Antagonistic Effects of Tranilast on Proliferation and Collagen Synthesis Induced by TGF-β2 in Cultured Human Trabecular Meshwork Cells

Primaryopen angleglaucoma (POAG)isalead ingcauseofblindness ,whichinvolvesopticneuropa thyaccompaniedbycharacteristicvisualfielddefectsandisoftenassociatedwithelevatedintraocularpres sureduetodisturbanceofaqueoushumoroutflowthroughthetrabecularmeshwork …     

Transforming Growth Factor-β_2 Gene Cloning and Protein Expression in Human Trabecular Meshwork Cells

Primary open- angle glaucoma (POAG) is aleading cause of blindness,which involves optic neu-ropathy accompanied by characteristic visual field de-fects and is often associated with elevated intraocularpressure due to disturbance ofaqueoushumor outflowthrough the trabecularmeshwork (TM) .The patho-physiology of the TM in POAG has been character-ized by an increasein extracellularmatrix componentsand a decrease in the number of TM cells[1,2 ] .It hasbeen found that,compared with the non- P…     

Existence of Heme Oxygenase-carbon Monoxide-cyclic Guanosine Monophosphate Pathway in Human Trabecular Meshwork Cells In Vitro

To confirm the existence of heme oxygenase (HO)-carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HT-MCs) in vitro, and to evaluate the inductive role of heroin on this pathway, HTMCs of the third to fourth generation were cultured in vitro. Reverse transcripase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry.Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA,HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma.     

Effect of Transforming Growth Factor-β_2 on Phagocytosis in Cultured Bovine Trabecular Meshwork Cells

A gradual loss of cells occurs within the humantrabecular meshwork (TM) during normal aging andappears to be increased in patients with primary openangle glaucoma (POAG) [1] .The exactmechanism bywhich cells are lost in either condition is not known,however phagocytosis has been suggested[2 ] .It hasbeen found that,when compared with the non- POAGpatients,the level of transforming growth factor- β2(TGF- β2 ) which may be involved in the pathogenesisof POAG increased in the aqueous humo…     

原发性开角型青光眼小梁网内皮细胞凋亡的探讨

目的对比观察原发性开角型青光眼小梁网内皮细胞凋亡数目与正常尸眼小梁网内皮细胞凋亡数目的变化,并探讨其可能的发病机制。方法对16例20眼原发性开角型青光眼（观察组）手术中所切取的小梁组织与17例30眼正常尸眼（对照组）所切除的小梁组织,分别采用流式细胞术进行小梁网内皮细胞凋亡数目的测定,比较原发性开角型青光眼小梁网内皮细胞凋亡情况。结果通过实验发现原发性开角型青光眼小梁网内皮细胞凋亡比例（16％）明显高于正常尸眼小梁网内皮细胞凋亡（5％）。二者相比差异有统计学意义（P〈0．05）。结论原发性开角型青光眼小梁网对房水的滤过率下降,可能与小梁网内皮细胞凋亡数目的增多导致小梁网组织滤过功能的下降有一定的关系．     

Effect of Coiquhoumia Root on the Expression of Transforming Growth Factor-β in Mesangiai Proliferation Giomerulonephritis Model

Summary： To study the efficacy and the mechanism of Colquhoumia root （ Tripterygium hypoglaucure （Le,vL） Hutch） in the treatment of mesangial proliferation glomerulonephritis （MsPGN）, SD rats were injected with anti-thymoeyte serum （ATS） to make MsPGN model （anti-Thyl model）. The rats were then divided into 3 groups： normal control group, anti-Thyl model group and treatment group. Histopathologieal （HE, PAS）, immunohistoehemieal, RT-PCR technique and computer imaging analysis system were used to evaluate mesangial matrix production, the expression of TGF-β protein and mRNA in the tissues of kidney. Our result showed that proteinuria and the ratio of extraeellular matrix/glomerular capillaries area （ECM/CA） were increased significantly in model group. The expression of both TGF-β protein and mRNA in glomeruli was much higher in model group than in control group （P〈0.01）. After the treatment with Colquhoumia root, proteinuria, ECM/CA and the expression of both TGF-β1 protein and mRNA in glomeruli were significantly decreased in treatment group as compared with those in model group. It is concluded that Colquhoumia root is effective in reducing proteinuria and mesangial matrix proliferation in MsPGN and it may achieve these effects by inhibiting the expressions of TGF-β1 protein and mRNA of mesangial cells.     

