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Cloning and Expression of Rat Transforming Growth Factor β1 cDNA in Osteoblasts 被引量:5
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作者 刘勇 郑启新 +3 位作者 杜靖远 曾晖 郭晓东 屈伸 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2000年第1期63-65,共3页
Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gen... Summary: Rat transforming growth factor β1 (rTGFβ1) cDNA from rat lymphocytes was cloned by RT-PCR and inserted into pcDNA3 to construct an eukaryotic expression vector, which was named pcDNA3-TGFβ1. The cloned gene was confirmed to code rat TGFβ1 by restriction enzyme analysis. pcDNA3-TGFβ1 plasmid was transfected into rat osteoblasts by using liposome-mediated gene transfer technique and the expression of TGFβ1 was detected by using irnmunohistochemical staining assay. It was found that the rat TGFβ1 expression product was obviously detectable in the transfected osteoblasts in 48 h. High expression of TGFβ1 was obtained in the rat osteoblasts in which the constructed TGFβ1 expression vector was transfected. 展开更多
关键词 transforming growth factor β1 gene expression RT-PCR OSTEOBLASTS molecular cloning
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Effects of Tanshinone ⅡA on Transforming Growth Factor β1-Smads Signal Pathway in Renal Interstitial Fibroblasts of Rats 被引量:1
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作者 唐锦辉 占成业 周建华 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2008年第5期539-542,共4页
The effects of tanshinone ⅡA (TSN) on transforming growth factor β1 (TGFβ1) signal transduction in renal interstitial fibroblasts of rats were studied in order to investigate its mechanism in prevention of rena... The effects of tanshinone ⅡA (TSN) on transforming growth factor β1 (TGFβ1) signal transduction in renal interstitial fibroblasts of rats were studied in order to investigate its mechanism in prevention of renal interstitial fibrosis. Rat renal fibroblasts of the line NRK/49F were cultured in vitro, stimulated with 5 ng/mL TGFβ1 and pretreated with 10-6, 10-5, 10-4 mol/L TSN respectively. The mRNA levels of fibronectin (FN) were examined by RT-PCR. The protein expression of FN and Smads was detected by Western blot. TGFβ1 induced the expression of FN mRNA and Smads in a time-dependent manner in a certain range. Compared with pre-stimulation, the FN mRNA and protein levels were increased by 1.1 times and 1.5 times respectively (P〈0.01, P〈0.01), and the protein expression of phosphorylated Smad2/3 (p-Smad2/3) increased by 7 times at the end of TGFβ1 stimulation (P〈0.01). TSN pretreatment may down-regulate the FN and p-Smad2/3 expression in a dose-dependent manner. 10-6 mol/L TSN pretreatment had no effect on the FN and p-Smad2/3 expression (both P〉0.05). After pretreatment with 10-5 and 10-4 mol/L TSN, the FN mRNA levels were decreased by 28.1% and 43.8% respectively (P〈0.05, P〈0.01), the FN protein levels were decreased by 40% and 44% respectively (P〈0.05, P〈0.05), and the p-Smad2/3 protein expression were decreased by 40% and 65% respectively (P〈0.05, P〈0.01). The inhibitory effect of TSN on renal interstitial fibrosis may be related to its blocking effect on TGFβ1-Smads signal pathway in renal intersti- tial fibroblasts. 展开更多
关键词 tanshinone A FIBROBLAST transforming growth factor β1 SMADS
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Effect of matrine on transforming growth factor β1 and hepatocyte growth factor in rat liver fibrosis model 被引量:9
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作者 Jian-Lan Yu Jun-Hua Li +3 位作者 Rong-Gui Cheng Yan-Mei Ma Xiao-Juan Wang Jing-Chun Liu 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2014年第5期390-393,共4页
Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly d... Objective:To observe the preventive and control effect of matrine on transforming growth factor(TCF- β1) and hepatocyte.growth factor(HCF) of liver fibrosis tissue in rals.Methods:A total of48 SD rats were randomly divided into A,B,C,D groups with 12 in each,group A as the normal control group and groups B.C,D as liver fibrosis models using composite modulus method with carbon tetrachloride(CCL_4).Group B was the model group,group C adopted γ— interferon lavage therapy in the second day of modeling,and group D adopted matrine lavage treatment,at 4 and8 weeks after treatment.Six rats were executed for detection of TGF- β1 and HGF,liver tissue histology and comparison fibrosis degree changes of rat liver tissue between groups.Results:Croups B,C,D showed a more significantly increased TCF- β1 at each time point compared with group A(P<0.05);Group B showed a more significantly increased TGF- β1 than groups C and D at weeks 4 and 8(P<0.05);group D showed a lowest level of TGF-β1,followed by groups C and B.HGF of group B decreased more significantly than A group at weeks 4 and 8(P<0.05);HGF of groups C and D was significantly elevated at 4 and 8 weeks than groups A and B(P<0.05),in which the group D showed the highest level of HGF.According to tissue histologic observation,rat liver tissue structure of group A was clear and normal,tissue structure of group B was destroyed with obvious fibrous tissue hyperplasia and fatty change of hepatic cells;groups C and D showed a slighter liver tissue damage,cell necrosis and connective tissue hyperplasia in collect abbacy than group B with a trend of obvious improvement.Conclusions:Matrine can reduce TGF- β1expression and enhance the activity of HGF,so as to realize the inhibition effect on liver fibrosis in rats. 展开更多
关键词 Liver FIBROSIS MATRINE TRANSFORMING GROWTH factor β1 HEPATOCYTE GROWTH factor
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Feedback regulation between phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 and transforming growth factor β1 and prognostic value in gastric cancer 被引量:3
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作者 Qi Shao Zhi-Ming Chen 《World Journal of Gastroenterology》 SCIE CAS 2020年第1期21-34,共14页
BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gast... BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gastric cancer remain unclear.AIM To evaluate the expression of PREX1 in gastric cancer and its significance in the development of gastric cancer,especially to evaluate the potential mechanism of PREX1 in gastric cancer.METHODS Bioinformatic analysis was performed in order to examine the expression of PREX1 in gastric cancer.The relationship between the survival rate of gastric cancer patients and PREX1 expression was assessed by Kaplan Meier portal.The Gene Set Enrichment Analysis and the correlation between PREX1 and transforming growth factor(TGF)β1 pathway-related mediators were evaluated by cBioPortal for Cancer Genomics.Western blotting and reverse transcriptase polymerase chain reaction assay were used to test the role of TGFβ1 on the expression of PREX1.Western blotting and dual-luciferase reporter system was used to evaluate the effect of PREX1 on the activation of TGFβ1 pathway.Wound healing and Transwell assay were used to assess the effect of PREX1 on the metastasis activity of gastric cancer cells.RESULTS PREX1 was overexpressed in the gastric tumors,and the expression levels were positively associated with the development of gastric cancer.Also,the high expression of PREX1 revealed poor prognosis,especially for those advanced and specific intestinal gastric cancer patients.PREX1 was closely involved in the positive regulation of cell adhesion and positively correlated with TGFβ1-related mediators.Furthermore,TGFβ1 could induce the expression of PREX1 at both the protein and mRNA level.Also,PREX1 could activate the TGFβ1 pathway.The induced PREX1 could increase the migration and invasion activity of gastric cancer cells.CONCLUSION PREX1 is overexpressed in gastric cancer,and the high level of PREX1 predicts poor prognosis.PREX1 is closely associated with TGFβsignaling and promotes the metastasis of gastric cancer cells. 展开更多
