来曲唑对环磷酰胺损伤大鼠生精功能的影响及作用机制初探  

Effect of letrozole on spermatogenic function of cyclophosphamide injured rats and its mechanism

作　　者：王澍弘[1] 王顺德[1] 李晶[2] 李行[1] 李美材 龙腾博 李晓霞[1] WANG Shu-hong;WANG Shun-de;LI Jing(Department of Andrology,Chongqing Three Gorges Central Hospital,Chongqing 404000,China;Central Laboratory,Chongqing Three Gorges Central Hospital,Chongqing 404000,China)

机构地区：[1]重庆三峡中心医院男性科,重庆404000 [2]重庆三峡中心医院中心实验室,重庆404000

出　　处：《临床和实验医学杂志》2019年第22期2377-2381,共5页Journal of Clinical and Experimental Medicine

基　　金：重庆市卫生计生委面上项目(编号:2016MSXM114)

摘　　要：目的观察来曲唑(LE)对环磷酰胺(CXP)损伤大鼠生精功能的影响及作对早幼粒细胞白血病锌指蛋白(PLZF)和跨膜酪氨酸激酶受体(C-kit)的影响。方法将15只清洁级成年雄性SD大鼠随机分为三组,每组5只。模型组:依据采用CXP 35 mg/kg给予腹腔注射5 d,自第6天起灌胃淀粉12.5μg/d,连续30 d。空白对照组:用生理盐水代替CXP等量腹腔注射5 d,从第6天起灌胃淀粉12.5μg/d,连续30 d。实验组:用CXP 35 mg/kg给予腹腔注射5 d,自第6天起灌胃来曲唑12.5μg/d,连续30 d。观察各组大鼠体重、睾丸指数、附睾指数;HE染色观察睾丸病理学变化,比较生精小管直径(MSTD)和睾丸活检评分(TBS);TUNEL凋亡染色检测生殖细胞凋亡情况;Western blot检测睾丸组织中PLZF、C-kit的表达。结果与空白对照组相比,模型组睾丸指数和血清T显著降低,而FSH和LH显著升高,差异具有统计学意义(P<0.05);与模型组相比,实验组附睾指数和血清T显著升高,而大鼠体重、FSH和LH显著降低,差异具有统计学意义(P<0.05);HE结果显示模型组大鼠睾丸曲细精管管腔显著缩窄,管腔空隙变大,生精细胞紊乱,数量减少,发育迟缓,未见精子细胞,且管腔中央无絮状精子形成,而正常对照组和实验组可见大量精子细胞和絮状精子,且各层生精细胞排列整齐;TUNEL法检测结果显示模型组有大量生殖细胞出现凋亡,而空白对照组和实验仅有少量生殖细胞凋亡。与空白对照组比较,模型组和实验组MSTD显著降低(P<0.05),与模型组比较,实验组MSTD显著升高(P<0.05)。与空白对照组比较,模型组TBS显著下降(P<0.05),与模型组比较,实验组TBS显著升高(P<0.05);而空白对照组和实验组无统计学意义(P>0.05)。模型组睾丸组织中PLZF和C-kit的表达水平显著低于空白对照组和实验组(P<0.05)。而空白对照组和实验组中PLZF和C-kit水平无统计学意义(P>0.05)。结论LE对环磷酰胺损伤的大鼠生精功能具有显著Objective To observe the effect of letrozole(LE)on spermatogenic function of cyclophosphamide(CXP)injured rats and its effects on zinc-finger protein(PLZF)and transmembrane tyrosine kinase receptor(c-kit)in promyelocytic leukemia.Methods 15 adult male SD rats with detergent were divided into three groups,with 5 rats in each group.In the model group,intraperitoneal injection was given at CXP 35 mg/kg for 5 days,followed by intragastric starch 12.5 mg/day for 30 consecutive days from the 6th day.In the blank control group,normal saline was used instead of CP for the same amount of intraperitoneal injection for 5 days.In the experimental group,CXP 35 mg/kg was injected intraperitoneally for 5 days,followed by gastric lavage at 12.5 mg/d for 30 days starting from the 6th day.Body weight,testicular index and epididymis index were observed in each group.HE staining was used to observe the pathological changes of testis,and the diameter of spermatogenic tubule(MSTD)and testicular biopsy score(TBS)were compared.Apoptosis was detected by TUNEL apoptosis staining.The expression of PLZF and c-kit in testicular tissue was detected by Western blot.Results Compared with the blank control group,the testis index and serum T in the model group were significantly decreased,while FSH and LH were significantly increased,the difference was statistically significant(P<0.05).Compared with the model group,the epididymal index and serum T in the experimental group were significantly increased,while the body weight,FSH and LH in the rats were significantly decreased,with statistically significant difference(P<0.05).HE results showed that the testis seminiferous tubules in the model group were significantly narrowed,the gap in the testis seminiferous tubules was enlarged,the spermatogenic cells were disordered,the number of spermatogenic cells was reduced,the development was delayed,no spermatocytes were found,and no flocculent spermatogenesis was found in the center of the testis seminiferous tubules,while a large number of spermatogenic

关 键 词：大鼠 环磷酰胺 来曲唑 生精功能 早幼粒细胞白血病锌指蛋白 跨膜酪氨酸激酶受体 

分 类 号：R698.2[医药卫生—泌尿科学] R-332[医药卫生—外科学]