胰岛素联合ALT-711对糖尿病大鼠阴茎勃起功能障碍代谢记忆的影响

发布时间：2018-03-29 04:23

本文选题：糖尿病　切入点：勃起功能障碍　出处：《吉林大学》2014年硕士论文

【摘要】：目的：研究代谢记忆对于阴茎勃起功能障碍（ED）的影响及胰岛素联合ALT-711对糖尿病阴茎勃起功能相关代谢记忆的效果。方法：将50只成年（8周龄）SD大鼠随机分成5组：正常对照组（C）、糖尿病对照组（D）、胰岛素治疗组（D+I）、ALT-711治疗组（D+ALT-711）和胰岛素联合ALT-711治疗组（D+I+ALT-711）。一次性腹腔注射60mg/kg链脲霉素（streptozotocin,STZ）诱导糖尿病。诱导糖尿病8周后开始治疗，ALT-711每天腹腔注射一次（3mg/kg）。2-6个单位的中效精蛋白胰岛素一天两次皮下注射，将胰岛素治疗组与胰岛素联合ALT-711治疗组大鼠血糖控制在正常水平。连续治疗6周，通过电刺激海绵体神经测得海绵窦内压力（intracavernous pressures,ICP）评估勃起功能。测定糖基化终末产物（AGEs）及其受体（RAGE）表达、SOD活性、脂质氧化产物。另外测定阴茎海绵体平滑肌、内皮细胞及凋亡活动等组织学改变。主要指标有：ICP/MAP、阴茎海绵体内皮细胞、平滑肌细胞、nNOS、AGE及其受体RAGE表达量、MDA含量、SOD活性及凋亡指数。结果：糖尿病大鼠ICP/MAP比例、阴茎海绵体内皮细胞、平滑肌细胞显著降低，AGEs与RAGE表达显著增高。单纯胰岛素与ALT-711治疗只能使勃起功能与组织学变化部分改善。然而联合治疗组可以改善至类似于正常水平。单纯ALT-711治疗组相对于单纯胰岛素治疗组更多的减少AGEs及其受体RAGE的沉积。结论：研究表明，尽管胰岛素可以有效的控制血糖水平，但是它不能完全的改善海绵体组织的病理变化。在严格控制血糖的基础上联合AGEs交联蛋白裂解剂ALT-711可以得到更好的预期结果。联合治疗可能是通过抑制AGEs-RAGE-氧化应激轴来消除代谢记忆。
[Abstract]:Aim: to study the effect of metabolic memory on erectile dysfunction (EDD) and the effect of insulin combined with ALT-711 on diabetic penile erectile dysfunction related metabolic memory. Methods: fifty adult SD rats of 8 weeks old were randomly divided into 5 groups: normal control group, diabetes control group, insulin treatment group, insulin treatment group and insulin combined with ALT-711 treatment group. 60mg/kg chain was injected intraperitoneally once. Diabetes induced by streptozotocinn (STZ). After 8 weeks of diabetes induction, the treatment of ALT-711 was started by intraperitoneal injection of 3 mg / kg 路kg. 2-6 units of midacting protamine insulin twice a day twice a day. The blood glucose of rats in insulin treatment group and insulin combined with ALT-711 group was controlled to normal level. The pressure in cavernous sinus was measured by electrical stimulation of cavernous nerve (ICP) to evaluate erectile function. The expression of superoxide dismutase (SOD) and lipid oxidation products were measured by glycation end product (ages) and its receptor (rage). The smooth muscle of cavernous body of penis was also measured. The main outcome measures were as follows: 1 ICP / MAPP, the expression of RAGE in cavernous endothelial cells and smooth muscle cells, the content of RAGE, the activity of SOD and the index of apoptosis. Results: the ratio of ICP/MAP and the endothelial cells of cavernosum of penis in diabetic rats, Smooth muscle cells decreased the expression of ages and RAGE significantly. Insulin and ALT-711 treatment only partially improved erectile function and histological changes. However, the combined treatment group could be improved to similar to the normal level. In the treatment group, the deposition of AGEs and its receptor RAGE was more reduced than that in the insulin alone group. Conclusion: studies have shown that, although insulin can effectively control blood glucose levels, However, it can not completely improve the pathological changes of cavernous tissue. The combination of AGEs crosslinking protein lysant ALT-711 on the basis of strict blood glucose control can achieve better expected results. The combined therapy may be by inhibiting the AGEs-RAGE-oxidation response. Excites the axis to eliminate metabolic memory.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R587.2;R698

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