关键词 Phosphatidylinositol-3 4 5-trisphosphate dependent Rac exchange factor 1 Gastric cancer High expression Poor prognosis METASTASIS Transforming growth factorβ1 pathway
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大麻二酚对转化生长因子β1诱导肝星状细胞活化和肝纤维化的作用
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作者 王联 谢娜 +3 位作者 赵珮伶 陈浩 李芏酉 王豫萍 《中国组织工程研究》 CAS 北大核心 2025年第23期4965-4974,共10页
背景:大麻二酚具有抗炎、抗氧化等药理学作用,并且不具有精神活性,在肝脏疾病中的研究日渐增加,但其对肝星状细胞转化生长因子β1/Smad信号转导通路的作用尚未明确。目的:探讨大麻二酚对肝星状细胞中转化生长因子β1/Smad信号转导通路... 背景:大麻二酚具有抗炎、抗氧化等药理学作用,并且不具有精神活性,在肝脏疾病中的研究日渐增加,但其对肝星状细胞转化生长因子β1/Smad信号转导通路的作用尚未明确。目的:探讨大麻二酚对肝星状细胞中转化生长因子β1/Smad信号转导通路的影响,研究其抗肝纤维化的可能机制。方法:(1)体外实验:选取大鼠肝星状细胞株(HSC-T6),分6组培养:对照组常规培养24 h,单纯药物组加入大麻二酚培养24 h,造模组加入转化生长因子β1培养24 h,造模+低剂量药物组、造模+高剂量药物组、造模+阳性对照组均加入转化生长因子β1培养24 h后分别加入1,5μmol/L大麻二酚或水飞蓟素培养24 h。培养结束后,检测各组细胞α-平滑肌肌动蛋白与Ⅰ型胶原mRNA表达、白细胞介素1β与肿瘤坏死因子α水平及Ⅰ型胶原、转化生长因子β1/Smad信号转导通路蛋白表达。(2)动物体内实验:将C57BL/6J小鼠随机分为5组,每组8只:假手术组不造模,造模组、造模+低剂量药物组、造模+高剂量药物组、造模+阳性对照组通过胆管结扎法建立肝纤维化模型,造模3周后分别腹腔注射4,8 mg/kg大麻二酚或水飞蓟素,1次/d,连续给药7 d。给药结束后,检测各组小鼠肝功能、肝脏病理形态及α-平滑肌肌动蛋白、Ⅰ型胶原、转化生长因子β1/Smad信号转导通路相关蛋白表达。结果与结论:(1)体外实验:与对照组比较,造模组HSC-T6细胞α-平滑肌肌动蛋白与Ⅰ型胶原mRNA表达、白细胞介素1β与肿瘤坏死因子α水平以及Ⅰ型胶原、转化生长因子β1、p-Smad2/3蛋白表达均升高(P<0.05),Smad7蛋白表达降低(P<0.05);两种剂量大麻二酚处理可改善转化生长因子β1诱导的HSC-T6细胞上述指标的变化,并且以造模+高剂量药物组改善作用更明显;(2)体内实验:与假手术组比较,模型组小鼠血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶活性升高(P<0.05),肝组织中炎性细胞浸润及胶原含量增加(P<0.05),转化生长因子β1/Smad信号转导通路被激活,α-平滑肌肌动蛋白、Ⅰ型胶原蛋白表达升高(P<0.05);两种剂量大麻二酚干预可减轻造模小鼠上述指标的变化,并且以造模+高剂量药物组效果更明显;(3)结果表明,大麻二酚通过抑制肝星状细胞转化生长因子β1/Smad信号传导通路的激活抑制肝纤维化。 展开更多
关键词 大麻二酚 肝星状细胞 肝纤维化 信号转导通路 转化生长因子Β1/SMAD HSC-T6细胞
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GENE EXPRESSION OF TRANSFORMING GROWTH FACTOR β_1 TYPEII RECEPTOR IN HCC AND ITS CLINICAL SIGNIFICANCE
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作者 刘超 陈双 +1 位作者 王捷 区庆嘉 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1999年第2期139-141,共3页
Objective: Transforming Growth Factor-β1 (TGF-β1)plays a central role in the process of . growth suppressionof the hepatocytes, and its type II receptor (TGF-β1R II)transfers the signal of growth suppression. In th... Objective: Transforming Growth Factor-β1 (TGF-β1)plays a central role in the process of . growth suppressionof the hepatocytes, and its type II receptor (TGF-β1R II)transfers the signal of growth suppression. In this study,the gene expression of TGF-β1R II in HCC and itsclinical significance was investigated. Methods: Theexpression of TGF-β1R II mRNA in 30 cases Of HCCtissue and the surrounding liver tissue was separatelydetected using reverse transcription-PCR. Results:The positive expression rate of TGF-β1R II mRNA wassignificantly lower in HCC tissue (11/30) than that in thesurrounding liver tissue (23/30) (P<0.01). Further, theless the cancer tissue expressed TGF-β1R II mRNA, themore poorly the tumoral hepatocyte differentiated(P<0.01) and the more portal vein cancer embolusexisted (p=0.0465). Conclusion: The decreaseexpression of TGF-β1 R II mRNA by tumoral hepatocyteresults in the defect of its negative growth regulation,and this may be one of the most important reasons forits carcinogenesis and uncontrolled growth. 展开更多
关键词 Hepatocellular carcinoma Transforminggrowth factor1 receptor II Gene expression
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Transforming growth factor-β1 induces intestinal myofibroblast differentiation and modulates their migration 被引量:12
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作者 Julia Brenmoehl Sandra Nicole Miller +4 位作者 Claudia Hofmann Daniela Vogl Werner Falk Jrgen Schlmerich Gerhard Rogler 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第12期1431-1442,共12页
