老龄大鼠肺内基质金属蛋白酶2、9及基质金属蛋白酶组织抑制因子1、2、3表达变化

目的:对比观察老龄大鼠和成年大鼠肺胶原蛋白的改变、转化生长因子β(transforming growth factor β,TGF-β)水平的变化、基质金属蛋白酶(matrix metalloproteinases,MMPS)MMP2,MMP9以及基质金属蛋白酶组织抑制因子(tissue inhibitor of metalloproteinases,TIMPS)表达调控的变化,寻找肺间质纤维化发病率随年龄增加的可能原因.方法:通过羟脯氨酸定量测定肺组织胶原含量,ELISA方法测定TGF-β1蛋白水平,荧光定量PCR(realtime PCR)技术测定MMP2,MMP9,TIMP1,TIMP2,TIMP3 mRNA表达量的变化.结果:与成年大鼠组相比,老龄大鼠肺细胞外胶原成分增加,TGF-β1蛋白水平升高[(756±160)pg/g vs(1 000±246)pg/g,P＜0.05],MMP2 mRNA(3.15±1.76 vs 0.17±0.13,P＜0.01)表达水平降低,MMP9 mRNA(1.66±0.67 vs 1.74±0.87,P＞0.05)表达水平没有明显变化.老龄大鼠组TIMP1 mRNA(2.00±1.74 vs 0.11±0.06,P＜0.01),TIMP2 mRNA(7.60±2.51 vs 2.69±1.76,P＜0.01),TIMP3 mRNA(1.32±0.46 vs 0.29±0.16,P＜0.01)表达水平均低于成年大鼠组.结论:肺老化后细胞外胶原比例增加,TGF-β1蛋白水平升高,MMP2和MMP9转录水平改变,TIMPS mRNA转录水平降低等多重因素共同构成肺间质纤维化发病率随年龄增加的基础.     

白介素-17与转化生长因子-β1在人脑胶质瘤组织中的表达及临床意义

目的 探讨人脑胶质瘤组织中白介素-17(IL-17)与转化生长因子β1(TGF-β1)表达的相关性及临床意义.方法 应用免疫组化二步法检测135例脑胶质瘤、15例正常脑组织中IL-17与TGF-β1的表达.结果 IL-17在正常脑组织中未见表达,在高、低级别胶质瘤中表达差异有统计学意义(P<0.01),其在高级别胶质瘤中的表达明显高于低级别胶质瘤.胶质瘤组织中TGF-131高表达77例,低表达58例,高表达率57.03%.高级别胶质瘤组织中TGF-β1的表达明显高于低级别(P＜0.05),正常脑组织中未见表达.胶质瘤组织中IL-17与TGF-β1表达呈正相关(r=0.285,P＜0.01).Kaplan-Meier生存分析提示IL-17、TGF-β1高表达组生存时间与低表达组生存时间差异有统计学意义(P＜0.01或P＜0.05).Cox模型多因素分析显示年龄、KPS评分、IL-17是影响胶质瘤患者术后生存时间的独立预后因素(P＜0.01).结论 人脑胶质瘤组织中IL-17的表达可能与TGF-β1有关.IL-17、TGF-β1的表达与人脑胶质瘤的恶性程度及预后相关.

Abstract：

Objective To investigate correlation between the amount of interleukin-17 (IL-17) producing cells and the expression of transforming growth factor (31 (TGF-β1) in glioma,and evaluate the clinical values of IL-17 and TGF-pl in predicting the prognosis of glioma. Methods The presence of IL-17 and TGF-pl was measured by immunohistochemistry in 135 human glioma (WHO Ⅰ 18,WHO Ⅱ 45,WHO Ⅲ 53,WHO Ⅳ 19) tissues and 15 normal brain tissues. Results There was no IL-17 positive staining in normal brain tissues. Of 135 glioma specimens showed low TGF-pl expression and 77 (57. 03% ) showed high TGF-pl expression. No TGF-β1 expression was detected in normal brain tissue. Furthermore,TGF-β1 expression was positively correlated with the amount of IL-17 producing cells in glioma tissues ( r=0.285, P<0.01). Compared with the low grade,the levels of IL-17 and TGF-pl positive cells were obviously increased in high grade. The Kaplan-Meier analysis showed that there were significant differences in overall survival (OS) between the IL-17 and TGF-pl high-expression and lowexpression group (P＜0.01, P＜0.05). The 3-year OS rates of IL-17 of high expression and low expression were 33.75% and 76. 36%. Multivariate Cox proportional hazards regression analysis indicated that age,KPS score, IL-17 were independent prognostic factor for OS (P＜0.01). Conclusion Intratumoral IL-17-producing cell density and the expression of TGF-β1 was associated with the malignancy of human glioma.     

