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为了探讨青蒿琥酯(artesunate,ART)对糖尿病视网膜病变组织中抗凋亡和细胞保护作用相关因子Bcl-2和热休克蛋白27(Hsp27)表达的影响,将30只健康雄性SD大鼠随机分为空白对照组(negative control)、模型对照组(model control)及药物治疗组(ART treated),其中模型对照组和药物治疗组给予注射链脲佐菌素(STZ)建立1型糖尿病大鼠模型,饲养3个月后,药物治疗组大鼠腹腔注射青蒿琥酯治疗10 d,分离三组大鼠视网膜,提取蛋白和总RNA。通过Western-blot,实时荧光定量PCR(RT-q PCR)对Bcl-2和Hsp27的表达情况进行检测。结果显示:Bcl-2在模型对照组中大鼠视网膜的表达下降(p<0.05),药物治疗组则显著增加(p<0.01);Hsp27在模型对照的表达量高于空白对照组(p<0.05),治疗组的表达量显著高于模型对照组(p<0.01)。结论经青蒿琥酯治疗后糖尿病大鼠视网膜组织中抗凋亡因子Bcl-2和细胞保护因子Hsp27表达均增强,减少糖尿病视网膜细胞凋亡,对神经细胞具有保护作用。
Abstract：To investigate the effects of expression on anti-apoptotic and cell protective effect related factor Bcl-2,heat-shock protein Hsp27, which were in the diabetic retinal pathological tissue, 30 healthy male SD rats were randomly divided into negative control, model control and ART treated groups. The model control group and ART treated group were given injection of streptozotocin(STZ) to establish the type 1 diabetic rat model. After being raised for 3 months, the ART treated rats' abdomina were given ART injection for 10 days. All retinas of three groups were isolated, total protein and RNA was extracted. The expression of Bcl-2 and Hsp27 was detected by Real-time PCR(RT-q PCR) and Western-blot. Result showed that the expression of Bcl-2 in model group was decreased(p<0.05),whereas in ART treated group was significantly increased(p<0.01). The expression of Hsp27 in model control group was significantly higher than in negative control group(p<0.05). And the expression of Hsp27 in ART group was significantly higher than in model control group(p<0.01). In conclusion, the expression of anti-apoptotic and cell protective effect related factor Bcl-2, heat-shock protein Hsp27 were all increased in diabetic rat retinal after being treated by ART, which can decrease the apoptosis of diabetic retinal cells and protect the nerve cells.
Barber A.J.,Lieth E.,Khin S.A.,Antonetti D.A.,Buchanan A.G.and Gardner T.W.,1998,Neural apoptosis in the retina dur ing experimental and human diabetes,Early on set and ef fect of insulin,Journal of Clinical Investigation,102783-791
Benakis A.,Paris M.,Loutan L.,Plessas C.T.,and Plessas S.T.1997,Pharmacokinetics of artemisinin and artesunate afte oral administration in healthy volunteers,American Journa of Tropical Medicine and Hygiene,56(1):17-23
Carper S.W.,Rocheleau T.A.,Cimino D.,and Storm F.K.,1997Heat shock protein 27 stimulates recovery of RNA and pro tein synthesis following a heat shock,Journal of Cellula Biochemistry,66:153-164
Chen B.H.,Jiang D.Y.,and Tang L.S.,2003,Advanced glycation end products induce apoptosis and expression of apoptoti genes in cultured bovine retinal capillary pericytes Zhonghua Yanke Zazhi(Chinese Journal of Ophthalmolo gy),39(4):224-227(陈百华,姜德咏,唐罗生,2003,糖基化终产物诱导牛视网膜周细胞凋亡与凋亡基因的表达中华眼科杂志,39(4):224-227)