AIM: To investigate the effects of transforming growth factor β1 (TGF-β1) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro.METHODS: Primary CLPF cultures were in... AIM: To investigate the effects of transforming growth factor β1 (TGF-β1) on the differentiation of colonic lamina propria fibroblasts (CLPF) into myofibroblasts in vitro.METHODS: Primary CLPF cultures were incubated with TGF-β1 and analyzed for production of m-smooth muscle actin (α-SMA), fibronectin (FN) and FN isoforms. Migration assays were performed in a modified 48-well Boyden chamber. Levels of total and phosphorylated focal adhesion kinase (FAK) in CLPF were analyzed after induction of migration.did not change α-SMA levels, while TGF-β1 treatment for 6 d significantly increased α-SIVlA production. Short term incubation (6 h) with TGF-β1 enhanced CLPF migration, while long term treatment (6 d) of CLPF with TGF-β1 reduced migration to 15%-37% compared to untreated cells. FN and FN isoform mRNA expression were increased after short term incubation with TGF-β1 (2 d) in contrast to long term incubation with TGF-β1 for 6 d. After induction of migration, TGF-β1-preincubated CLPF showed higher amounts of FN and its isoforms and lower levels of total and phosphorylated FAK than untreated cells.CONCLUSION: Long term incubation of CLPF with TGF-β1 induced differentiation into myofibroblasts with enhanced α-SMA, reduced migratory potential and FAK phosphorylation, and increased FN production. In contrast, short term contact (6 h) of fibroblasts with TGF-β1 induced a dose-dependent increase of cell migration and FAK phosphorylation without induction of α-SMA production. 展开更多
关键词 Transforming growth factor β1 Colonicfibroblasts MYOFIBROBLASTS MIGRATION FIBRONECTIN
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Role of Transforming Growth Factor-β1 in the Process of Fibrosis of Denervated Skeletal Muscle 被引量:5
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作者 孟繁斌 陈江海 +5 位作者 刘娟 王旸 翁雨雄 陈燕花 李涛 陈振兵 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2011年第1期77-82,共6页
In order to investigate the biological function of transforming growth factor-β1(TGF-β1) during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastroc... In order to investigate the biological function of transforming growth factor-β1(TGF-β1) during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ(COL Ⅰ) mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection. 展开更多
关键词 transforming growth factor β1 DENERVATION muscle fibrosis
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血清胱抑素C、内皮素-1、转化生长因子-β1预测高尿酸血症患者非布司他治疗后疗效的价值 被引量:1
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作者 王岚 张懿芳 +3 位作者 武众众 李霞 赵斌燕 李楠 《临床和实验医学杂志》 2024年第9期937-941,共5页
目的研究血清胱抑素C、内皮素-1、转化生长因子-β1(TGF-β1)预测高尿酸血症(HUA)非布司他治疗后疗效的价值。方法回顾性分析2021年1月至2023年1月在武警山西总队医院收治的160例HUA患者的临床资料,所有患者均口服非布司他进行治疗,根... 目的研究血清胱抑素C、内皮素-1、转化生长因子-β1(TGF-β1)预测高尿酸血症(HUA)非布司他治疗后疗效的价值。方法回顾性分析2021年1月至2023年1月在武警山西总队医院收治的160例HUA患者的临床资料,所有患者均口服非布司他进行治疗,根据患者使用非布司他治疗3个月后的疗效情况分为有效组(n=118)和无效组(n=42)。观察两组基础资料信息[性别、年龄、体重指数、病程、疾病类型、合并高血压、合并糖尿病、血肌酐、肾小球过滤率(GFR)、血尿酸、胱抑素C、内皮素-1、TGF-β1水平]差异。采用多因素Logistic回归分析影响HUA患者非布司他治疗效果的危险因素。绘制受试者操作特征(ROC)曲线评估血清胱抑素C、内皮素-1、TGF-β1预测HUA患者非布司他治疗效果的效能。结果两组性别构成比、年龄、体重指数、病程、疾病类型、合并高血压、合并糖尿病、血肌酐、eGFR比较,差异均无统计学意义(P>0.05);无效组的血尿酸、胱抑素C、内皮素-1、TGF-β1水平分别为(435.89±33.05)μmol/L、(10.84±1.65)mg/L、(32.81±5.55)ng/L、(25.74±4.85)ng/mL,均显著高于有效组[(351.85±24.76)μmol/L、(8.15±1.43)mg/L、(24.56±4.12)ng/L、(19.28±3.62)ng/mL],差异均有统计学意义(P<0.05)。经多因素Logistic回归分析证实,血清血尿酸、胱抑素C、内皮素-1、TGF-β1高水平均是影响HUA患者非布司他治疗无效的危险因素(P<0.05)。经ROC分析证实,血清胱抑素C、内皮素-1、TGF-β1可用于HUA患者非布司他治疗效果的预测,曲线下面积分别为0.917、0.853、0.825,预测价值较好(P<0.05)。结论血清血尿酸、胱抑素C、内皮素-1、TGF-β1高水平均是影响HUA患者非布司他治疗效果的危险因素,可将以上指标作为评估HUA患者非布司他治疗效果的标志物,为临床降低HUA治疗无效风险提供参考。 展开更多
关键词 高尿酸血症 非布司他 血清胱抑素C 内皮素-1 转化生长因子-Β1
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转化生长因子-β1联合腺苷脱氨酶、GeneXpert MTB/RIF在结核性胸膜炎诊断中的应用观察 被引量:1
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作者 王霞 张利利 +3 位作者 李晓阳 韩伟 谭磊 姜玉华 《实用医院临床杂志》 2024年第2期50-53,共4页