基质金属蛋白酶-7与组织金属蛋白酶抑制剂-1在结直肠癌中的表达

目的 探讨结直肠癌组织中基质金属蛋白酶—7(MMP—7)及组织金属蛋白酶抑制剂—1(TIMP—1)表达的临床意义。方法 采用免疫组化法检测40例结肠直肠癌患者肿瘤组织和正常结直肠粘膜中MMP—7和TIMP—1的表达。结果 正常结直肠粘膜MMP—7和TIMP—1无阳性表达。本组40例中38例(95％)MMP—7阳性，TIMP—1阳性26例(65％)。MMP—7和TIMP—1阳性表达在有和无淋巴结转移组分别为100％、88．9和81．8％、44．5％(P＜0．05)。MMP—7和TIMP—1的阳性表达在A期 B期与C期 D期分别为88．8％、100％和56％、73％，但差异无显著性意义。结论 检测结直肠癌组织的MMP—7／TIM—1的表达有助于指导确立结直肠癌病人术后的随访和治疗方案。     

基质金属蛋白酶-9及其组织金属蛋白酶抑制剂-1表达与大肠癌侵袭转移的研究

目的:探讨基质金属蛋白酶-9(MMP鄄9)及其相应组织金属蛋白酶抑制剂-1(TIMP鄄1)在大肠癌组织中的表达与大肠癌侵袭转移的关系。方法:应用免疫组织化学SP法检测了48例大肠癌组织标本及23例正常大肠标本MMP鄄9、TIMP鄄1的表达。结果:48例大肠癌组织MMP鄄9阳性率为87.5%,显著高于正常大肠标本(P<0.05),伴有淋巴结转移或肝转移者MMP鄄9的阳性率明显高于无淋巴结转移或肝转移者(P<0.05)。大肠癌组织TIMP鄄1的阳性率为54.2%,明显高于正常大肠标本(P<0.05);MMP鄄9表达超过TIMP鄄1者,发生淋巴结转移和肝转移的比例明显高于TIMP鄄1表达超过MMP鄄9者。结论:MMP鄄9和TIMP鄄1表达失衡和大肠癌的浸润、淋巴结转移、肝转移密切相关,MMP鄄9有促进肿瘤侵袭转移的作用,TIMP鄄1和大肠癌的侵袭转移呈负相关;MMP鄄9表达超过TIMP鄄1者预后不良。     

Value of the pudendal nerves terminal motor latency measurements in the diagnosis of occult stress urinary incontinence

Background  Occult stress urinary incontinence may lead to de novo stress urinary incontinence after pelvic floor repair surgery. A measurement of pudendal nerve terminal motor latency can reflect the integrity of the nerves. We aimed to explore the value of pudendal nerve terminal motor latency in the diagnosis of occult stress urinary incontinence in pelvic organ prolapse patients.

Methods  Ten patients with stress urinary incontinence (SUI group), 10 with SUI and uterine or vaginal prolapse (POP+SUI group) and 10 with uncomplicated uterine or vaginal prolapse (POP group) were evaluated for their pudendal nerve terminal motor latency using a keypoint electromyogram.

Results  The amplitude of positive waves was between 0.1 and 0.2 mV. The nerve terminal motor latency was between 1.44 and 2.38 ms. There was no significant difference in the wave amplitudes of pudendal nerve evoked action potential among the three different groups (P >0.05). The pudendal nerve latency of the SUI group, POP+SUI group and POP group were (2.9±0.7) seconds, (2.8±0.7) seconds and (1.9±0.5) seconds respectively. The difference between the SUI group and POP+SUI group was not statistically significant (P >0.05), whereas the difference between the SUI and POP groups and between the POP+SUI and POP groups were statistically significant (P <0.05). There was a positive correlation between pudendal nerve latency and the severity of SUI; the correlation coefficient was 0.720 (P <0.01).

