AIM:To study the effects of astragali radix extract(ARE)on renal resistance to atrial natriuretic peptide(ANP)in rats with experimental nephrotic syndrome.METHODS:Male Sprague-Dawley rats were randomly divided into normal control,adriamycin nephropathy(ADR),ADR treated with ARE(2.5 g? kg-1? d-1)and ADR treated with benazepril(10 mg? kg-1? d-1).After 6 weeks,rats received intravenous infusion of 2% body weight isotonic saline.Urinary cGMP excretion(UcGMPV),plasma ANP level,renal PDE5 activity and protein expression were also detected.RESULTS:ARE increased UNaV while ACEI was not natriuretic.Nephrotic rats had a blunted natriuretic response and reduced rate of UcGMPV after volume expansion despite higher plasma ANP concentration.ARE increased UcGMPV and restored partly natriuretic response to volume expansion.The activity and protein abundance of renal PDE5 were high in nephrotic rats.ARE significantly reduced the PDE5 activity and protein expression.CONCLUSION:ARE may ameliorate the renal resistance to ANP in rats with adriamycin nephropathy by inhibiting the PDE5.

Objective To investigate the incidence of contrast-induced nephropathy (CIN) in the elderly undergoing coronary angiography and the correlated clinical risk factors.Methods 0.90% sodium chloride (1 ml · kg~-1 · h~-1 ) was administered 6 hours before and 12 hours after contrast media administration for 195 elderly patients,and the dose of sodium chloride was half when the patients were suffering from severe congestive heart failure.The levels of serum creatinine (Scr) and cystatin C were measured 3 days before and on the 2nd,5th day after the administration of contrast,respectively .Results(1) The incidence of CIN was 8.7% (17/195).The renal function of 11 cases recovered to baseline level 3 months after the use of contrast,2 cases had transformation to chronic renal failure but without undergoing maintenance hemodialysis,and 3 cases were dependent on maintenance hemodialysis,while 1 case developed multiple organ dysfunction until death.(2) There was no significant difference between pre-and post-contrast administration in the level of cystatin C (t=O.137,P= 0.891). But the concentration of Scr was reduced significantly on the 2nd day compared with the baseline (t=4.776,P = 0.000).Both the cystatin C and Scr recovered to the baseline on the 5th day.(3) There were no significant differences between the CIN and non-CIN group in gender,the dose of contrast,the baseline Scr,and the proportion of coronary heart disease.But there were significant differences in age,the baseline serum cystatin C,the proportions of diabetes mellitus,hypertension and congestive heart failure.(4) The clinical risk factors of CIN were the baseline Scr (OR = 1.039),the baseline serum cystatin C (OR=6.654),diabetes mellitus (OR=8.104) and congestive heart failure (OR=9.597) according to the analysis of logistic regression.ConclusionsWith the hydration and the use of low-osmolar nonionic contrast,it is safe to receive contrast examination for the elderly patients.The baseline serum levels of Scrand cystatin C,diabetes mellitus and congestive heart failure are the clinical risk factors of CIN.Compared with Scr,serum cystatin C is the more powerful predictor for the development of CIN.

ObjectiveTo study the effect of astragaloside Ⅳ(AS-Ⅳ) on glucose-induced podocyte adhesion and its possible mechanism. MethodsConditionally immortalized mouse podoeytes were treated with 10, 50, 100 mg/L AS-Ⅳ and with 100 mg/L AS-Ⅳ for 3, 6, 12, 24 h. Cell attachment was measured by fluorescence and centrifugation cell adhesion assays, respectively. Expression of α3β1 integrin mRNA and protein was examined by real-time PCR and Western blot. ResultsHigh glucose induced a significant reduction in adherent podocytes compared to normal glucose group (P<0.05). AS-Ⅳ improved high glucose-induced podocyte adhesion in a time- and dose-dependent manner. Real-time PCR and Western blot analysis revealed that high glucose-induced down-regulation of α3β1 integrin in podocytes were significantly meliorated by AS-Ⅳ (P<0.05). ConclusionAstragaloside Ⅳ improved high glucose-induced podocyte adhesion which may be mediated through α3β1 integrin up-regulation.

【Objective】 To investigate the protection of astragaloside IV from high glucose induced podocyte injury and mitochondrial dysfunction and its molecular mechanisms. 【Methods】 The model of podocyte injury induced by high glucose (30 mmol/L glucose) was established, and the model cells were treated with low, medium and high doses of astragaloside IV respectively; cell activity was detected by CCK-8. Apoptosis was detected by TUNEL staining. Mitochondrial membrane potential was detected by JC-1 fluorescence probe. ATP content was detected by the kit. The expression levels of apoptosis and podocyte injury related proteins and Notch pathway related proteins were detected by Western blotting. 【Results】 Compared with the control group, cell activity was decreased, apoptosis level was increased (P<0.05), anti-apoptotic protein (Bcl2) expression was decreased, and apoptosis protein (Bax, cleaved-caspase 9, cleaved-caspase 3) expressions were increased (all P<0.05) in HG group. Compared with HG group, HG+AS-IV improved cell activity and apoptosis level induced by high glucose (P<0.05), increased expression of anti-apoptotic protein (Bcl2), and decreased expressions of apoptotic protein (Bax, cleaved-caspase 9, and cleaved-caspase 3) (all P<0.05). Compared with the control group, mitochondrial dysfunction occurred in HG group, JC-1 monomer content increased, and ATP content decreased (all P<0.05). Compared with HG group, HG+AS-IV improved mitochondrial dysfunction, increased JC-1 polymer content and ATP content (P<0.05). In addition, compared with the control group, the expression of Notch pathway-related protein was decreased in HG group (P<0.05). Compared with HG group, Notch pathway-related protein expression was increased in HG+AS-IV group (all P<0.05). Molecular docking results showed that AS-IV could bind Notch1. 【Conclusion】 Astragaloside IV can improve podocyte injury and mitochondrial dysfunction induced by high glucose, possibly by inhibiting Notch pathway activation.