The effects of gossypol on expressions of transforming growth factor-β1, fibronectin and 11β-hydroxysteroid dehydrogenase in nephridial tissue in rats with diabetes mellitus

Objective To observe the effects of gossypol on expressions of transforming growth factor-β1 (TGF-β1), fibronectin (FN) and 11β-hydroxysteroid dehydrogenase (11β-HSD) in nephridial tissue in rats with diabetes mellitus. Methods Thirty male Sprague-Dawley rats were randomly divided into three groups: normal control, type 2 diabetes and gossypol treatment group . After high-fat feeding for 4 weeks, the later two groups were injected with low dosage strepozotocin (30 mg/kg) intraperitoneally to induce type 2 diabetic rat model. The rats in gossypol treated group were given gossypol at the dosage of 15 mg/kg once per day for 4 weeks by gavage. And since the 5th week, the times of gavages had been changed into once per week at the same dosage and lasted to the 12th week . The levels of blood glucose, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) were measured. Additionally, the morphological changes of the kidney were studied by light microscopy and transmission electron microscopy respectively. The mRNA expressions of TGF-β1, FN, 11β-HSD and 11β-HSD2 in nephridial tissue were assayed by semi-quantity RT-PCR. The protein expressions of TGF-β1 and FN in nephridial tissue were determined by immunohistochemistry. Results The blood levels of glucose, TC and LDL- c were increased significantly in type 2 diabetic group compared with normal control group(P<0. 01). The volume of glomerulus and the deposition of PAS positive substance in the glomerular interstitium were increased under light microscopy, and the glomerular basal membrane was thicker in type 2 diabetic group than those in normal control group under transmission electron microscopy. The mRNA and protein expressions of TGF-β1 and FN were increased(P<0. 01), and the mRNA expression of 11β-HSD2 was decreased(P<0. 05), while the mRNA expression of 11β-HSD1 was unchanged in type 2 diabetic group compared with normal control group. After the treatment of gossypol, the level of the blood glucose was significantly decreased(P< 0. 01), and the levels of TC, LDL-c showed a trend of decrease but had no statistical differences compared with type 2 diabetic group. The morphology of nephridial tissue was ameliorated in gossypol treatment group. The mRNA and protein expressions of TGF-β1 and FN were decreased(0. 16± 0. 02,0. 22±0. 05 ; 0. 24±0. 06,0. 33±0. 07, P< 0. 05), while the mRNA expressions of 11β-HSD1 and 11β-HSD2 were unchanged compared with type 2 diabetic group. Conclusions Gossypol can relieve the pathologic changes of nephridial tissue, inhibit the expressions of TGF-β1 and FN through decreasing blood glucose of rats with diabetes mellitus.