Page 69 - 202015

ABSTRACT OBJECTIVE： To study the improvement effects of Astragalus complanatus total flavonoids （TFA） on
adenine-induced reproductive dysfunction model male rats and its mechanism. METHODS：Male SD rats were divided into blank
group，model group，positive group（Wuzhi yanzong pill，2 g/kg），TFA high-dose，medium-dose and low-dose groups（0.05，
0.1，0.2 g/kg），with 12 rats in each group. Male rats in each group were given the corresponding drugs intragastrically at 9：00 a.m.
every day，while the model of reproductive dysfunction was reproduced by intragastric administration of adenine suspension
（except for blank group）at 3：00 p.m. on the same day，for consecutive 35 days. After medication，male rats in each group were
mated with female rats by ratio of 1 ∶ 1 in cages；7 days later，inducing-pregnancy rate of male rats were measured. ELISA assay
was used to detect the serum levels of T，E2，FSH，LH，GSH-Px，SOD，MDA，Scr and BUN in male rats；the testis，
epididymis，seminal vesicle，thymus and kidney of male rats were extracted and the organ index was calculated；HE staining was
used to observe the pathological changes of testis，epididymis and kidney；the protein expression of Bcl-2，Bax，Caspase-3 and
Caspase-9 in the renal tissue of male rats were detected by immunohistochemistry. RESULTS：Compared with blank group，the
inducing-pregnancy rate of male rats，the testis，epididymis，seminal vesicle gland，thymus indexes，the serum levels of T，E2，
SOD and GSH-Px，the protein expression levels of Bcl-2 in renal tissue were reduced significantly in model group（P＜0.01）；the
renal index，the serum levels of FSH，LH，MDA，Scr and BUN，the protein expression levels of Bax，Caspase-3 and Caspase-9
in renal tissue were increased significantly（P＜0.01）；the diameter of seminiferous tubules in testis became thinner，the spacing
was wider，and the arrangement of seminiferous cells was disordered；the wall of epididymis was thickened，the arrangement was
loose，the stroma was enlarged，the lumen was proliferated and atrophied，and the sperm in the lumen wass aggregated；in renal
tissue，interstitial fibers was proliferated，and a large number of yellow crystals were seen in renal tubules. Compared with model
group，the inducing-pregnancy rate，the testis，epididymis，seminal vesicle gland，thymus indexes，the serum levels of T，E2，
SOD and GSH-Px，the protein expression levels of Bcl-2 in renal tissue of male rats were increased significantly in the positive
group，TFA medium-dose and high-dose groups（P＜0.05 or P＜0.01），while the renal index，the serum levels of FSH，LH，
MDA，Scr and BUN，the protein expression levels of Bax，Caspase-3 and Caspase-9 in renal tissue were decreased significantly
（P＜0.05 or P＜0.01）；there was the same chage trend and most with significant difference in above indexes of TFA low-dose
group （P＜0.05 or P＜0.01）； the pathalogic changes of testis， epididymis and renal tissue were improved significantly.
CONCLUSIONS：TFA can significantly improve adenine-induced reproductive dysfunction model male rats. The mechanism may
be associated with reducing hormone FSH and LH level，the expression of apoptosis-related proteins in renal tissue，while
increasing the level of hormone T and E2 and improving oxidant stress level.
KEYWORDS Astragalus complanatus total flavonoids；Reproductive dysfunction；Horone；Oxidant stress；Mechanism；Rat

近年来，随着环境污染加剧、生活节奏加快及生育 子总黄酮（TFA）能显著升高酗酒模型小鼠睾丸、附睾指
年龄延迟，不育症患者数量急剧增加，发病率逐年上升， 数，并增加其精子数量和活力，降低精子的畸变率，这提
[1]
对人类生殖繁衍造成巨大影响 。据统计，男性不育症 示 TFA 对酗酒模型小鼠的生精功能和精子细胞损伤有
占所有不孕不育症的35％～50％，其中弱精子症是导致 一定的改善效果。本研究采用腺嘌呤灌胃雄性大鼠复
男性不育症的重要因素，其病因机制尚未完全明确，且 制生殖功能障碍模型，探讨TFA对雄性生殖障碍模型大
[2]
治疗手段与可选择的药物较少 ，因此，研发防治男性生 鼠精子质量、生育能力的影响，并通过检测大鼠血清中
殖功能障碍的新型药物是目前的热点之一。 性激素雌二醇（E2 ）、睾酮（T）、促卵泡激素（FSH）、促黄体
目前，西医在治疗弱精子症方面虽有一定成果，但 激素（LH）水平，氧化应激相关指标谷胱甘肽过氧化物
[3]
仍有部分患者的治疗效果不尽人意，尚缺乏特效药物 。 酶（GSH-Px）、超氧化物歧化酶（SOD）、丙二醛（MDA）水
中医理论认为，肾藏精而主生殖，当肾精肾气充足、精室 平，肾功能指标肌酐（Scr）、尿素氮（BUN）水平，肾组织
充盈，方能孕育生命，因此在治疗男性不育时，当先从肾 中凋亡蛋白B细胞淋巴瘤/白血病2（Bcl-2）、Bcl-2相关X
着手 [4-5] 。沙苑子为豆科植物扁茎黄芪（Astragalus com- 蛋白（Bax）、胱天蛋白酶3（Caspase-3）、Caspase-9蛋白表
planatus R. Brown.）的干燥成熟种子，性味甘、温，归肝、 达水平等指标变化，以期为治疗男性生殖功能障碍的新
肾经；具有温补肝肾、固精、缩尿、明目之功效，其肾助阳 药研发及临床应用提供参考。
之功效颇为显著；主要用于治疗肾虚腰痛、遗精早泄、遗 1 材料
[6]
尿尿频、白浊带下、眩晕、目暗昏花等 。现代药学研究 1.1 仪器
发现，其化学成分主要有黄酮类、三萜皂苷类、脂肪酸、 BS-490型全自动生化分析仪（深圳迈瑞生物医疗电
氨基酸、挥发油、甾醇类等，对血压、脑血流量、免疫功能 子股份有限公司）；H1850R 型高速冷冻离心机（湖南湘
和血液流变均有影响，且具有解热镇痛、镇静、耐寒、抗 仪实验室仪器开发有限公司）；JJ-12J 型脱水机（武汉俊
[8]
疲劳、抗炎和降脂保肝的作用 。陈勤 研究发现，沙苑 杰电子有限公司）；RM2016 型病理切片机（上海徕卡仪
[7]
中国药房 2020年第31卷第15期 China Pharmacy 2020 Vol. 31 No. 15 ·1855 ·