Gossypol ameliorates liver fibrosis in diabetic rats induced by high-fat diet and streptozocin

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• 作者：Guorong Chen^a ; Rongrong Wang^b ; Hanbin Chen^b ; Liang Wu^b ; Ren-Shan Ge^c ; Yili Wang^a ; ^{wangyili@mail.xjtu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：11β-HSD1 ; 11β-hydroxysteroid dehydrogenase 1 ; 11β-HSD2 ; 11β-hydroxysteroid dehydrogenase 2 ; ALT ; alanine aminotransferase ; Cat ; catalase ; Colla1 ; collagen ; Col3a1 ; collagen III ; Fn1 ; fibronectin 1 ; FN ; fibronectin ; G6pc ; glucose-6-phosphatase ; Gpx1 ; glutathione peroxidase 1 ; Gsta ; glutathione S-transferase ; HE ; hematoxylin-eosin ; LDL ; low density lipoprotein ; Nr3c1 ; glucocorticoid receptor ; Pck1 ; phosphoenolpyruvate carboxykinase ; Rps16 ; ribosome protein S16 ; α-SMA ; α-smooth muscle actin ; STZ ; s
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：149
• 期：Complete
• 页码：58-64
• 全文大小：1861 K

文摘

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitors have been shown to treat type 2 diabetes (T2D). Since gossypol is an 11β-HSD1 inhibitor, the objective of the present study was to treat T2D and T2D-related liver fibrosis in rat model using low-dose gossypol. T2D was induced by feeding with high fat diet plus injection of streptozocin (30 mg/kg). Diabetic rats were treated with either vehicle control or racemic gossypol with a dose of 15 mg/kg/day for 4 weeks followed by 15 mg/kg/week for additional 8 weeks. Blood glucose, cholesterol, LDL, and triglycerides were measured. Messenger mRNA levels of glucocorticoid receptor (Nr3c1), phosphoenolpyruvate carboxykinase (Pck1), glucose-6-phosphatase (G6pc), collagen I (Col1a1), collagen III (Col3a1), fibronectin (Fn1), tissue inhibitor of metalloproteinase 1 (Timp1), and 2 (Timp2) were measured. T2D rats had higher serum glucose, cholesterol, LDL, and triglyceride levels compared to control. Liver Nr3c1, Col1a1, Col3a1, Fn1, Timp1, and Timp2 were increased in T2D rats. T2D liver showed significant fibrosis with the increases of α-smooth muscle actin and fibronectin. After gossypol treatment, serum glucose level was lowered by 64%. Liver fibrosis was significantly ameliorated. Nr3c1, Col1a1, Col3a1, Fn1, Timp1, Timp2, Pck1 as well as G6pc levels were significantly reduced. In conclusion, low dose gossypol is effective for the treatment of T2D and T2D-related fibrosis.