Conclusions  Patients with SUI may have some nerve demyelination injuries in the pudendal nerve but the damage might not involve the nerve axons. The measurement of pudendal nerve latency may be useful for the diagnosis of SUI in POP patients.

     

金属蛋白酶组织抑制因子-1、基质金属蛋白酶-9的表达与肾脏纤维化的关系

目的 :探讨基质金属蛋白酶 - 9(matrixmetalloproteinase - 9,MMP - 9)、金属蛋白酶组织抑制因子 - 1(tis sueinhibitorofmetalloproteinase - 1,TIMP - 1)在肾脏纤维化发生、发展中的意义。方法 :采用免疫组化技术和计算机图像分析系统检测不同病程肾脏疾病患者肾组织中TIMP - 1,MMP - 9及Ⅳ型胶原的表达情况 ,并以体视学多能目镜测试系统对肾活检病理切片进行形态计量 ,计算病变肾小管肾间质比率及肾小球硬化比率。结果 :肾脏病患者肾小管间质MMP - 9表达较正常呈显著增强 ,间质纤维化程度越重表达越弱 ;肾小管间质TIMP - 1表达、TIMP - 1/MMP - 9之比与病变肾小管肾间质比率呈显著正相关。结论 :肾脏病患者肾组织表达MMP - 9增高有助于消除过多的细胞外基质 (extracellularmatrix ,ECM ) ,是对肾组织纤维化形成的一种自身抑制效应 ;而TIMP - 1表达增高 ,导致ECM降解减少 ,参与肾组织纤维化的发生机制。     

肾透叨细胞癌中转化生长因子-β1、基质金属蛋白酶表达的临床观察

目的 探讨肾透明细胞癌中转化生长因子-β1、基质金属蛋白酶表达的临床价值.方法 采用免疫组化SP法测定60例肾透明细胞癌(RCCC)及30例正常肾组织中转化生长因子-β1(TGF-β 1)和基质金属蛋白酶(MMP2)的表达.结果 TGF-β 1和MMP2在RCCC中的阳性表达率为81.6%和86.7%,明显高于正常对照组,差异有统计学意义(P<0.05).TGF-β1和MMP2表达RCCC病理分级、临床分期呈明显正相关(P<0.01).结论 两者可作为反映RCCC生物学行为的指标,也可作为判断RCCC预后的分子指标.     

扛板归对肝纤维化大鼠肝组织基质金属蛋白酶-1基质金属蛋白酶-2及基质金属蛋白酶抑制剂-1表达的影响

目的:研究中药扛板归对二甲基亚硝胺诱导的肝纤维化大鼠肝组织中MMP -1,MMP -2及TIMP -1蛋白表达的影响.方法:用二甲基亚硝胺诱导大鼠肝纤维化模型,不同浓度扛板归干预后,取肝脏常规制片并HE染色,观察各组大鼠肝组织病理学改变,免疫组织化学方法检测各纽大鼠肝组织MMP -1,MMP -2及IMP -1蛋白表达的情况.结果:扛板归高、中剂量组中大鼠肝组织MMP -2及TIMP -1蛋白表达较模型组明显降低(P＜0.05),扛板归高、中剂量组中大鼠肝组织MMP-1蛋白表达较模型纽明显升高(P＜0.05).结论:扛放归具有显著的抗肝纤维化作用,其机制可能通过提高MMP -1表达,降低TIMP -1,MMP -2蛋白的表达而调控细胞外基质的代谢.     

Expression of transforming growth factor beta-1 in fibrosis of transplanted kidney

In order to study the role and significance of transforming growth factor beta-1 (TGF-β1)mRNA in transplanted renal fibrosis(TRF). Methods: Renal pathologic changes and expression of TGF-β1 mRNA were observed using in situ hybridization technique. The normal renal tissue as a control group. Results: Expression of TGF-β1 mRNA in the renal fibrosis increased, compared with that in the control group. The expression rate were co-related to the stage of TRF.Conclusion: TGF-β1 is related to the pathogenesis and development of TRF.     

