Background and Objective:
This study investigated whether rapamycin has a protective
effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative
stress.
Methods:
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.
Results:
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).
Conclusion:
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.
Translational Induction of the Inhibitor of Apoptosis Protein HIAP2 during Endoplasmic Reticulum Stress Attenuates Cell Death and Is Mediated via an Inducible Internal Ribosome Entry Site Element