Chen H.H.,and Zhou H.J.,2004,Inhibitory effects of artesunat on angiogensis,Yaoxue Xuebao(Acta Phamaceutica Sini ca),39(1):29-33(陈欢欢,周慧君,2004,青蒿琥酯的抗血管生成作用,药学学报,39(1):29-33)
Cheong J.W.,Chong S.Y.,Kim J.Y.,Eom J.I.,Jeung H.K.Maeng H.Y.,Lee S.T.,and Min Y.H.,2003,Induction o apoptosis by apicidin,a histone deacetylase inhibitor,via th activation of mitochondria-dependent caspase cascades in human Bcr-Abl-positive leukemia cells,Clinical Cancer Re search,9(13):5018-5027
Cooper L.F.,Uoshima K.,and Guo Z.Y.,2000,Transcriptiona regulation involving the intronic heat shock element of th rat hsp27 gene,Biochimica et Biophysica Acta,1490(3)348-354
Gao Y.,Wu J.H.,and Liu L.,2010,Streptozotocin-induced earl diabetic retinopathy model in rats,Dier Junyi Daxue Xuebao(Academic Journal of Second Military Medical University)31(10):1053-1059(高玉,吴晋辉,柳林,2010,链脲佐菌素诱发糖尿病大鼠早期视网膜病变模型的建立,第二军医大学学报,31(10):1053-1059)
Gardner T.W.,Antonetti D.A.,Barber A.J.,La Noue K.F.,and Levison S.W.,2002,Diabetic retinopathy:more than meet the eye,Survey of Ophthalmology,47(2):253-262
Garrido C.,Ottavi P.,Fromentin A.,Hammann A.,Arrigo A.P.Chauffert B.,and Mehlen P.,1997,HSP27 as a mediator o confluence-dependent resistance to cell death induced by anticancer drugs,Cancer Research,57(13):2661-2667
Gruden G.,Bruno G.,Chaturvedi N.,Burt D.,Schalkwijk C.Pinach S.,Stehouwer C.D.,Witte D.R.,Fuller J.H.,and Perin P.C.,2008,Serum heat shock protein 27 and diabete complications in the EURODIAB prospective complication study,Diabetes,57:966-1970
Guay J.,Lambert H.,Gingras-Breton G.,Lavoie J.N.,Huot J.and Landry J.,1997,Regulation of actin filament dynamic by p38 map kinase-mediated phosphorylation of heat shock protein 27,Journal of Cell Science,110:357-368
Huang W.,Fileta J.B.,Filippopoulos T.,Ray A.,Dobberfuhl A.and Grosskreutz C.L.,2007,Hsp27 phosphorylation in ex perimental glaucoma,Investigative Ophthalmology&Visu al Science,48:4129-4135
Li B.,and Zhang X.D.,2006,Advances in research on the molecu lar biology mechanisms of diabetic retinal pericyte cell apop tosis,Yanshiguangxue Zazhi(Chinese Journal of Optometr&Ophthalmology),8(2):131-133(李波,张学东,2006,糖尿病视网膜毛细血管周细胞凋亡分子生物学机制的研究进展,眼视光学杂志,8(2):131-133)
Li T.Y.,Sun G.G.,and Chen J.,2014,Analysis of effects on ra diabetic retinal vessels by Artesunate using perfusion of Evans blue in vivo,Dangdai Yiyao Luncong(Contemporar Medicine Forum),12(4):109-110(李铁英,孙国根,陈晶2014,用Evans蓝活体灌注血管造影技术观察青蒿琥酯对糖尿病大鼠视网膜血管病变影响的结果分析,当代医药论丛,12(4):109-110)
Li Y.,Roth S.,Laser M.,Ma J.X.,and Crosson C.E.,2003,Reti nal preconditioning and the induction of heat-shock protein27,Investigative Ophthalmology and Visual Science,441299-1304