Effect of Quyu Chencuo Formula(去菀陈莝方)on Renal Fibrosis in Obstructive Nephropathy Rats

Objective: To observe the effect of Quyu Chencuo Formula(去菀陈莝方, QCF) on renal fibrosis in rats with obstructive nephropathy. Methods: Twenty-four rats were randomly divided into three groups, 4 for sham operation as the control group, 10 for unilateral ureteral obstruction(UUO) model group, and the rest 10 for QCF treating UUO model group. All rats were sacrificed under 3% pentobarbital(50 mg/kg) anesthesia on the 14 th day after surgery, then the right kidney samples of rats were harvested for hematoxylin eosin(HE) staining and Masson staining to observe the renal pathological changes. Immunohistochemistry and Western blotting were used to examine the expression of transforming growth factor β1(TGF-β1), and real-time polymerase chain reaction(RT-PCR) was employed to examine the expressions of TGF-β1, α-smooth muscle actin(α-SMA) and E-cadherin mRNA. Results: HE and Masson staining showed that the renal interstitial of the rats in the control group had no significant fibrotic lesion; in the model group, there were obvious interstitial fibrosis; for the QCF group, there were epithelial cell necrosis, infiltration of lymphocytes and mononuclear cells, aggravated interstitial fibrosis in varied degrees, but the pathological changes were less in the QCF group than in the model group. The immunohistochemistry and Western blotting results showed that the TGF-β1 expression was increased significantly in the model group, while decreased significantly in the QCF group(P0.05); RT-PCR showed that the mRNA expression of α-SMA and TGF-β1 increased significantly in the model group, while both were significantly decreased in the QCF group compared with the model group(P0.05). The mRNA expression of E-cadherin was decreased significantly in the model group, and it was significantly increased in the QCF group as compared with the model group(P0.05). Conclusion: QCF may improve renal fibrosis by regulating the expressions of TGF-β1, α-SMA and E-cadherin, and prevent the progress of kidney fibrosis.     

基质金属蛋白酶-1及其组织抑制剂-1在子宫内膜异位症中的表达

目的 :评价基质金属蛋白酶 1(MMP 1)和基质金属蛋白酶组织抑制剂 (TIMP 1)在子宫内膜异位症 (EMs)中的表达 ,明确二者的相关性 ,探讨它们在EMs的发生、发展中的作用。方法 :用免疫组化检测MMP 1及TIMP 1在EMs的异位内膜组织 (6 4例 )及在位内膜组织 (4 0例 )中的表达 ,并与同期 32例子宫正常内膜组织进行对比。结果 :MMP 1在在位及异位内膜中均高表达 ,与正常内膜组织中的表达相比有统计学意义 (P <0 0 1) ;TIMP 1在异位及在位内膜中均呈低表达 ,与正常内膜组织中的表达有统计学意义 (P <0 0 1) ;异位内膜较在位内膜TIMP 1表达降低 (P <0 0 1)。结论 :异位内膜组织中的MMP 1过表达 ,而TIMP 1表达下降 ,两者间的比例失调使异位内膜组织更具侵袭性 ,这在EMs的发病机制中起着重要作用     

The Therapeutic Effects of Rehmannia Oral Liquid for the Syndrome of Heat Accumulation with Yin Consumption in Esophagus Cancer Patients Undergoing Radiotherapy——A Report of 60 Cases

Objective: To observe the clinical therapeutic effects of Rehmannia Oral Liquid on the syndrome of heat accumulation with Yin consumption in intermediate or late esophagus cancer patients undergoing radiotherapy. Methods: The IFN-α, TNF-α, IL-1β and TGF-β1 levels in sera were determined by the method of ABC-WLISA before and after the treatment with Rehmannia Oral Liquid. At the same time, the observation was carried out on the patient's general condition, symptoms and signs, barium meal or CT examinations, and biopsy. Another 30 cases of esophagus cancer were treated singly with radiotherapy as the control group. Results: Rehmannia Oral Liquid could obviously improve the patient's general condition, and the symptoms and signs after radiotherapy. Based on the X-ray examination and biopsy, the short-term local control rate of the treatment group and the control group was 70.0% and 40.0% respectively, showing a significant difference (P<0.05). Before the treatment, the level of serum IFN-α of both cancer groups was lower and the levels of TNF-α, IL-1β and TGF-β1 were higher than that of normal group. After treatment, the level of IFN-α in both treatment group and control group increased significantly (P<0.01), and the treatment group improved more obviously than the control group (P<0.05). The level of TNF-α of both groups decreased significantly (P<0.01) after treatment, and the level of IL-1β decreased in treatment group and increased in control group without the significant difference as compared with that before treatment. The level of TGF-β1 was significantly increased in control group (P<0.05) and decreased in treatment group (P>0.05) after treatment. The difference between groups was significant (P<0.05). Conclusion: Rehmannia Oral Liquid can obviously reduce the radiotherapy reaction, improve the quality of life, and raise the therapeutic effects. The action mechanism of the Liquid may lie in balancing the cytokine network and regulating the disordered signal transmission.     

