脉通方对糖尿病性勃起功能障碍大鼠阴茎海绵体细胞凋亡及其相关因素的影响
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摘要
目的:观察脉通方对糖尿病性勃起功能障碍(DMED)大鼠阴茎海绵体组织细胞凋亡相关蛋白表达的影响,以及本方对DMED大鼠阴茎海绵体组织细胞超微结构的影响,为临床糖尿病并发症的防治提供理论依据。
方法:采用Sprague Dawley大鼠(SD大鼠)50只,适应性喂养1周后随机抽取10只作为正常组,其余40只采用小剂量多次腹腔注射链脲佐菌素(STZ)的方法造糖尿病大鼠模型,餐后2h血糖＞16.7mmol/l为DM成模;DM大鼠成模后正常饮食喂养15周后,每只大鼠用阿朴吗啡(APO)试验测定是否成糖尿病性勃起功能障碍(DMED)模,DMED大鼠成模后随机分组为治疗组、模型组;治疗组给以脉通方水煎液,模型组及正常组均给以等量蒸馏水,灌胃15天后断颈处死。观测一般状况、血糖、血清超氧化物歧化酶等指标以及海绵体组织细胞凋亡相关蛋白的表达,在光镜及电镜下分别观察海绵体组织超微结构的病理改变。
结果:按设计方案灌胃15后,治疗组血糖较模型组血糖降低,但仍高于正常组(p＜0.05);血清超氧化物岐化酶值治疗组与模型组差异无统计学意义(p＞0.05);凋亡抑制蛋白Bcl-2的表达治疗组高于模型组,差异无统计学意义(p＞0.05),凋亡促进蛋白Bax的表达治疗组低于模型组(p＜0.05),Bcl-2/Bax比值治疗组高于模型组(p＜0.05);Caspese3表达各组之间无显著差异;光镜下组织病理改变治疗组与模型组相比,无明显差异;电镜下细胞超微结构改变治疗组与模型组有一定差异。
结论:中药脉通方明显降低血糖、上调细胞凋亡抑制因子Bcl-2的表达,下调凋亡促进因子Bax的表达,上调Bcl-2/Bax的比值,从而降低或延缓细胞凋亡;改善高血糖所致组织氧化应激损伤,保护细胞超微结构及细胞的完整性,从而减轻或延缓糖尿病高糖毒性所致的组织结构病理改变,在一定程度上延缓DMED发病或者减轻其病理损伤。
Objective: To investigate the effect of Maitongfang on expression of the apoptosis protein of DMED rats' penis cavernous and the tissue ultrastructure of the DMED rats.
Methods: Sprague Dawley rats were injected intraperitoneally with streptozotocin (STZ) to make experimental models of DM. After 15-week's time, the DMED model rats were randomly divided into two groups, ie. Maitongfang group, Model control group. After 15 days' treatment, the effect of different medicines on the following parameters were detected by radioimmunoassay, biochemistry detect method, Histomorphometry, etc. which were level of blood glcose, superoxide dismutase, ratio of Bcl-2/Bax, apoptosis rate and ultrastructure of the penis cavernous.
Results: 15 days later, the level of blood glucose of Model control was higher than that of Maitongfang (p<0.05); the level of SOD of Maitongfang has no difference from Model control (p > 0.05); the ratio of Bcl-2/Bax of Maitongfang was higher than Model control (p<0.05) ; The expression of Bcl-2 Model control was higher than that of Maitongfang ( p > 0.05); The higher expression of bax between Maitongfang and Model control is the former while the expression of Caspase-3 has no difference between the two; the degree of the tissue ultrastructure pathological changes show that the Model control is heavier than that of Maitongfang.
Conclusion: Maitongfang demonstrates the action of improving the general condition, adjusting the metabolism of blood glucose, improve the activity of the expression of the apoptosis protein, protect ultrastructure of the tissue. The comprehensive curative effect of Maitongfang on DMED is remarkable.
方法:采用Sprague Dawley大鼠(SD大鼠)50只,适应性喂养1周后随机抽取10只作为正常组,其余40只采用小剂量多次腹腔注射链脲佐菌素(STZ)的方法造糖尿病大鼠模型,餐后2h血糖＞16.7mmol/l为DM成模;DM大鼠成模后正常饮食喂养15周后,每只大鼠用阿朴吗啡(APO)试验测定是否成糖尿病性勃起功能障碍(DMED)模,DMED大鼠成模后随机分组为治疗组、模型组;治疗组给以脉通方水煎液,模型组及正常组均给以等量蒸馏水,灌胃15天后断颈处死。观测一般状况、血糖、血清超氧化物歧化酶等指标以及海绵体组织细胞凋亡相关蛋白的表达,在光镜及电镜下分别观察海绵体组织超微结构的病理改变。
结果:按设计方案灌胃15后,治疗组血糖较模型组血糖降低,但仍高于正常组(p＜0.05);血清超氧化物岐化酶值治疗组与模型组差异无统计学意义(p＞0.05);凋亡抑制蛋白Bcl-2的表达治疗组高于模型组,差异无统计学意义(p＞0.05),凋亡促进蛋白Bax的表达治疗组低于模型组(p＜0.05),Bcl-2/Bax比值治疗组高于模型组(p＜0.05);Caspese3表达各组之间无显著差异;光镜下组织病理改变治疗组与模型组相比,无明显差异;电镜下细胞超微结构改变治疗组与模型组有一定差异。
结论:中药脉通方明显降低血糖、上调细胞凋亡抑制因子Bcl-2的表达,下调凋亡促进因子Bax的表达,上调Bcl-2/Bax的比值,从而降低或延缓细胞凋亡;改善高血糖所致组织氧化应激损伤,保护细胞超微结构及细胞的完整性,从而减轻或延缓糖尿病高糖毒性所致的组织结构病理改变,在一定程度上延缓DMED发病或者减轻其病理损伤。
Objective: To investigate the effect of Maitongfang on expression of the apoptosis protein of DMED rats' penis cavernous and the tissue ultrastructure of the DMED rats.
