【摘 要】
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OBJECTIVE The effect of pentamathylquercetin (PMQ) on renal fibrosis in diabetic GK rats was investigated.METHODS Male GK rats and age-matched male Wistar rats were used.GK rats were divided into four
【机 构】
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Department of Pharmacology, Basic Medical School, Tongji Medical College, Huazhong University of Sci
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OBJECTIVE The effect of pentamathylquercetin (PMQ) on renal fibrosis in diabetic GK rats was investigated.METHODS Male GK rats and age-matched male Wistar rats were used.GK rats were divided into four groups which were fed by normal or drug-containing food, resulting in daily PMQ intake of 0, 5, 10 or 20 mg·kg-1 , respectively, for 16 weeks.At the end of the experimental period, urine was collected for 24 h from rats kept in metabolic cages.Then the rats were sacrificed to obtain kidneys and blood samples.The changes of kidney weight/body weight (KW/BW), urine albumin excretion rate (UAER) and creatinine clearance rate (Ccr) were determined.The morphology of glomeruli was observed by Masson staining.Furthermore,immunohistochemistry was carried out to measure TGF-β, Smad7 and collagenⅣ, TGF-β was also measured by enzyme linked immunosorbent assay (ELISA).RESULTS Compared with Wistar rats, the levels of KW/BW (from 5.35 to9.15), UAER (from46.1 to49.8 mg/24 h), Ccr (from 0.43 to 0.67 ml·min-1), glomerular fibrosis (increased 95.3%), TGF-β (increased 33.7% for immunohistochemistry and 48.2% for ELISA) and collagenⅣ (increased 25.9%) were markedly enlarged in the model group, while the Smad7 level was reduced(by 16.1%).However, the renal fibrosis was ameliorated with suppression of TGF-β/Smads signaling after PMQ treatment.Take the group of PMQ 10 mg·kg-1 for example.The levels of KW/BW (from 9.15 to 7.99) , UAER (from 49.8 to 40.2 mg/24 h), Ccr (from 0.67 to 0.49 ml·min-1), glomerular fibrosis (decreased 61.8%), TGF-β (decreased 8.3% for immunohisto-chemistry and 58.9% for ELISA), collagenⅣV (decreased 28.7%).Smad7 level was increased (by 33.4%).CONCLUSION TGF-β/Smads signaling has been activated in the kidney of GK rats, which showed typical renal dysfunction and fibrosis.After treatment with PMQ, this signaling was suppressed and renal fibrosis was significantly ameliorated.This effect of PMQ may be a result of increased SmadT.
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