Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43  

作　　者：MingXU Chen HU Hussein-hamed KHAN T Fang.hong SHI Xiao-dong CONG Qing LI Yin DAI De-zai DAI 

机构地区：[1]Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China [2]Department of Pharmacy, Renji Hospi- tal, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China [3]Zhejiang University of Traditional Medicine, Hangzhou 311401, China [4]Department of Pharmacology, University of Adam, Yemen

出　　处：《Acta Pharmacologica Sinica》2016年第2期246-254,共9页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China （No 81570413 and 81070145）.

摘　　要：Aim： Argirein （rhein-arginine） is a derivative of rhein isolated from Chinese rhubarb （Rheum Officinale Baill） that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced （hypergonadotrophic） and diabetic （hypogonadotrophic） hypogonadism in male rats. Methods： Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol （ISO） or streptozotocin （STZ）. ISO-injected rats were treated with argirein （30 mg.k-1.d-1, po） or testosterone replacement （0.5 mg.kg-1-d-1, sc） for 5 days, and STZ-injected rats were treated with argirein （40-120 mg.kg-1.d-1, po） or aminoguanidine （100 mg.kg-1-d-1, po） for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A （ETA）, connexin 43 （Cx43） and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO （1 pmol/L） or high glucose （27 mmol/L）. Results： ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum, in the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCs was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein （0.3-3 pmol/L） exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Conclusion�Aim： Argirein （rhein-arginine） is a derivative of rhein isolated from Chinese rhubarb （Rheum Officinale Baill） that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced （hypergonadotrophic） and diabetic （hypogonadotrophic） hypogonadism in male rats. Methods： Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol （ISO） or streptozotocin （STZ）. ISO-injected rats were treated with argirein （30 mg.k-1.d-1, po） or testosterone replacement （0.5 mg.kg-1-d-1, sc） for 5 days, and STZ-injected rats were treated with argirein （40-120 mg.kg-1.d-1, po） or aminoguanidine （100 mg.kg-1-d-1, po） for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A （ETA）, connexin 43 （Cx43） and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO （1 pmol/L） or high glucose （27 mmol/L）. Results： ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum, in the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCs was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein （0.3-3 pmol/L） exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Conclusion�

关 键 词：argirein RHEIN male hypogonadism hypergonadotrophic hypogonadotrophic ETA connexin 43 AMINOGUANIDINE TESTOSTERONE 

分 类 号：R9[医药卫生—药学]