Methods: Sprague Dawley rats were injected intraperitoneally with streptozotocin (STZ) to make experimental models of DM. After 15-week's time, the DMED model rats were randomly divided into two groups, ie. Maitongfang group, Model control group. After 15 days' treatment, the effect of different medicines on the following parameters were detected by radioimmunoassay, biochemistry detect method, Histomorphometry, etc. which were level of blood glcose, superoxide dismutase, ratio of Bcl-2/Bax, apoptosis rate and ultrastructure of the penis cavernous.
Results: 15 days later, the level of blood glucose of Model control was higher than that of Maitongfang (p<0.05); the level of SOD of Maitongfang has no difference from Model control (p > 0.05); the ratio of Bcl-2/Bax of Maitongfang was higher than Model control (p<0.05) ; The expression of Bcl-2 Model control was higher than that of Maitongfang ( p > 0.05); The higher expression of bax between Maitongfang and Model control is the former while the expression of Caspase-3 has no difference between the two; the degree of the tissue ultrastructure pathological changes show that the Model control is heavier than that of Maitongfang.
Conclusion: Maitongfang demonstrates the action of improving the general condition, adjusting the metabolism of blood glucose, improve the activity of the expression of the apoptosis protein, protect ultrastructure of the tissue. The comprehensive curative effect of Maitongfang on DMED is remarkable.
引文
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[3]吴玲娟.三成ED为糖尿病所致.糖尿病新世界[J].Diabetes New Word,2007,11,18-19
[4]NIH Consencus Conference.NIH Consencus Development Panel on Conference Impotence [J].JAMA,1993;270:83
[5]Elabbady AA,Gagnon C,Hassouna MM,et ao.Diabetes mellitus increase intric Ixide synthase in penises but not in major pelvic gangnia of rats[J].BrJ Urol,1995,76:196-202
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[9]许松.糖尿病性勃起功能障碍的发病机制及治疗进展综述[J].中华男科学,2004,10(3):218-221
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[13]Hecht MJ,Neundorfer B,Kiese wetter F,etal.Neuropathy is a major contributing factor to dia-betic erectile dysfunction[J]Neurol Res,2001,23(6):651-654
[14]王为服,张元芳,丁强,徐一甄.糖尿病性阴茎勃起功能障碍大鼠模型海绵体超微结构的研究.中华泌尿外科杂志,1999,20(10):628-631
[15]Colakglu Z,Kutluary E,Ertekin C,etal.Autonomic nerve in volvement and venous leakage in diabetic men with impotence[J].BJU Int.1999.83(4):453-456
[16]柳其中,糖尿病与勃起功能障碍病因研究进展.中华男科学,2008(3):57-63
[17]Thompson CB.Apoptosis in thepathogenesis and teatment of disease[J].Scienee 1995,267(5203):1456-1462.
[18]Klein LT,Miller MI,Buttyan R,etal.Apoptosis in the rat penis after penile denervation[J].Urol,1997,158(2):626-630
[19]张新华,胡礼泉,郑新民.离断海绵体神经诱导大鼠阴茎细胞凋亡的研究[J].中华泌外科杂志2000;21:178-180
[20]DinulovicD,RadonjicG.Diabetes mellitus/male infertility[J]ArchAndrol,1990,25(3):277-293.
[21]张新华,胡礼泉.一氧化氮与雄激素在阴茎勃起中的作用[J].临床泌尿外科杂志,2000,15(4):181-183
[22]彭洪涛,刘淑萍.bcl-2基因与细胞凋亡关系的研究进展.内蒙古医学杂志[J],2006,38(4):348-351
[23]彭玮丹,张杰,惠宏襄.Bcl-2核酶与Bax在诱导食管癌细胞凋亡中的协同作用[J]中国生物化学与分子生物学学报[J],2000,16(6):827
[24]Ortiz A,Ziyadeh F N,Neilson E G.Expression of apoptosis-regulated genes on renal proximal tubular epithelial cells ex-posed to high ambient glucose and in diabetic kidneys[J].JInvest Med,1997,45:50-56
[25]刘伟,李庆军.Caspase与细胞凋亡.广东新乡医学院学报,2005,22(1),21-25,738-739
[26]Honarpour N,Du C,Richardson JA,et al.Adult Apaf-l-deficient mice exhibit male infertility [J].Dev Biol,2000,218(2):248-255
[27]Poter AG,Janicke RU,Emerging roles of,caspase-3 in apoptosis[J].Cell Death,Differ,1999,15:269-290
[28]王克文.张桂英.食管癌survivin Caspase-3表达与细胞凋亡的关系[J].现代肿瘤医学,2006,14(5):560-563
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