沙苑子提取物对糖尿病所导致睾丸损伤的治疗作用  

Therapeutic effect of Semen Astragall Complanati extract on diabetes-induced testicular injury

作　　者：李佳琪 莫廷美 王小轩 林娜 韦景薰 闫炳荣 傅杨恺 黄鹭铭 马博[1] LI Jiaqi;MO Tingmei;WANG Xiaoxuan;LIN Na;WEI Jingxun;YAN Bingrong;FU Yangkai;HUANG Luming;MA Bo(School of Pharmaceutical Sciences,Nanjing Tech University,Nanjing 211800,China;Jiangsu Provincial Institute of Materia Medica Co.,Ltd.,Nanjing 211800,China)

机构地区：[1]南京工业大学药学院,江苏南京211800 [2]江苏省药物研究所有限公司,江苏南京211800

出　　处：《生物加工过程》2025年第2期199-206,共8页Chinese Journal of Bioprocess Engineering

基　　金：江苏省高等学校基础科学(自然科学)面上项目(21KJB350020);江苏省先进生物制造创新中心重点项目(XTC2203);南京市科技局生命健康科技专项(202110015);江苏省大学生创新创业训练计划重点项目(202110291056Z)。

摘　　要：研究沙苑子(SAC)提取物对糖尿病所致睾丸损伤的保护作用及分子机制。通过高脂饲料喂养结合腹腔注射链脲佐菌素(STZ),建立2型糖尿病小鼠模型。将雄性ICR小鼠随机分为正常组,模型组,低剂量SAC组(100 mg/kg)、中剂量SAC组(200 mg/kg)和高剂量SAC组(400 mg/kg)。建模成功后,持续治疗8周。检测小鼠血糖浓度、睾丸指数、精子计数及形态以及睾丸组织内丙二醛(MDA)、H 2 O 2及过氧化氢酶(CAT)水平;并通过组织形态学分析观察睾丸组织;免疫组织化学检测8羟基脱氧鸟苷(8 OHdG),4羟基壬烯醛(4 HNE)和NADPH氧化酶4(Nox4)在睾丸中的表达;实时荧光定量聚合酶链式反应(RT qPCR)检测Nox4 mRNA水平;Western blotting检测Nox4在睾丸中的表达。结果表明,与模型组相比,低、中和高剂量SAC组均有一定的降糖作用,且能在一定程度上恢复睾丸形态,提高睾丸指数和精子计数,并且可以显著降低睾丸组织内的MDA和H 2 O 2水平,明显提升CAT水平;组织病理学和免疫组化的结果显示,SAC提取物能够在一定程度上改善睾丸病理形态和糖尿病所引起的氧化应激损伤;除此之外,SAC提取物能显著抑制糖尿病所导致的Nox4 mRNA和蛋白的异常表达。由此可知,SAC提取物通过抑制Nox4和氧化应激反应,以发挥对糖尿病所致睾丸损伤的保护作用。Semen Astragall Complanati(SAC)extract was studied with regards to its protective effect and mechanism on diabetes-induced testicular injury.The type 2 diabetic mouse model was established by feeding with high-fat diet and intraperitoneal injection of streptozotocin(STZ).Male ICR mice were randomly divided into normal group,model group and three SAC groups(100,200 and 400 mg/kg SAC),respectively.The mice in SAC groups were administrated intragastrically for 8 weeks,while those in the normal and model groups were dosed with normal saline.At the end of treatment,the blood glucose levels,testis index,sperm count and morphology were detected,and the biochemical indicators including malondialdehyde(MDA),H 2 O 2,catalase(CAT)were measured by Biochemical kit assay.The testis tissue slices were subsequently analyzed using HE staining experiments,and the contents of 8-OHdG and 4-HNE were detected by immunohistochemistry.To further explore the mechanism of action,Nox4 mRNA and protein level were detected by RT-qPCR and Western blotting assay,respectively.Compared with the model group,SAC treatment helped the recovery from diabetic testicular injury based on histological pathology,with significant improvement for testicular index and sperm quality.Moreover,SAC could not only significantly attenuate the MDA and H 2 O 2 contents but also enhance CAT activities in the testis tissue.Based on the immunohistochemical studies using 8-OHdG and 4-HNE assay,the SAC extract could inhibit oxidative stress damage caused by diabetes to a certain extent.In addition,SAC could inhibit the abnormally elevated protein expression and the Nox4 level in testis tissue.Overall,our research suggests that SAC extract is a potential therapeutic agent in the treatment of diabetes-induced testicular injury through the modulation of Nox4 level and oxidative stress.

关 键 词：沙苑子提取物 糖尿病 NOX4 睾丸损伤 氧化应激 

分 类 号：R965[医药卫生—药理学]