor-β/small mothers against decapentaplegic(TGF-β/Smad)pathway,whether long noncoding RNAs(lncRNAs)are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported.The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.Methods The expression levels of lnc-C18orf26-1,miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction.HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs.The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs.Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs.RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs.Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA.The expression levels of collagen α-2(I)chain(COL1A2),α-smooth muscle actin(α-SMA)and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.Results Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a.Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation,downregulated TGF-β1-stimulatedα-SMA and COL1A2 expression,and inhibited the TGF-β1/Smad signaling pathway.HQD suppressed the proliferation and activation of HSCs.HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs.Further studies showed that HQD inhibited the expression of COL1A2,α-SMA,TGF-β1,TGF-βtype I receptor(TGF-βRI)and phosphorylated Smad2(p-Smad2)in HSCs,and these effects were reversed by miR-663a inhibitor treatment.Conclusion Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis.HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.

急性脑梗死患者血清TGF-β_1检测的临床意义

目的 探讨血清转化生长因子 - β1 (TGF- β1 )在急性脑梗死 (ACI)发病过程中的变化及其意义。方法 采用酶联免疫吸附试验动态检测 35例 ACI患者血清 TGF- β1 浓度 ,分析其与梗死部位、大小、病情的相关性。结果 ACI患者血清 TGF- β1 浓度急性期降低 ,恢复期升高。皮质梗死组 TGF- β1 高于皮质下组 (P<0 .0 5 ) ;梗死体积大则 TGF- β1 浓度高 (P<0 .0 5 ) ;重型组 TGF- β1 浓度高于轻型组 ,但无统计学意义。梗死组中白细胞和单核细胞数高于对照组 (P<0 .0 5 )。结论 血清 TGF- β1 的产生与外周血白细胞总数有关 ,其浓度的改变与梗死部位、大小及病程有一定关系 ,提示 TGF- β1 是一种负性免疫调节剂。

EMT、TGF-β_1、Ang Ⅱ与器官纤维化发生机制的研究进展

纤维化是大多数慢性炎症性疾病的病理转归,几乎能发生在身体的每个组织器官。纤维化以过多的细胞外基质沉积为特征,进一步发展可导致器官功能衰竭乃至死亡。关于器官纤维化的研究很多,但其确切机制目前尚不明确。近年来,上皮间质转化(EMT)、转化生长因子β1(TGF-β1)、血管紧张素Ⅱ(AngⅡ)在组织器官纤维化形成机制研究中备受关注。该文就EMT、TGF-β1、AngⅡ与各器官纤维化的相互关系及作用机制予以综述,以更全面地认识纤维化的发生机制。

血清胱抑素-C及转化生长因子β_1在肾脏疾病中的检测及意义

目的:探讨肾脏疾病患者血清胱抑素 C(Cys C)及转化生长因子β1(TGF β1)的水平变化及与肾功能的关系。 方法:52例肾脏疾病患者根据Scr分为两组:甲组25例和乙组27例。采用免疫组化、ELISA法检测两组和22例 正常健康者(对照组)血清、尿Cys C及TGF β1的水平。检测结果采用SPSS统计软件进行统计学分析。结果:(1) 甲组与乙组、乙组与对照组血清BUN、Scr、Cys C及TGF β1差异均有显著性(P均<0.05)。血清BUN、Scr与 Cys C呈正相关(r=0.732,P<0.05;r=0.707,P<0.05);(2)尿中TGF β1水平与肾功能损害程度呈正相关(r= 0.640,P<0.05)。结论:在肾脏疾病中检测血清Cys C、尿TGF β1水平有助于评价肾脏功能,指导临床治疗。

