目的 研究无比山药丸对“房事不节＋劳倦过度”导致的肾阳虚模型小鼠勃起功能障碍的作用及作用机制。方法 选取性功能良好的雄性ICR小鼠60只，随机分为对照组、模型组、金匮肾气丸（1.7 g/kg）组和无比山药丸低、中、高剂量（0.75、1.50、3.00 g/kg）组。采用强迫小鼠游泳致力竭的方法造成劳倦过度，并以Colldege效应诱导雄性小鼠房事不节，建立肾阳虚勃起功能障碍模型小鼠。造模同时ig相应药物，连续8周。测定小鼠肛温、抓力、自主活动次数、尾部微循环血流量及性行为等肾阳虚证候指标；检测血清中尿酸（uric acid，UA）、肌酐（creatinine，CR）和尿素氮（blood urea nitrogen，BUN）水平；检测肾脏组织中丙二醛（malonaldehyde，MDA）水平和超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathion peroxidase，GSH-PX）活性；采用苏木素-伊红（HE）染色观察肾组织病理变化；采用TUNEL染色观察肾组织细胞凋亡情况；采用试剂盒检测阴茎组织中鸟苷酸环化酶（guanylate cyclase，GC）、一氧化氮合酶（nitric oxide synthase，NOS）活性和一氧化氮（nitric oxide，NO）、环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）水平；采用Western blotting检测阴茎组织中内皮型一氧化氮合酶（endothelial nitric oxide synthase，eNOS）和GC蛋白表达。结果 无比山药丸显著增加肾阳虚模型小鼠的肛温、抓力、自主活动次数、尾部微循环血流量及捕捉、骑跨次数（P＜0.05、0.01），显著缩短捕捉、骑跨潜伏期（P＜0.01）；降低血清中UA、CR、BUN水平（P＜0.05、0.01）；降低肾脏组织MDA水平（P＜0.01），升高SOD和GSH-PX活性（P＜0.05、0.01）；改善肾脏病变及细胞凋亡情况；增加阴茎组织NO、cGMP水平和NOS及GC活性（P＜0.01）；上调阴茎组织eNOS、GC蛋白表达（P＜0.01）。结论 无比山药丸能够改善“房事不节＋劳倦过度”致肾阳虚证候，调节勃起功能障碍，其作用机制可能与UA介导的NO-cGMP途径有关。

Objective To observe the effect and mechanism of Wubi Shanyao Pills (无比山药丸) on erectile function of kidney-yang deficiency model mice caused by sexual overstrain and over-exertion. Methods Sixty male ICR mice with good sexual function were randomly divided into control group, model group, Jinkui Shenqi Pills (1.7 g/kg) group and Wubi Shanyao Pills low-, medium- and high-dose (0.75, 1.50, 3.00 g/kg) groups. The over-exertion model was caused by forcing mice to swim to exhaustion, and model of erectile dysfunction due to kidney-yang deficiency was established by sexual overstrain in male mice with College effect. Mice were ig corresponding drugs for 8 consecutive weeks at the same time as modeling. The anal temperature, grasping power, number of autonomous activity, blood flow in tail microcirculation and sexual behavior of mice with kidney-yang deficiency symptoms were measured; Uric acid (UA), creatinine (CR) and blood urea nitrogen (BUN) levels in serum were detected; Malondialdehyde (MDA) level and superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) activities in kidney tissue were detected; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe the apoptosis of renal tissue; Kits were used to detect guanylate cyclase (GC), nitric oxide synthase (NOS) activities and nitric oxide (NO), cyclic guanosine monophosphate (cGMP) levels in penile tissue. Western blotting was used to detect protein expressions of endothelial nitric oxide synthase (eNOS) and GC in penis tissue. Results Wubi Shanyao Pills significantly increased the anal temperature, grasping power, number of autonomous activities, microcirculation blood flow in tail, capture and straddle times (P < 0.05, 0.01), and reduced capture and straddle latency (P < 0.01), decreased UA, CR, and BUN levels in serum (P < 0.05, 0.01), decreased MDA level in kidney tissue (P < 0.01), increased SOD and GSH-PX activities in kidney tissue (P < 0.05, 0.01), improved kidney lesions and cell apoptosis, increased NO, cGMP levels and NOS, GC activities in penile tissue (P < 0.01), and up-regulated eNOS and GC protein expressions in penile tissue (P < 0.01). Conclusion Wubi Shanyao Pills can improve the syndrome of kidney-yang deficiency caused by sexual overstrain and over-exertion, regulate erectile dysfunction, and its mechanism may be related to UA-mediated NO-cGMP pathway.

R285.5

国家自然科学基金资助项目（81873036）；浙江省重点研发计划项目（2017C03052）；浙江省重点实验室项目（2012E10002）