在本试验中,曲伏前列腺素作用后,设定对照组mRNA相对表达量为1作标准,6,12,24h组NF-кB p65mRNA相对表达量为0.492±0.100,0.515±0.173,0.784±0.030;免疫荧光半定量分析显示,对照组,6,12,24h组NF-кB p65荧光强度为176.65±4.34,119.90±12.54, 155.81±9.15,146.71±8.23,表现为睫状肌细胞内NF-кB表达在各时间组内明显降低;IкB初期改变不明显,24h后表达升高,6,12,24h组IkBɑ mRNA相对表达量为0.929±0.055,0.915±0.039,1.354±0.105,免疫荧光半定量分析显示对照组,6,12,24h组IкBɑ的荧光强度为107.62±7.26,99.16±8.67,94.82±5.33,129.67±8.08;并且对照组,6,12,24h组的磷酸化p65与p65的A比值均数分别为0.930±0.0235,0.870±0.086,0.748±0.012, 0.685±0.030,呈现磷酸化NF-кB p65含量随药物作用时间逐渐降低趋势,说明NF-кB p65的核易位受抑制。提示NF-кB在葡萄膜巩膜房水流出通道中可能起负调控作用。这可能与cAMP或cGMP抑制作用或细胞外基质的降解对其产生作用等多种调控机制有关。由于NF-кB广泛参与多种细胞因子和基因的转录调控,所以,NF-кB及其抑制因子IкB系统在葡萄膜巩膜通道中的上游及下游调控机制需进一步实验研究证实。
综上所述, NF-кB在曲伏前列腺素药物作用于人睫状肌细胞后,表现为表达下降,核易位受抑制,提示NF-кB在葡萄膜巩膜房水流出通道中起负调控作用。能否应用NF-кB抑制物增加葡萄膜巩膜房水流出,将为青光眼的药物治疗开辟新的途径。
【参考文献】 1 Mishima HK, Shoge K, Takamatsu M, Kiuchi Y, Tanaka J. Ultrasound biomicroscopic study of ciliary body thickness after topical application of pharmacologic agents. Am J Ophthalmol ,1996 ;121:319-321
2 Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination;The control of NF-κB activity. Annu Rev Immunol ,2000;18:621-663
3 Whiteside ST, Israel A. IkB proteins: Structure, function and regulation. Semin Cancer Biol ,1997;8:75-82
4 Minguet S, Huber M, Rosenkranz L, Adenosine and cAMP are potent inhibitors of the NF-kappa B pathway downstream of immunoreceptors. Eur J Immunol ,2005;35:25-30
5 Zhang Q, Li PH. Research advances on relationship between nudear factor-kB and glaucoma. Int J Ophthalmol(Guoji Yanke Zazhi) ,2006;6(4):840-843
6 Lindsey JD, To HD, Weinreb RN. Induction of c-fos by prostaglandin F2 alpha in human ciliary smooth muscle cells.Invest Ophthalmol Vis Sci ,1994;35(1):242-250
7 Anthony TL, Lindsey JD, Weinreb RN. Latanoprost's Effects on TIMP-1 and TIMP-2 Expression in Human Ciliary Muscle Cells. Invest Ophthalmol Vis Sci , 2002;43:3705-3711
8 Sagara T, Gaton D, Lindsey JD, Gabelt T, Kaufman PL, Weinreb RN. Topical prostaglandin F2( treatment reduces collagen Type I, III, and Ⅳ in the monkey eyes. Arch Ophthalmol , 1999;117:794-801
9 Chen J, Woodward DF. Prostanoid-induced relaxation of precontracted cat ciliary muscle is mediated by EP2 and DP receptors. Invest Ophthalmol Vis Sci ,1992;33(11):3195-3201
10 Chiao PJ, Miyamoto S, Verma LM. Autoregulation of IkBα proteolysis by the ubiquitin-proteasome pathway. Biochimie ,2001;83:351-356
11 Chase AJ, Bond M, Crook MF, Newby AC. Role of nuclear factor kappa B activation in Metalloproteinase-1, -3, and -9 secretion by human macrophages in vitro and rabbit foam cells produced in vivo. Arterioscler Thromb Vasc Biol ,2002;22(5):765-771
12 Moon MK, Kang DG, Lee JK, Kim JS, Lee HS. Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway. Life Sci ,2006;78(14):1550-1557
13 Yousufzai SY, Ali N, Abdel-Latif AA. Effects of adrenomedullin on cyclic AMP formation and on relaxation in iris sphincter smooth muscle. Invest Ophthalmol Vis Sci ,1999;40(13):3245-3253
14 Rahman A, Anwar KN, Minhajuddin M, Bijli KM, Javaid K,True AL, Malik AB. cAMP targeting of p38 MAP kinase inhibits thrombin-induced NF-kappaB activation and ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol ,2004;287(5):1017-1024
上一页 [1] [2] [3] [4] |