压力对人眼小梁细胞自分泌TGF-β2的影响

目的 采用开放式压力控制培养系统研究压力对体外培养的人眼小粱细胞自分泌转化生长因子-β2（TGF-β2）的影响，探讨TGF-β2在原发开角型青光眼发病机制中的作用。方法 体外培养人眼小梁细胞并传至第5代。对照组不施加压力（0mmHg，1mmHg=0．133kPa），实验组施加20、40、60及80mmHg压力，分别持续0、12、24、36h。采用双抗体夹心酶联免疫吸附（ELISA）法测定细胞上清液中TGF-β2浓度。结果 小梁细胞自分泌TGF-β2随压力增高而增加，与对照组比较，差异有显著性意义（P〈0．05）；在20～60mmHg范围内，加压时间越长，TGF-β2增高越明显；虽然80mmHg压力水平下TGF-β2增高幅度下降，但加压12和24h组TGF-β2水平仍明显高于对照组（P〈0．05）。结论随压力增高，小梁细胞自分泌TGF-β2增多，其水平与压力大小及作用时问相关，推测TGP-β2分泌异常可能是原发开角型青光眼病理进程中的重要机制之一。     

转化生长因子—β2对牛眼小梁细胞吞噬功能的影响

观察转化生长因子β2(transforming growth factor-β2,TGF-β2）对体外培养牛眼小梁细胞吞噬功能的影响。体外培养牛眼小梁细胞经0、0．32、1．00、3．20ng/ml TGF-β2处理24h后，加入乳胶微粒，24h后作瑞氏染色，光镜下数取相邻20个细胞中的微粒数。结果发现：0．32、1．00、3．20ng/mlTGF－β2可促进牛眼小梁细胞吞噬乳胶微粒，与对照组比较有显著差异；同时呈现明显的量效关系。提示TGF－β2可促进牛眼小梁细胞的吞噬功能。     

Growth Inhibition and Apoptosis Induced by Retinoic Acid Combined with Interferon Alpha-2a on Transitional Cell Carcinoma of Bladder

To identify new favorable agents and develop novel approaches for the chemoprevention and treatment of superficial bladder cancer and invesligate the effects of combination of relinoids and interferon α-2a on growth inhibition and apoptosis induction in bladder cancer cell lines. Methods: Four bladder cancer cell lines, grade 1 to 3,and two retinoids, all-trans-retinoic acid(ATRA) ,9.cis retinoic acid(9cRA) ,combined with inteferon α-2a(INF),were used in the study.We compared the competence of these agents to inhibit growth, induce apoptosis, affect the exptession of nuclear retinoid receptors, and modulate STAT1 protein. Resu/ts: Most of the bladder cancer cell lines were resistant to the effect of ATRA and 9cRA on growth inhibition and apoptosis induction, even at higher concentration (10^-5M).The effects of ATRA and 9c RA on cell growth and apoptosis were enhanced by INF α-2a.Combination of ATRA and IFNa-2a induced ~ and Slat 1 expression in three bladder cancer cell lines, ~: The results demonstrated that INFw2a synergize with the inhibitory effect of ATRA and 9c RA on the growth intn‘bition and apoptosis of bladder cancer cells in vitro, which suggested that it has a potenlJal intexest for the trealment of transitimml cell carcinmna of bladder.     

大麻素WIN55,212-2对体外培养牛眼小梁细胞MMP-3、MMP-9及TIMP-1表达的影响

目的研究大麻素WIN55,212-2对体外培养的牛眼小梁细胞MMP-3、MMP-9及TIMP-1表达的影响,从而探讨其降眼压机制。方法采用组织块培养法对牛眼小梁细胞进行原代及传代培养,应用免疫组化方法（NSE,Ⅷ因子相关抗原染色）鉴定细胞,应用透射电镜对细胞进行形态学及生长特性观察;对传3代的小梁细胞分别施加含大麻素WIN55,212-2终浓度为0（对照组）、1、10、20、40μmol/L的培养液,48h后行MMP-3和MMP-9免疫组化SP染色,结果进行计算机图像分析并进行统计学检验。提取上清液用ELASA法检测随浓度的不同TIMP-1量的变化。结果体外培养的牛眼小梁细胞表达MMP-3及MMP-9,大麻素WIN55,212-2可促进MMP-3及MMP-9的表达,并抑制TIMP-1的表达。结论一定剂量的大麻素可以促进牛眼小梁细胞MMP-3及MMP-9的表达（P〈0.05）,并抑制TIMP-1的表达（P〈0.01）,从而达到降低眼压的目的。