探讨转化生长因子β1、内皮型一氧化氮合酶在糖尿病性大鼠海绵体血管结构重构中的作用

Expression and activity of transforming growth factor-β1, endothelial nitric oxide synthase in cavernous vascular structural remodeling of diabetic rats

目的探讨转化生长因子B1（transforming growth factor-β1，TGF-β1）、内皮型一氧化氮合酶（endothelial nitric oxide syntbase，eNOS）在糖尿病（diabetesmellitus，DM）性大鼠海绵体血管结构重构中的表达及其活性研究。方法52只成年雄性SI）大鼠，按随机数字分类法分配到4个DM组、4个对照组（NDM）。在4个DM组注射链脲佐菌素4d制造DM动物模型，造模成功后于第2、4、8、16周取大鼠阴茎处组织，免疫组化Envision法染色观察DM组和NDM组大鼠阴茎海绵体组织。用免疫组化定性及半定量检测TGF-β1、eNOS蛋白的表达。结果16周时，大鼠DM组血清中HbAlc值较NDM组有明显上调（P〈0．01）；注射APO后可观测到大鼠DM组较NDM组其阴茎勃起率及阴茎勃起次数明显减低（P〈0．01）；大鼠DM组eNOS值较NDM组明显下调（P〈0．01）。8周时，大鼠DM组较NDM组其阴茎海绵体局部TGF．B1表达水平明显升高（P〈0．01），检测结果时间曲线具有上升趋势。DM组大鼠阴茎海绵体组织中TGF-β1蛋白与周龄呈正相关性（r=0．947，P〈0．01）；DM组大鼠阴茎海绵体组织eNOS与周龄呈负相关（r=-0．945，P〈0．01）。此外，TGF-β1与eNOS在不同周龄的表达呈负相关（r=-0．891，P〈0．01）。结论在控制血糖的前提下，采取干预措施影响TGF-β1的表达或拮抗其功能，有可能是治疗勃起功能障碍（erectile dysfunction，ED）的新途径。

Objective To investigate the expression and activity of transforming growth factor-β1 （TGF- β1 ）and endothelial nitric oxide synthase（ eNOS）in the cavernous vascular structural remodeling of diabetic rats. Methods 52 adult male SD rats were randomly assigned to experimental group（DM） and control group（NDM）. In DM group, diabetes was induced in rats 4 days after intraperitoneal injection with streptozotoein. HbAle was measured on 2, 4, 8, and 16 weeks after injection. Penile tissues were harvested. The protein expression of TGFβ1 and eNOS in situ was evaluated by the Envision immunohistochemistry. Results Compared to NDM group, the expression of the HbAlc increased significantly in DM group on the 16th week（P 〈0. 01 ）, both the penile erection rate and penile erectile times decreased significantly in DM group on the 16th week（ P 〈 0. 01 ）, and the value of eNOS decreased on the 16th week（P 〈0. 01 ）. The expression of TGF-β1 went up in DM group compared to NDM group on the 8th week（P 〈 0. 01 ） and sustained to the 16th week（P 〉 0. 05 ）. In DM group, we found that TGF-β1 protein in cavernous body of penis was positively related with age in weeks（r =0. 947, P 〈0. 01 ） ; and eNOS in cavernous body of penis was negatively related with age in weeks （r = -0. 945, P 〈 0. 01 ）. Meanwhile, the expression of TGF-β was negatively related with the eNOS （r = -0. 891, P 〈 0. 01 ）. Conclusion Our results indicate that TGF-β1 plays an important role in the pathogenesis of diabetic erectile dysfunction（ED） and TGF-β1 inhibition may be a promising strategy to prevent development of diabetic ED.