摘要
目的 探讨毛蕊花糖苷对腺嘌呤诱导的不育症大鼠的作用及其机制。方法 大鼠随机分为空白组、模型组、阳性对照组(100 mg/kg复方玄驹胶囊)和毛蕊花糖苷低、高剂量组(50、100 mg/kg)。除空白组外,其余各组每天灌胃150 mg/kg腺嘌呤,连续14 d,建立不育症大鼠模型。造模结束后,各组灌胃给予相应剂量药物,连续给药28 d。观察各组大鼠一般活动情况,计算脏器(肝脏、肾脏、睾丸、附睾)指数,于显微镜下观察精子情况,HE染色观察大鼠肝脏、肾脏及睾丸组织病理形态,并进行精子发生评估(Johnsen评分法),ELISA法检测血清T、LH、FSH、GnRH水平,RT-qPCR和Western blot法检测大鼠睾丸组织mTOR、LC3B、ULK1 mRNA和蛋白表达。结果 与空白组比较,模型组大鼠肾脏指数升高(P<0.05),精子计数、精子活动率及精子指数降低(P<0.05),血清T、GnRH水平降低(P<0.05),LH、FSH水平升高(P<0.05),肾脏和睾丸组织病理损伤明显,睾丸组织mTOR mRNA和蛋白表达升高(P<0.05),LC3B、ULK1 mRNA和蛋白表达降低(P<0.05),p-mTOR蛋白表达降低(P<0.05);与模型组比较,毛蕊花糖苷高剂量组肾脏指数降低(P<0.05),精子计数、精子活动率升高(P<0.05),血清T水平升高(P<0.05),LH、FSH水平降低(P<0.05),肾脏和睾丸组织病理损伤有不同程度改善,睾丸组织mTOR mRNA和蛋白表达降低(P<0.05),LC3B、ULK1 mRNA和蛋白表达升高(P<0.05),p-mTOR蛋白表达升高(P<0.05),且毛蕊花糖苷高剂量作用与阳性对照药复方玄驹胶囊相当。结论 毛蕊花糖苷能有效提高不育症大鼠的精子质量,改善性激素紊乱、生殖功能及肾脏、睾丸组织病理性损伤,其作用机制可能与增强正性调控自噬,调节下丘脑-垂体-睾丸轴紊乱有关。
AIM To explore the effects and mechanism of verbascoside on adenine-induced infertility in rats.METHODS Rats randomly divided into the blank group,the model group,the positive control group(100 mg/kg Compound Xuanju Capsule)and low and high dose groups of verbascoside(50 and 100 mg/kg)were given 150 mg/kg adenine daily for 14 days to establish the rat model of infertility,except those of the blank group,followed by the 28 days corresponding gavage of the drugs.The rats had their general activities observed;their indexes levels of liver,kidney,testis and epididymis calculated;their sperms checked under the microscope;their pathological morphology of the liver,the kidney and the testis observed by HE staining;their spermatogenesis evaluated using the Johnsen scoring method;their serum levels of T,LH,FSH and GnRH detected by ELISA;and their testicular mRNA and protein expressions of mTOR,LC3B and ULK1 detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group displayed increased index level of the kidney(P<0.05),decreased sperm count,sperm activity rate and sperm index level(P<0.05),decreased serum levels of T and GnRH(P<0.05),increased levels of LH and FSH(P<0.05),obviously pathological damage of the kidney and testis,increased testicular expressions of mTOR mRNA and protein(P<0.05),decreased expressions of LC3B and ULK1 mRNA and protein(P<0.05),and decreased expression of p-mTOR protein(P<0.05).Compared with the model group,the high-dose verbascoside group demonstrated decreased renal index level(P<0.05),increased sperm count and sperm activity rate(P<0.05),increased serum T level(P<0.05),decreased LH and FSH levels(P<0.05),improved pathological damage of the kidney and the testis at different levels,decreased testicular expressions of mTOR mRNA and protein(P<0.05),increased expressions of LC3B,ULK1 mRNA and protein(P<0.05),and increased expression of p-mTOR protein(P<0.05).The high-dose verbascoside group displayed the same effects as those of the positive control Compound Xuanju Capsule.CONCLUSION Verbascoside can effectively improve the sperm quality,sex hormone disorder,reproductive function and pathological damage of kidney and testis in infertile rats,and its mechanism may be related to the enhanced positive regulation of autophagy and regulated hypothalamus-pituitary-testis axis disorder.
作者
王志
侯强
冉峥
杨建华
WANG Zhi;HOU Qiang;RAN Zheng;YANG Jian-hua(State Key Laboratory of Pathogenesis,Prevention and Treatment of Central Asian High Incidence Diseases,Department of Pharmacy,The First Hospital Affiliated to Xinjiang Medical University,Urumqi 830054,China;College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China)
出处
《中成药》
CAS
CSCD
北大核心
2024年第3期771-779,共9页
Chinese Traditional Patent Medicine
基金
国家自然科学基金资助项目(82160772)
新疆维吾尔自治区自然科学基金资助项目(2022D01C260)
省部共建中亚高发病成因与防治国家重点实验室面上项目(SKL-HIDCA-2021-9)。