目的观察转化生长因子-β1(TGF-β1)联合腺苷脱氨酶(ADA)、GeneXpert MTB/RIF在结核性胸膜炎(TPE)诊断中的应用效果。方法选取2020年8月至2022年8月因渗出性胸腔积液来我院就诊的患者220例,病理检查最终确诊为TPE 92例(TPE组),细菌性胸... 目的观察转化生长因子-β1(TGF-β1)联合腺苷脱氨酶(ADA)、GeneXpert MTB/RIF在结核性胸膜炎(TPE)诊断中的应用效果。方法选取2020年8月至2022年8月因渗出性胸腔积液来我院就诊的患者220例,病理检查最终确诊为TPE 92例(TPE组),细菌性胸腔积液(BPE)68例(BPE组),恶性胸腔积液(MPE)60例(MPE组),测定胸腔积液TGF-β1、ADA,并对胸腔积液进行GeneXpert MTB/RIF检测,比较三组检测结果,分析胸腔积液TGF-β1、ADA单独及联合检测对TPE的诊断价值并确定最佳截断值,分析TGF-β1、ADA、GeneXpert MTB/RIF单独及联合诊断TPE与病理诊断的一致性。结果三组胸腔积液TGF-β1及ADA水平比较,TPE组均为最高,其次是BPE组,MPE组最低(P<0.05);ROC曲线显示,TGF-β1、ADA诊断TPE的最佳截断值分别为31.155 ng/L、28.495 U/L,对应的曲线下面积(AUC)分别为0.935、0.934,联合诊断AUC为0.987;TGF-β1、ADA联合诊断与病理诊断一致性Kappa值为0.76,GeneXpert MTB/RIF单独诊断Kappa值为0.71,联合诊断Kappa值为0.83。结论TPE患者胸腔积液TGF-β1、ADA均高于细菌性及恶性胸腔积液类型,GeneXpert MTB/RIF联合胸腔积液TGF-β1、ADA检测对TPE具有较高的诊断价值,与病理诊断一致性良好。 展开更多
关键词 转化生长因子-Β1 腺苷脱氨酶 GeneXpert MTB/RIF 结核性胸膜炎 诊断价值
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Relationship of Transforming Growth Factor-β1 and Arginase-1 Levels with Long-term Survival after Kidney Transplantation
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作者 Xiao-xiao DU Yu-liang GUO +5 位作者 Min YANG Yan YU Sheng CHANG Bin LIU Lan-jun CAI Zhong-Hua Klaus Chen 《Current Medical Science》 SCIE CAS 2018年第3期455-460,共6页
In this study, we compared the serum levels of transforming growth factor-β1 (TGF-β1), interleukin-10 (IL-10), and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-te... In this study, we compared the serum levels of transforming growth factor-β1 (TGF-β1), interleukin-10 (IL-10), and arginase-1 in long-term survival kidney transplant recipients (LTSKTRs) with those in short-term survival kidney transplant recipients (STSKTRs). We then evaluated the relationship between these levels and graft function. Blood samples were collected from 50 adult LTSKTRs and 20 STSKTRs (graft survival approximately 1-3 years post-transplantation). All patients had stable kidney function. The samples were collected at our institution during the patients' follow-up examinations between March 2017 and September 2017. The plasma levels of TGF-β1, IL- 10, and arginase- 1 were analyzed using enzyme-linked immunosorbent assays (ELISA). The levels of TGF-β1 and arginase-1 were significantly higher in the LTSKTRs than in the STSKTRs. The time elapsed since transplantation was positively correlated with the levels of TGF-β1 and arginase-1 in the LTSKTRs. The estimated glomerular filtration rate was positively correlated with the TGF-β1 level, and the serum creatinine level was negatively correlated with the TGF-β1 level. Higher serum levels of TGF-β1 and arginase-1 were found in LTSKTRs than in STSKTRs, and we found that TGF-β1 was positively correlated with long-term graft survival and function. Additionally, TGF-β1 and arginase-1 levels were positively correlated with the time elapsed since transplantation. On the basis of these findings, TGF-β1 and arginase- 1 may play important roles in determining long-term graft survival. Thus, we propose that TGF-β1 and arginase-1 may potentially be used as predictive markers for evaluating long-term graft survival. 展开更多
关键词 transforming growth factor β1 arginase-1 long-term survival kidney transplant recipients estimated glomerular filtration rates serum creatinine
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入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与CHB肝纤维化严重程度的相关性及对疾病预后的预测价值 被引量:1
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作者 张艳敏 李登州 +1 位作者 陈秋芳 王海颖 《河南医学研究》 CAS 2024年第6期1002-1007,共6页
