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Preeclampsia is the main cause of poor maternal-fetal outcomes. A series of cell and animal experiments, and a small number of clinical studies have shown that pravastatin can prevent and treat preeclampsia by regulating angiogenesis, increasing the expression of heme oxygenase, and stimulating the production of nitric oxide without any reported adverse effects during pregnancy. We review the latest progress on the mechanism, effect, and safety of pravastatin in the prevention and treatment of preeclampsia.
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Objective To investigate the protective effects of astragalosides Ⅳ (ASI) on high glucose-induced renal proximal tubular epithelial cells (NRK-52E).Methods NRK-52E were cultured and divided randomly into three groups:control group,high glucose group (HG in short),ASI groups (with various doses).Cells were treated with increasing concentrations of ASI (20,40,80 and 100 μg/ml) for 24 h in high glucose and we also stimulated cells in ASI 100 μg/ml with high glucose for various lengths of time.The apoptosis rate was detected by flow cytometric analysis.The mRNA and protein expression of transforming growth factor-β1 (TGF-β1),a-smooth muscle actin (α-SMA),Smad2,Smad3 and their phosphorylated forms were detected by real-time polymerase chain reaction (PCR) and Western blot,respectively.Results Compared with the control group,apoptosis was increased in the high glucose group (P ＜ 0.01).However,ASI inhibited high glucose-induced cell apoptosis in a dose-dependent manner,with a maximal inhibitory effect achieved at 100 μg/ml (P ＜ 0.05).The significant inhibition caused by ASI was observed at 8h after the start of pretreatment (P ＜ 0.05) and increased in a time-dependent manner.ASI can inhibit the expression of TGF-β1,α-SMA,Smad2,Smad3 both at mRNA and protein level.Conclusions ASI inhibited NRK-52E cells apoptosis induced by high glucose and reduced expression of TGF-β1,α-SMA,Smad2,Smad3 both at the mRNA and protein level in NRK-52E cells,thus delayed epithelial-to-mesenchymal transition progress.
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Objective To study the effect of astragaloside on TGF-β1,SMAD2/3,and α-SMA expression in the kidney tissue of diabetic KKAy mice,and evaluate its potential role in renal interstitial fibrosis.Methods 20 type 2 diabetic KKAy mice were randomly divided into model group and astragaloside group,while 10 male C57BL/6J mice were selected as the control.Astragaloside at 40 mg · kg-1 · d-1 was given when the KKAy mice fed with high-fat diet to 14 weeks old.The mice in the control and model group received normal saline at 40 mg · kg-1 · d-1.Blood glucose meter was used to detect the blood glucose value of each mice at 16th,20th and 24th week.The mice were killed at 24 weeks old and the kidney tissue samples were collected.Pathology morphological changes were observed.Results (1) blood glucose value:cmpared with the control group,the blood glucose value of KKAy mice at 14 week increased significantly,and that of model group also increased significantly at 16th,20th and 24th week (P＜0.05);the blood glucose value of astragaloside group decreased compared with control group (P＜0.05).(2) Morphology of kidney:in the control group,the glomerular and tubular had clear structure,there was no renal interstitial fibrosis;in the model group,the renal glomerular mesangial matrix had broaden,mesangial cell had increased,renal tubular epithelial cell cytoplasm showed vacuole degeneration,renal interstitial inflammatory cell had increaised.In astragaloside group,there were few renal tubular epithelial cell cytoplasm,and there was no obvious fibrosis.(3)TGF-β1,SMAD2/3,and α-SMA expression levels of the kidney issuse:compared with control group,mice in model group up-regulated TGF-β1,SMAD2/3 and α-SMA expression (P＜ 0.05).TGF-β1,SMAD2/3,and α-SMA expression levels in astragaloside group were significantly lower than those in the model group (P＜0.05).There was few phosphorylated SMAD2/3 expression in renal tubular and glomerular nuclei,while that of model group increased (P＜0.01),and compared with model group,that of the astragaloside group decreased (P＜0.05).Conclusion Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-β/SMADS signaling pathway and down-regulating TGF-β1 and α-SMA expression,thus to relieve renal fibrosis in diabetic mice.