二黄汤对哮喘模型大鼠肺组织中TGF-β_1及体内IL-33的影响

目的观察二黄汤对哮喘模型大鼠肺组织中转化生长因子β1(TGF-β1)及体内白介素-33(IL-33)的影响。方法 50只SD大鼠随机均分为正常组、哮喘组、布地奈德组、高剂量二黄汤组(含生药量68 g/kg)和低剂量二黄汤组(含生药量17 g/kg)。以卵清白蛋白致敏与激发建立哮喘大鼠模型,随后分别用布地奈德、二黄汤干预治疗。肺组织切片HE染色观察病理变化并检测气道管壁厚度(Wat)及气道平滑肌厚度(Wam),用免疫组化法检测肺组织TGF-β1蛋白的表达,酶联免疫法检测血清及支气管肺泡灌洗液(BALF)中IL-33的含量。结果所有药物干预组较哮喘组炎症细胞浸润明显减轻;布地奈德组、高剂量二黄汤组和低剂量二黄汤组Wat均较哮喘组下降(μm2/μm:54.99±8.82、52.28±7.61、58.53±7.63 vs 79.50±5.64,P<0.05);布地奈德组、高剂量二黄汤组和低剂量二黄汤组Wam均较哮喘组下降(μm2/μm:22.74±2.73、20.63±1.72、21.20±4.50 vs 30.16±1.68,P<0.05);与正常组比较,哮喘组BALF、血清中IL-33的浓度增高,经药物干预后,布地奈德组、高剂量二黄汤组和低剂量二黄汤组低于哮喘组(P<0.05),但3干预组间差异无统计学意义;哮喘组TGF-β1高于正常组(IOD:12.60±2.25 vs 1.67±0.17),布地奈德组(5.51±2.48)、高剂量二黄汤组(5.22±2.52)和低剂量二黄汤组(6.92±2.18)均低于哮喘组(P<0.05),3干预组间差异无统计学意义。哮喘大鼠的气道壁厚度和平滑肌厚度与TGF-β1、IL-33呈正相关。结论二黄汤可在一定程度上干预哮喘大鼠气道重塑,其作用可能是通过调节TGF-β1和IL-33实现的。

西维来司他钠对重症脑卒中患者血乳酸、CRP及TGF-β_(1)的影响研究

目的研究西维来司他钠对重症脑卒中患者血乳酸、C反应蛋白(CRP)以及转化生长因子β_(1)(TGF-β_(1))的影响。方法42例重症脑卒中患者,随机分为A组(19例)和B组(23例);A组患者接受综合治疗,B组患者在A组基础上加用西维来司他钠治疗。另选取15例轻症脑卒中患者作为C组。比较三组患者血乳酸、CRP及血TGF-β_(1)水平。结果治疗前及治疗2、7 d后,A组血乳酸分别为(2.81±0.96)、(2.23±0.77)、(1.85±0.52)mmol/L,CRP分别为(98.49±5.16)、(56.72±7.72)、(31.22±7.14)mg/L。治疗前及治疗2、7 d后,B组血乳酸分别为(3.08±0.87)、(2.31±0.85)、(1.78±0.63)mmol/L,CRP分别为(95.33±6.11)、(48.74±5.69)、(26.88±5.73)mg/L。C组血乳酸、CRP分别为(2.08±0.52)mmol/L、(18.34±5.88)mg/L。C组血乳酸低于A组和B组治疗前,差异具有统计学意义(P<0.05);C组CRP水平低于A组和B组治疗前及治疗2、7 d后,差异具有统计学意义(P<0.05);但A组和B组治疗前血乳酸、CRP水平比较差异均无统计学意义(P>0.05)。治疗2、7 d后,A组和B组血乳酸、CRP水平均低于本组治疗前,B组CRP水平低于A组,差异具有统计学意义(P<0.05);但A组和B组治疗2、7 d后血乳酸水平比较差异无统计学意义(P>0.05)。治疗前及治疗2、7 d后,A组血TGF-β_(1)分别为(92.16±20.25)、(112.09±35.92)、(183.04±21.22)μg/L,B组血TGF-β_(1)分别为(88.58±22.77)、(168.02±58.16)、(212.13±33.44)μg/L,C组血TGF-β_(1)为(110.25±20.46)μg/L。C组的血TGF-β_(1)水平高于B组和A组治疗前,差异具有统计学意义(P<0.05);A组和B组治疗前血TGF-β_(1)水平比较差异无统计学意义(P>0.05)。治疗2、7 d后,A组和B组血TGF-β_(1)水平均高于本组治疗前,且B组高于A组,差异具有统计学意义(P<0.05)。A组和B组治疗7 d后血TGF-β_(1)水平均高于C组,差异具有统计学意义(P<0.05)。结论西维来司他钠可以降低重症脑卒中患者血乳酸及CRP水平,提高血TGF-β_(1)水平,可改善重症脑卒中患者的预后。