目的探讨入院时血清转化生长因子-β1(TGF-β1)、Smad同源蛋白2(Smad2)、Smad同源蛋白3(Smad3)及透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)水平与慢性乙型肝炎(CHB)肝纤维化严重程度的相关性及联合检测对疾病预... 目的探讨入院时血清转化生长因子-β1(TGF-β1)、Smad同源蛋白2(Smad2)、Smad同源蛋白3(Smad3)及透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)水平与慢性乙型肝炎(CHB)肝纤维化严重程度的相关性及联合检测对疾病预后的预测价值。方法选取河南省中医院2021年3月至2022年3月收治的78例CHB肝纤维化患者作为研究组,选择同期78名健康体检者作为对照组。比较研究组和对照组及不同肝纤维化分期、不同炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平与肝纤维化分期、炎症活动分级的相关性。CHB肝纤维化患者治疗3个月后,根据患者预后分为预后良好和预后不良亚组,比较预后良好和预后不良患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平联合检测对CHB肝纤维化患者预后不良的预测价值。结果研究组入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ高于对照组(P<0.05);不同肝纤维化分期、炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ比较:S1<S2<S3<S4、G1<G2<G3<G4,差异有统计学意义(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与肝纤维化分期、炎症活动分级均呈正相关(P<0.05)。预后良好患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平均低于预后不良患者(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平联合预测肝纤维化患者预后不良的曲线下面积(AUC)优于各指标单一检测(P<0.05)。结论CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平均呈现高表达,且与肝纤维化分期、炎症活动分级密切相关,其联合检测对CHB肝纤维化患者预后有较高的预测价值,可用于评估CHB肝纤维化患者病情严重程度和预后,为制定针对性治疗措施提供参考。 展开更多
关键词 慢性乙型肝炎 肝纤维化 转化生长因子-β1 Smad同源蛋白2 Smad同源蛋白3 透明质酸 Ⅲ型前胶原 层黏连蛋白 Ⅳ型胶原 严重程度 预后
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miR-19a调控TGF-β1/Smad信号通路对胃癌细胞增殖、侵袭及糖酵解的影响
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作者 单彪 卞良 +4 位作者 李书君 王佩显 吴殿超 雷秋香 刘登湘 《现代肿瘤医学》 CAS 2024年第22期4278-4284,共7页
目的:探究微小RNA-19a(miR-19a)通过调控转化生长因子-β1(TGF-β1)/Smad信号通路对人胃癌AGS细胞增殖、侵袭和糖酵解的影响。方法:体外培养人胃癌AGS细胞,采用脂质体进行转染分别将inhibitor NC、mimics NC、miR-19a inhibitor、miR-19... 目的:探究微小RNA-19a(miR-19a)通过调控转化生长因子-β1(TGF-β1)/Smad信号通路对人胃癌AGS细胞增殖、侵袭和糖酵解的影响。方法:体外培养人胃癌AGS细胞,采用脂质体进行转染分别将inhibitor NC、mimics NC、miR-19a inhibitor、miR-19a mimics转染至人胃癌AGS细胞记为inhibitor NC组、mimics NC组、miR-19a inhibitor组和miR-19a mimics组,不做转染处理的为对照组,通过实时荧光定量PCR(RT-qPCR)法检测miR-19a的表达量,用细胞计数试剂盒-8(CCK-8)检测细胞活力,发现敲低miR-19a可显著抑制胃癌AGS细胞活力。所以后续实验分为对照组、inhibitor NC组、miR-19a inhibitor组、抑制剂组(miR-19a inhibitor转染+10μmol/L TGF-β1/Smad通路抑制剂LY2109761)和激活剂组(miR-19a inhibitor转染+10μmol/L TGF-β1/Smad通路激活剂SRI-011381),采用RT-qPCR法、5-乙炔基-2'脱氧尿嘧啶核苷(EdU)、Transwell小室、乳酸、葡萄糖检测试剂盒及蛋白免疫印迹(WB)法分别对细胞miR-19a的表达、增殖率、侵袭数、乳酸含量、葡萄糖消耗水平及糖酵解、TGF-β1/Smad相关蛋白表达水平进行分析。结果:敲低miR-19a可显著抑制胃癌AGS细胞活力,所以选用转染miR-19a inhibitor进行后续通路验证实验。结果发现,对照组与inhibitor NC组在miR-19a的表达水平、细胞增殖率、侵袭数、葡萄糖消耗及乳酸水平、增殖细胞核抗原(PCNA)、己糖激酶2(HK2)、乳酸脱氢酶A(LDHA)、甘油醛-3-磷酸脱氢酶(GAPDH)、TGF-β1、p-Smad3蛋白表达水平等各项指标均无统计学差异(P>0.05)。miR-19a inhibitor组细胞miR-19a的表达、增殖率、侵袭数、葡萄糖消耗及乳酸水平、PCNA、HK2、LDHA、GAPDH、TGF-β1、p-Smad3蛋白水平低于inhibitor NC组(P<0.05)。抑制剂组细胞miR-19a的表达、增殖率、侵袭数、葡萄糖消耗及乳酸水平、PCNA、HK2、LDHA、GAPDH、TGF-β1、p-Smad3蛋白表达水平低于miR-19a inhibitor组,而激活剂组这些指标高于miR-19a inhibitor组(P<0.05)。结论:下调miR-19a可抑制人胃癌AGS细胞增殖、侵袭和糖酵解,其作用机制与阻滞TGF-β1/Smad信号转导有关。 展开更多
关键词 胃癌 微小RNA-19a 转化生长因子-β1/Smad 增殖 侵袭 糖酵解
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淡豆豉异黄酮调控TGF-β1/SnoN通路对糖尿病肾病小鼠肾组织的保护作用研究
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作者 刘科兰 周建华 +1 位作者 吴干斌 焦红军 《天津中医药》 CAS 2024年第8期1047-1054,共8页
[目的]观察淡豆豉异黄酮对糖尿病肾病(DKD)小鼠肾组织的保护作用,并探讨其对转化生长因子-β1(TGF-β1)/Smad核转录共抑制因子(SnoN)通路的调控作用。[方法]50只清洁级db/db小鼠和10只清洁级db/m小鼠,前者验证DKD建模成功后随机分5组,... [目的]观察淡豆豉异黄酮对糖尿病肾病(DKD)小鼠肾组织的保护作用,并探讨其对转化生长因子-β1(TGF-β1)/Smad核转录共抑制因子(SnoN)通路的调控作用。[方法]50只清洁级db/db小鼠和10只清洁级db/m小鼠,前者验证DKD建模成功后随机分5组,后者记为对照组。依那普利组予以依那普利10 mg/kg溶于0.1 mL/kg生理盐水中灌胃,淡豆豉异黄酮低、中、高剂量组分别予以12.5、25、50 mg/kg淡豆豉异黄酮溶于生理盐水中灌胃,其余组均予以生理盐水灌胃,均每日1次,共干预8周。己糖激酶法检测各组干预前、4周后、干预后空腹血糖(FBG),蛋白质定量(BCA)法检测24 h尿蛋白;检测血肌酐(Scr)、血尿素氮(BUN)、TGF-β1水平;干预后处死小鼠并取肾组织,观察肾组织病理;实时-逆转录聚合酶链反应(RT-qPCR)检测各组肾组织TGF-β1、Smad2/3、Smad7、SnoN信使核糖核酸(mRNA)表达;检测肾组织TGF-β1、Smad2/3、Smad7、SnoN蛋白表达及磷酸化-Smad2/3(p-Smad2/3)。[结果]模型组4周后、干预后FBG、24 h尿蛋白、Scr、BUN、TGF-β1水平均高于正常组(P<0.05),依那普利组24 h尿蛋白、Scr、BUN、TGF-β1水平和淡豆豉异黄酮低、中、高剂量组FBG、24 h尿蛋白、Scr、BUN、TGF-β1水平均低于模型组(P<0.05);模型组肾组织呈显著病理改变,依那普利组和淡豆豉异黄酮低、中、高剂量组病理改变和胶原纤维沉积均减轻;模型组肾组织TGF-β1 mRNA与蛋白表达、Smad2/3 mRNA表达与p-Smad2/3升高(P<0.05),依那普利组和淡豆豉异黄酮低、中、高剂量组均低于模型组(P<0.05);模型组肾组织Smad7、SnoN表达降低(P<0.05),依那普利组和淡豆豉异黄酮低、中、高剂量组均高于模型组(P<0.05)。淡豆豉异黄酮组的作用呈剂量依赖性,除FBG外淡豆豉异黄酮中剂量组上述定量指标与依那普利组差异均无统计学意义(P>0.05)。[结论]淡豆豉异黄酮可降低DKD小鼠血糖,减少24 h尿蛋白,保护肾功能,降低血清TGF-β1水平,减轻肾病变,下调TGF-β1、Smad2/3表达,降低p-Smad2/3水平,上调Smad7、SnoN表达。 展开更多
关键词 淡豆豉异黄酮 转化生长因子-Β1 Smad核转录共抑制因子 糖尿病肾病
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血清转化生长因子β1、白细胞介素-6、Toll样受体-4、核转录因子κB联合评估非小细胞肺癌放射性肺炎病情严重程度的价值
