三七总皂苷的抗凋亡作用对糖尿病性勃起功能障碍大鼠勃起功能的影响

Antiapoptotic effects of Panax notoginseng saponins on erectile function in diabetic rats with erectile dysfunction

摘要:

目的：通过观察三七总皂苷（Panax notoginseng saponins，PNS）对糖尿病性（diabetes mellitus，DM）勃起功能障碍（erectile dysfunction，ED）大鼠的阴茎细胞凋亡及Bax和Bcl-2表达的影响，探讨PNS改善DMED大鼠勃起功能的可能性及其作用途径。方法：建立DMED大鼠模型，随机分成PNS50、PNS100、PNS150处理组和DMED组，前3组DMED大鼠每日腹腔注射PNS剂量分别为50、100、150 mg/kg，DMED组（未注射PNS）和正常对照组（正常大鼠）腹腔注射等剂量生理盐水。4周后，电刺激阴茎海绵体神经测定阴茎海绵体内压（intracavernosal pressure，ICP）与平均动脉压（mean arterial pressure，MAP）比值；免疫组化测阴茎组织中Bax和Bcl-2蛋白表达；TUNEL法检测阴茎组织细胞凋亡率；电镜观察阴茎组织细胞凋亡情况。结果：实验结束时，PNS100、PNS150处理组与DMED组相比，体质量明显增高，血糖水平降低；ICP和ICP/MAP均有明显升高，Bcl-2升高而Bax的表达和细胞凋亡率下降（P<0.05）。电镜观察发现：PNS50处理组海绵体血管内皮细胞胞核肿胀，血管内皮细胞断裂。DMED组血管内皮粗糙断裂，平滑肌细胞凋亡，血栓形成。PNS100、PNS150处理组和正常对照组，未发现以上改变。结论：PNS通过上调Bcl-2/Bax的比值，减少阴茎组织血管内皮细胞和平滑肌细胞的凋亡，保护细胞功能，提高DMED大鼠的勃起功能。

Abstract:

Objective：To detect whether Panax notoginseng saponins（PNS） could improve the erectile function of diabetic mellitus （DM） rats with erectile dysfunction（ED），to find the possible ways by which PNS worked and to explone effects of PNS on Bax and Bcl-2 expressions. Methods：Model of DMED was established and the rats were randomly divided into four groups：PNS treated group（intraperitoneal injection with doses of 50 mg/（kg·d），100 mg/（kg·d），150 mg/（kg·d）） and DMED group（intraperitoneal in－jection with saline）；at the same time，normal rats injected with saline were taken as controls（normal control group）. Four weeks later，ratio of intracavernous pressure（ICP） and mean arterial blood pressure（MAP） was measured by electro-stimulating of cavernous nerve. Then cavernous bodies of penis of all experimental rats were harvested and their expressions of Bcl-2 and Bax were determined by immunohistochemistry. Apoptosis of penile tissue cell was detected by TUNEL. Changes of the cavernous bodies in ultrastructures were observed by electron microscopy. Results：ICP/MAP was elevated and value of Bcl-2/Bax was increased in middle and high dose group than in DMED group. Results of electron microscopy uncovered that there were ruptured endothelium and impaired smooth muscle cells in the low dose PNS group and DMED group and even thrombosis in DMED group；in the middle，high dose group and normal control group，there were no abnormal changes. Conclusions：PNS might elevate the value of Bcl-2/Bax to protect endothelium and smooth muscle cells from apoptosis as well as protect the function of penis cells，thereby to improve erectile function.