TGFBR2、TGF-β1及CTGF在盆腔器官脱垂患者子宫韧带组织中的表达及意义

目的 研究转化生长因子β受体2(transforming growth factor β receptor 2,TGFBR2)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)及结缔组织生长因子(connective tissue growth factor, CTGF)在盆底器官脱垂(pelvic floor organ prolapse, POP)患者子宫韧带组织中的表达及意义。方法 选取山西医科大学第二医院妇产科2020年10月至2022年10月收治的20例POP患者子宫主韧带及骶韧带组织为POP组，另选取20例因子宫肌瘤同期在该院行腹腔镜下全子宫切除术患者的主韧带及骶韧带组织为对照组。HE染色观察子宫主、骶韧带胶原纤维及成纤维细胞状态，并使用Masson染色进一步观察胶原纤维形态，免疫蛋白印迹法(Western blot)检测TGFBR2、TGF-β1、CTGF、Ⅰ型胶原蛋白(CollagenⅠ)及Ⅲ型胶原蛋白(CollagenⅢ)的蛋白表达水平。另选取4例POP患者和5例子宫肌瘤患者骶韧带进行全基因转录组测序，从转录组测序结果中筛...     

胃管状腺癌组织中基质金属蛋白酶-2、组织金属蛋白酶抑制因子-2的表达

目的 :探讨胃管状腺癌组织中基质金属蛋白酶 - 2 (MMP - 2 )和基质金属蛋白酶抑制因子 - 2 (TIMP - 2 )的表达。方法 :采用免疫组化S -P法对 4 7例管状腺癌进行MMP - 2和TIMP - 2的检测。结果 :MMP - 2和TIMP -2均在胃癌细胞浆内呈阳性表达 ,阳性表达率分别为 2 1 .3%和 78.7% ;MMP - 2和TIMP - 2表达与胃管状腺癌淋巴结转移 (P <0 .0 5 )及浆膜浸润相关 (P <0 .0 5 )。结论 :MMP - 2和TIMP - 2表达可作为判断胃癌恶性行为重要生物学标志。     

Induction of chondrogenesis of adipose-derived stem cells by novel recombinant TGF-β3 fusion protein

A new type of TGF-β3 fusion protein with targeted therapy function was constructed,and its feasibility and target specificity of inducing chondrogenesis were investigated by transfecting LAP-MMP-mTGF-β3 gene into adipose-derived stem cells (ADSCs).The recombinant pIRESEGFP-MMP was constructed by inserting the sense and antisense DNA of encoding the amino acid of the synthetic MMP enzyme cutting site into the eukaryotic expression vector pIRES-EGFP.LAP and mTGF-β3 fragments were obtained by using RT-PCR and inserted into the upstream and downstream of MMP from pIRES-EGFP-MMP respectively,and the recombinant plasmid of pIRES-EGFPLAP-MMP-mTGF-β3 was constructed,which was transferred to ADSCs.The ADSCs were cultured and divided in three groups:experimental group (MMP group),negative control group (no MMP) and non-transfection group.The morphological changes were observed microscopically,and the expression of proteoglycan and type Ⅱ collagen (ColⅡ) was detected by using Alcian blue staining and immunohistochemistry staining at 7th,14th and 21st day after culture.The recombinant plasmid of pIRES-EGFP-LAP-MMP-mTGF-β3 was correctly constructed by methods of enzyme cutting and sequencing analysis.The mTGF-β3 fusion protein was successfully expressed after transfection,and in the presence of the MMP,active protein mTGF-β3 was generated,which significantly promoted differentiation of ADSCs into chondrocytes and the expression of cartilage matrix.The novel fusion protein LAP-MMP-mTGF-β3 can targetedly induce differentiation of ADSCs into chondrocytes,which would open up prospects for target therapy of cartilage damage repair in future.