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作者 张静 毛英 《实用临床医药杂志》 CAS 2024年第14期12-17,共6页
目的探讨血清转化生长因子β1(TGF-β1)、白细胞介素-6(IL-6)、Toll样受体-4(TLR-4)和核转录因子κB(NF-κB)联合评估非小细胞肺癌(NSCLC)放射性肺炎(RP)病情严重程度的价值。方法选取104例NSCLC放疗后继发RP患者作为研究组,另选取52例N... 目的探讨血清转化生长因子β1(TGF-β1)、白细胞介素-6(IL-6)、Toll样受体-4(TLR-4)和核转录因子κB(NF-κB)联合评估非小细胞肺癌(NSCLC)放射性肺炎(RP)病情严重程度的价值。方法选取104例NSCLC放疗后继发RP患者作为研究组,另选取52例NSCLC放疗后未继发RP患者作为对照组。比较2组患者放疗前后血清TGF-β1、IL-6、TLR-4、NF-κB水平。比较研究组不同程度RP患者放疗前后血清TGF-β1、IL-6、TLR-4、NF-κB水平,分析各血清指标单独及联合评估NSCLC放疗后RP病情程度的价值。结果放疗结束后,研究组患者血清TGF-β1、IL-6、TLR-4、NF-κB水平均高于对照组,差异有统计学意义(P<0.05);放疗结束后,随着RP病情程度的增加,研究组患者血清TGF-β1、IL-6、TLR-4、NF-κB水平呈升高趋势,差异有统计学意义(P<0.05)。受试者工作特征(ROC)曲线分析结果显示,放疗结束后血清TGF-β1、IL-6、TLR-4、NF-κB水平评估1级RP的曲线下面积(AUC)分别为0.787、0.718、0.783、0.801,评估≥2级RP的AUC分别为0.729、0.740、0.793、0.825;血清TGF-β1、IL-6、TLR-4、NF-κB阳性表达患者发生≥2级RP的风险分别是阴性表达患者的2.473、2.275、2.610、5.267倍(P<0.05);血清TGF-β1、IL-6、TLR-4、NF-κB联合评估≥2级RP的AUC为0.939,敏感度为76.00%,特异度为97.47%。结论NSCLC患者放疗结束后血清TGF-β1、IL-6、TLR-4、NF-κB水平均与RP病情严重程度呈正相关,四者联合评估≥2级RP的价值显著,可为临床控制RP病情提供参考依据。 展开更多
关键词 非小细胞肺癌 放射性肺炎 转化生长因子β1 白细胞介素-6 TOLL样受体-4 核转录因子ΚB
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A型肉毒毒素防治额部外伤瘢痕的美学效果及对血清TGF-β_(1)、BMP-7水平的影响
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作者 彭梦龙 桂艳鸾 王荣 《中国美容医学》 CAS 2024年第6期30-33,共4页
目的:探讨A型肉毒毒素防治额部外伤瘢痕的美学效果及对血清TGF-β_(1)、BMP-7水平的影响。方法:选取2020年7月-2022年10月笔者医院收治的84例额部外伤患者为研究对象,按随机数字表法分为观察组和对照组,各42例。对照组采用清创美容缝合... 目的:探讨A型肉毒毒素防治额部外伤瘢痕的美学效果及对血清TGF-β_(1)、BMP-7水平的影响。方法:选取2020年7月-2022年10月笔者医院收治的84例额部外伤患者为研究对象,按随机数字表法分为观察组和对照组,各42例。对照组采用清创美容缝合联合外用硅凝胶制剂防治瘢痕;观察组采用美容缝合拆线后伤口两侧注射A型肉毒毒素防治瘢痕。拆线后3个月,统计比较两组瘢痕临床防治有效率、瘢痕评分[温哥华瘢痕量表(Vancouver scar scale,VSS)]、瘢痕疼痛或瘙痒程度评分[视觉模拟评分法(Visual analogue scale,VAS)]、患者满意度、血清转化生长因子β_(1)(Transforming growth factor-β_(1),TGF-β_(1))和骨成型蛋白7(Recombinant bone morphogenetic protein 7,BMP-7)水平及不良反应。结果:观察组VSS评分、瘢痕疼痛或瘙痒程度VAS评分低于对照组(P<0.05);观察组瘢痕临床防治有效率为90.47%,高于对照组的69.04%(P<0.05);观察组患者满意度高于对照组(P<0.05);观察组TGF-β_(1)水平低于对照组,BMP-7水平高于对照组(P<0.05);两组均未发生严重不良反应。结论:额部软组织外伤患者美容缝合拆线后伤口两侧注射A型肉毒毒素可抑制瘢痕形成,有效提升瘢痕防治有效率及患者满意度,其临床效果可能与调控血清TGF-β_(1)和BMP-7水平有关,且安全性较高,具有一定的临床应用价值。 展开更多
关键词 A型肉毒毒素 额部外伤 瘢痕 转化生长因子β_1 骨成型蛋白7
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血清LRG1、TGF-β1水平与急性脑梗死颈动脉内膜中层厚度及近期预后不良的关系
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作者 刘海花 王晓慧 +2 位作者 孙洪言 张露 吴丹 《国际检验医学杂志》 CAS 2024年第14期1725-1730,共6页
目的探讨血清富亮氨酸α-2糖蛋白-1(LRG1)、转化生长因子-β1(TGF-β1)水平与急性脑梗死(ACI)颈动脉内膜中层厚度(IMT)及近期预后不良的关系。方法选取2020年1月至2023年1月在苏州市广济医院诊治的123例ACI患者,根据IMT将患者分为正常组... 目的探讨血清富亮氨酸α-2糖蛋白-1(LRG1)、转化生长因子-β1(TGF-β1)水平与急性脑梗死(ACI)颈动脉内膜中层厚度(IMT)及近期预后不良的关系。方法选取2020年1月至2023年1月在苏州市广济医院诊治的123例ACI患者,根据IMT将患者分为正常组(23例)、增厚组(30例)和斑块组(70例),另选取同期苏州市广济医院35例体检健康者作为健康对照组,比较4组血清LRG1、TGF-β1水平及IMT。随访3个月,根据预后情况将患者分为预后良好组(75例)和预后不良组(48例),采用Pearson法分析血清LRG1、TGF-β1与IMT的相关性;采用单因素和多因素Logistic回归分析ACI患者近期预后不良的危险因素;采用受试者工作特征(ROC)曲线分析血清LRG1、TGF-β1水平对ACI患者近期预后不良的预测价值。结果健康对照组、正常组、增厚组、斑块组血清LRG1水平依次升高,TGF-β1水平则依次降低(P<0.05)。Pearson相关性分析显示,血清LRG1与IMT呈正相关,TGF-β1则与IMT呈负相关(P<0.05)。预后不良组年龄、合并糖尿病患者占比、入院美国国立卫生研究院卒中量表(NIHSS)评分、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、白细胞计数(WBC)、C-反应蛋白(CRP)及血清LRG1水平均高于预后良好组(P<0.05),发病至溶栓时间长于预后良好组(P<0.05),血清TGF-β1水平则低于预后良好组(P<0.05)。多因素Logistic回归分析显示,NIHSS评分高、发病至溶栓时间长、血清LRG1水平升高及TGF-β1水平降低均是影响ACI患者近期近期预后不良的危险因素(P<0.05)。ROC曲线结果显示,血清LRG1、TGF-β1单独及联合预测ACI患者近期预后不良的曲线下面积分别为0.824、0.708、0.902。结论ACI患者存在血清LRG1水平升高、TGF-β1水平降低的情况,血清LRG1、TGF-β1水平与IMT及ACI患者近期预后密切相关,联合检测血清LRG1、TGF-β1水平对预测ACI患者近期预后不良有较高的参考价值。 展开更多
关键词 急性脑梗死 颈动脉内膜 血清富亮氨酸α-2糖蛋白-1 转化生长因子-β1 近期预后
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活血利水复方对自发性高血压大鼠转化生长因子-β1/SMAD家族蛋白信号通路介导下游结缔组织生长因子及Ⅰ、Ⅲ型胶原表达及血管重塑的影响
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作者 莫霄云 刘丽云 +2 位作者 黄琛 廖博 林良广 《中医临床研究》 2024年第17期26-31,共6页
