Shi Wenjiao, Guo Zhixin, Yuan Ruixia
Department of Endocrinology, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Department of Endocrinology, Second Hospital, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
Endocr Metab Immune Disord Drug Targets. 2019;19(5):665-675. doi: 10.2174/1871530319666190102112844.
This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress.
Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR.
There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05).
Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.
本研究探讨雷帕霉素是否通过调节自噬、内质网应激和氧化应激对糖尿病大鼠睾丸产生保护作用。
将30只雄性Sprague-Dawley大鼠随机分为三组：对照组、糖尿病组和雷帕霉素治疗糖尿病组，糖尿病诱导成功后，雷帕霉素治疗糖尿病组大鼠接受雷帕霉素灌胃（2mg·kg-1·d-1）。通过腹腔注射链脲佐菌素（STZ，65mg·kg-1）诱导糖尿病大鼠。雷帕霉素治疗8周后处死所有大鼠。采用苏木精-伊红染色观察睾丸病理变化。通过蛋白质印迹法或实时荧光定量PCR检测自噬相关蛋白（Beclin1、微管相关蛋白轻链3（LC3）、p62）、内质网应激标记蛋白（CCAAT/增强子结合蛋白（C/EBP）同源蛋白（CHOP）、半胱天冬酶-12）、氧化应激相关蛋白（p22phox、核因子红细胞2相关因子2（Nrf2））和凋亡相关蛋白（Bax、B细胞淋巴瘤-2（Bcl-2））的蛋白或mRNA表达。
糖尿病大鼠睾丸出现明显病理变化。糖尿病大鼠睾丸中Beclin1、LC3、Nrf2、Bcl-2的表达显著降低，p62、CHOP、半胱天冬酶12、p22phox和Bax显著升高（P<0.05）。然而，雷帕霉素治疗8周显著逆转了糖尿病大鼠睾丸的上述变化（P<0.05）。
雷帕霉素似乎通过诱导自噬表达并抑制内质网应激、氧化应激和凋亡表达，对糖尿病大鼠睾丸产生保护作用。