Liu S.N.,Shao S.L.,Sui W.J.,Zhang W.W.,Zhao B.,and Chen W.W.,2015,Resveratrol Induces the apoptosis of human lung cancer A549 Cells,Jiyinzuxue Yu Yingyong Sheng wuxue(Genomics and Applied Biology),34(4):685-691(刘盛楠,邵淑丽,隋文静,张伟伟,赵彬,陈微微,2015,白藜芦醇诱导肺癌A549细胞凋亡,基因组学与应用生物学34(4):685-691)
Liu X.Z.,Xiao H.,Wang Z.B.,and Li R.X.,2001,A study on th apoptosis of capillary cells in early diabetic rats,Yank Yanjiu(Chinese Ophthalmology Research),19(1):35-38(刘学政,萧鸿,王中宾,李瑞祥,2001,糖尿病早期大鼠视网膜毛细血管细胞凋亡研究,眼科研究,19(1):35-38)
Luo L.H.,and Wang Y.L.,2008,Pathological changes of Diabet ic Retinopathy,Linchuang He Shiyan Yixue Zazhi(Journa of Clinical and Experimental Medicine),7(6):176-178(罗丽华,王艳玲,2008,糖尿病视网膜病变的病理改变,临床和实验医学杂志,7(6):176-178)
Matsushita H.,Morishita R.,Nata T.,Aoki M.,Nakagami H.Taniyama Y.,Yamamoto K.,Higaki J.,Yasufumi K.,and Ogihara T.,2000,Hypoxia-induced endothelial apoptosi through nuclear factor-B(NF-B)-mediated bcl-2 suppres sion:in vivo evidence of the importance of NF-B in en dothelial regulation,Circulation Research,89(9):974-981
Moore P.,E1-sherbeny A.,Roon P.,Schoenlein P.V.,Ganapathy V.,and Smith S.B.,2001,Apoptotic cell death in the mous retinal Ganglion cell layer is induced in vivo by the excitato ry Amino Acid Homocysteine,Experimental Eye Research73(1):45-57
Pan L.,Zhou S.P.,Guo Y.R.,and Li G.W.,2014,Experimenta study on programmed retinal cell death in diabetic rats Zhonghua Tangniaobing Zazhi(Chinese Journal of Dia betes),12(4):273-276(潘琳,周水平,郭艳茹,李光伟,2004糖尿病大鼠视网膜病变细胞凋亡的观察,中华糖尿病杂志,12(4):273-276)
Schmeer C.,Gamez A.,Tausch S.,Witte O.W.,and Isenmann S.2008,Statins modulate heat shock protein expression and enhance retinal ganglion cell survival after transient retina ischemia/reperfusion in vivo,Investigative Ophthalmology&Visual Science,49:4971-4981
Wang L.,Qi Y.Q.,and Li C.G.,2006,An analysis of risk factor of diabetic retinopathy in patients with type 2 diabetes,Qilu Yixue Zazhi(Medical Journal of Qilu),21(3):243-244(王娈,綦玉琴,李长贵,2006,2型糖尿病视网膜病变危险因素分析,齐鲁医学杂志,21(3):243-244)
Wang W.Q.,Zhou H.J.,Chen H.H.,and Wu G.D.,2004,Inhibito ry effect of artesunate on angiogenesis,Zhongguo Yaolixu yu Dulixue Zazhi(Chinese Journal of Pharmacology and Toxicology),18(1):32-36(王玮琴,周慧君,陈欢欢,吴国东,2004,青蒿琥酯抑制新生血管生成的作用,中国药理学与毒理学杂志,18(1):32-36)
Whitlock N.A.,Agarwal N.,Ma J.X.,and Crosson C.E.,2005Hsp27 up regulation by HIF-1 signaling offers protection a gainst retinal ischemia in rats,Investigative Ophthalmology and Visual Science,46:1092-1098
基本信息:
DOI：10.13417/j.gab.035.000248
中图分类号:R285.5
引用信息:
[1]李铁英,关晓海,曹福源,等.青蒿琥酯对糖尿病视网膜病变组织中Bcl-2和Hsp27表达的影响[J].基因组学与应用生物学,2016,35(02):248-253.DOI:10.13417/j.gab.035.000248.
基金信息:
河北省科技厅科技支撑计划项目(14277727D)资助
2016-02-25
2016-02-25