目的:基于转化生长因子-β1/SMAD家族蛋白信号通路探讨活血利水中药复方对自发性高血压大鼠血管重塑的保护作用及机制。方法:将自发性高血压大鼠随机分为模型组、卡托普利组、活血利水复方低剂量组、活血利水复方中剂量组、活血利水复... 目的:基于转化生长因子-β1/SMAD家族蛋白信号通路探讨活血利水中药复方对自发性高血压大鼠血管重塑的保护作用及机制。方法:将自发性高血压大鼠随机分为模型组、卡托普利组、活血利水复方低剂量组、活血利水复方中剂量组、活血利水复方高剂量组,Wistar大鼠作为空白组,每组10只。给予相应药物灌胃,4周后采用酶联免疫吸附试验方法检测血清中C反应蛋白、肿瘤坏死因子-α、白细胞介素-6的含量;采用逆转录聚合酶链反应检测大鼠主动脉组织转化生长因子-β1、结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原mRNA表达,并取冠状动脉组织进行马松三色染色。结果:与空白组比较,模型组血清中C反应蛋白、肿瘤坏死因子-α、白细胞介素-6的含量显著升高(P<0.01);与模型组比较,各药物组大鼠干预后血清中C反应蛋白、肿瘤坏死因子-α、白细胞介素-6的含量不同程度降低(P<0.01)。其中,卡托普利组和活血利水复方高剂量组上述3项指标表达最低,与其他组的差异有统计学意义(P<0.05或P<0.01);卡托普利组和活血利水复方高剂量组比较,差异无统计学意义(P>0.05)。与空白组比较,模型组大鼠主动脉转化生长因子-β1、结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原mRNA表达显著升高(P<0.01);与模型组比较,卡托普利组及活血利水复方低剂量组、活血利水复方中剂量组、活血利水复方高剂量组大鼠主动脉组织转化生长因子-β1、结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原mRNA表达不同程度降低(P<0.05或P<0.01)。结论:活血利水中药复方可通过调控转化生长因子-β1/SMAD家族蛋白信号通路及下游结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原mRNA表达水平,降低C反应蛋白、肿瘤坏死因子-α、白细胞介素-6等炎症因子的表达,抑制炎症反应,从而改善高血压病炎症状态及血管重塑,其机制可能与降低转化生长因子-β1、结缔组织生长因子及Ⅰ型胶原、Ⅲ型胶原蛋白沉积有关。 展开更多
关键词 活血利水中药复方 自发性高血压大鼠 转化生长因子-β1/SMAD家族蛋白信号通路 血管重塑
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输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平及临床意义
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作者 张林风 王晓倩 彭媛媛 《中国计划生育学杂志》 2024年第7期1621-1625,共5页
目的:分析输卵管阻塞性不孕患者血清转化生长因子-β1(TGF-β1)、白细胞介素-2(IL-2)、基质金属蛋白酶-9(MMP-9)水平变化及临床意义。方法:以本院2022年3月-2023年10月诊治的60例输卵管阻塞性不孕患者为病例组,正常妊娠分娩的女性50例... 目的:分析输卵管阻塞性不孕患者血清转化生长因子-β1(TGF-β1)、白细胞介素-2(IL-2)、基质金属蛋白酶-9(MMP-9)水平变化及临床意义。方法:以本院2022年3月-2023年10月诊治的60例输卵管阻塞性不孕患者为病例组,正常妊娠分娩的女性50例为对照组。测定对比两组血清TGF-β1、IL-2、MMP-9水平,Pearson相关性分析血清指标间相关性,受试者工作特征(ROC)曲线分析血清指标诊断不孕效能,logistic多因素回归分析输卵管阻塞性不孕发生影响因素。结果:病例组术前血清TGF-β1(593.79±148.23 ng/L)、IL-2(3.90±0.75 ng/L)、MMP-9(384.88±86.87 ng/ml)水平均高于对照组(239.42±113.37 ng/L、3.09±0.84 ng/L、178.98±80.85 ng/ml),术后血清TGF-β1、IL-2、MMP-9水平较术前均下降,血清TGF-β1与IL-2、MMP-9,及IL-2与MMP-9均呈正相关(均P<0.05)。ROC曲线分析,诊断不孕TGF-β1曲线下面积(AUC)0.941、敏感度88.3%、特异度94.0%,IL-2 AUC 0.778、敏感度66.7%、特异度84.0%,MMP-9 AUC 0.946、敏感度88.3%、特异度86.0%,3指标联合诊断AUC为0.992,敏感度93.3%、特异度100.0%。logistic回归分析,血清TGF-β1、IL-2、MMP-9异常升高是输卵管阻塞性不孕发发生的危险因素(均P<0.05)。结论:输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平均高表达,且是不孕发生的危险因素,3者联合检测对输卵管阻塞性不孕有较高诊断价值。 展开更多
关键词 输卵管阻塞性不孕 转化生长因子-Β1 白细胞介素-2 基质金属蛋白酶-9 危险因素 相关性 诊断
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雷帕霉素对人晶状体上皮细胞侵袭、迁移及炎症因子TNF-α、 IL-6、MIP-1α的影响
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作者 邱志方 张蝶念 易荣涛 《检验医学与临床》 CAS 2024年第14期2082-2088,共7页
目的探讨雷帕霉素(RAPA)对过氧化氢(H_(2)O_(2))诱导的人晶状体上皮细胞侵袭、迁移,以及对肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、巨噬细胞炎症蛋白-1α(MIP-1α)的影响。方法体外培养人晶状体HLE-B3细胞系,分为Con组、H_(2)O_... 目的探讨雷帕霉素(RAPA)对过氧化氢(H_(2)O_(2))诱导的人晶状体上皮细胞侵袭、迁移,以及对肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、巨噬细胞炎症蛋白-1α(MIP-1α)的影响。方法体外培养人晶状体HLE-B3细胞系,分为Con组、H_(2)O_(2)组、H_(2)O_(2)+RAPA组、Y组、RAPA+Y组和RAPA+A组。采用细胞计数试剂盒-8(CCK-8)测定细胞活力;采用酶联免疫吸附试验(ELISA)检测TNF-α、IL-6和MIP-1α表达水平;采用Transwell小室法检测细胞侵袭、迁移能力;采用实时荧光定量PCR(RT-qPCR)检测上皮间质转化(EMT)相关基因、蛋白的相对表达量;采用蛋白免疫印迹(WB)法测定EMT和转化生长因子-β(TGF-β)/Smads信号通路相关蛋白的相对表达量。结果细胞活力实验结果显示,选择50μmol/L的H_(2)O_(2)作为造模条件进行后续实验,选择20 nmol/L RAPA加入TGF-β1/Smads信号通路抑制剂LY2109761和激活剂SRI-011381进行TGF-β1/Smads信号通路验证实验。与Con组比较,H_(2)O_(2)组TNF-α、IL-6、MIP-1α表达水平,细胞迁移与侵袭能力,N-钙粘蛋白(N-cadherin)、波形蛋白(Vimentin)及纤维粘连蛋白(FN)的mRNA、蛋白相对表达量,TGF-β1、p-Smad3蛋白相对表达量均显著升高(P<0.05),E-钙粘蛋白(E-cadherin)的mRNA、蛋白相对表达量和Smad7蛋白相对表达量均显著降低(P<0.05);与H_(2)O_(2)组比较,H_(2)O_(2)+RAPA组和Y组TNF-α、IL-6、MIP-1α表达水平,细胞迁移与侵袭能力,N-cadherin、Vimentin及FN mRNA、蛋白相对表达量,TGF-β1、p-Smad3蛋白相对表达量均显著降低(P<0.05),E-cadherin mRNA、蛋白相对表达量和Smad7蛋白相对表达量均显著升高(P<0.05);与H_(2)O_(2)+RAPA组比较,RAPA+Y组TNF-α、IL-6、MIP-1α表达水平,细胞迁移与侵袭能力,N-cadherin、Vimentin及FN mRNA、蛋白相对表达量,TGF-β1、p-Smad3蛋白相对表达量均显著降低(P<0.05),E-cadherin mRNA、蛋白相对表达量和Smad7蛋白相对表达量均显著升高(P<0.05),RAPA+A组TNF-α、IL-6、MIP-1α表达水平,细胞迁移与侵袭能力,N-cadherin、Vimentin及FN mRNA、蛋白相对表达量,TGF-β1、p-Smad3蛋白相对表达量均显著升高(P<0.05),E-cadherin mRNA、蛋白相对表达量和Smad7蛋白相对表达量均显著降低(P<0.05)。结论RAPA可显著抑制H_(2)O_(2)诱导的人晶状体上皮HLE-B3细胞的侵袭、迁移能力,抑制EMT进程,并且缓解炎症反应,其作用机制可能与抑制TGF-β1/Smads通路的信号转导有关。 展开更多
关键词 白内障 晶状体上皮细胞 雷帕霉素 转化生长因子-β1/Smads信号通路 过氧化氢 侵袭 迁移 炎症因子
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