The Role of TGF-β_1 in Mice Hepatic Fibrosis by Schistosomiasis Japonica

To investigate the role of transforming growth factor-β1 (TGF-β1) in mice with hepatic fi- brosis caused by Schistosomiasis Japonica, ELISA,VG staining and multimedia color hieroglyph quan- titative analysis were used to study the change of the serum TGF-β1, liver collagen fiber and reticular fiber in mice. The level of serum TGF-β1 in experimental group was significantly higher than that in control group (P<0.01 or P<0. 05) 8, 10, 12 weeks after infected by schistosomiasis. After infec- tion, the level of liver collagen fiber and reticular fiber, and that of TGF -β1 increased over time (P< 0.01 or P<0. 05). In mice infected by Schistosomiasis Japonica, the level of TGF-β1 increased with prolongation of infection time, and with the increase of liver collagen fiber and reticular fiber. TGFβ1 plays an important role of immunomodulation in hepatic fibrosis formation caused by Schistosomiasis Japonica.

Colonic expression of Runx3 protein and TGF-β_1 and their correlation in patients with irritable bowel syndrome

Objective:To investigate the role of Runx3 protein and TGF-β1 in the pathogenesis of irritable bowel syndrome（IBS）,as well as the correlation of these two proteins.Methods:Colonic tissue was collected from patients with IBS and normal persons.The colonic expression of Runx3 protein and TGF-β1 was detected with immunohislochemistry method.Semi-quantitative analysis was used to evaluate the staining degree of these two proteins.Results:Compared with their counterparts,patients with IBS did not show any changes in the colonic expression of Runx3 protein and TGF-β1（P】0.05）.Interestingly,there was a significant correlation between Runx3 protein and TGF-β1 in patients with IBS（P【0.05）.Conclusions:The role of Runx3 protein and TGF-β1 in the pathogenesis of IBS remains to be further studied.

Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-β1 in human pancreatic ductal adenocarcinoma

Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.

慢性心力衰竭患者血清转化生长因子-β_1和结缔组织生长因子水平与心功能关系

目的观察慢性心力衰竭(CHF)患者血清转化生长因子-β1(TGF-β1)和结缔组织生长因子(CTGF)的变化及与心功能相关性。方法收集105例CHF患者为CHF组,以68例健康查体者为健康对照组。检测血清TGF-β_1、CTGF水平及左心室射血分数(LVEF)、左心室质量指数(LVMI)变化,进行相关分析。结果 CHF患者血清TGF-β_1、CTGF均显著高于健康对照组(P均<0.01);TGF-β_1、CTGF升高与心力衰竭严重程度相平行;TGF-β_1、CTGF均与LVEF呈负相关(r=-0.638,P<0.01;r=-0.743,P<0.01),与LVMI(r=0.630,P<0.01;r=0.748,P<0.01)、心功能分级(r=0.647,P<0.01;r=0.753,P<0.01)呈正相关。结论血清TGF-β_1、CTGF共同参与了CHF的病理生理过程;血清CTGF水平可作为诊断及判断心力衰竭严重程度的生物学指标。