AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conduc...AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit,spectral domain optical coherence tomography(SD-OCT)imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy.RESULTS: A total of 17 eyes of 13 patients treated with25 and 50 mg of oral eplerenone per day were identified.Subretinal fluid(SRF) decreased over time following eplerenone therapy(P = 0.007 and P =0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day181+. SRF diameter decreased from an average of 2174.4μm at baseline to 46.9 μm at day 181 +. Log MAR visual acuity improved from 0.42(Snellen equivalent: 20/53) at baseline to 0.29(Snellen equivalent: 20/39) at day 181 +(P = 0.024). Central subfield thickness(CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+(P = 0.029).CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.展开更多
To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved,36 male Sprague-Dawley rats were randomly divided into control group,adriamycin nephropathy...To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved,36 male Sprague-Dawley rats were randomly divided into control group,adriamycin nephropathy（AN） group and eplerenone-treated group（100 mg.kg-1.d-1 eplerenone）.Blood pressure,24-h urinary protein,serum potassium,sodium and creatinine were measured 28 days after adriamycin injection（a single tail intravenous injection of 6.5 mg/kg adriamycin）.The morphological changes of renal tissues were observed by light and electron microscopy.Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β1 and desmin in renal cortex.The results showed that 28 days after adriamycin injection,there were no significant changes in the level of serum potassium,sodium,creatinine concentrations and blood pressure values in the rats of the three groups.Meanwhile,the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group（P0.01）,but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group（P0.05）.Mild mesangial cell proliferation and matrix expansion,diffuse deformation and confluence of foot processes in podocytes were found in the AN group.By contrast,rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions.The protein expression of TGF-β1 and desmin in the AN group was markedly up-regulated in contrast to that in the control group（P0.01）,whereas that in the eplerenone-treated group was much lower than in the AN group（P0.05）.It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release,and restore the morphology of podocytes independent of its blood pressure-lowing effects.展开更多
A rapid and simple high performance liquid chromatography （HPLC） mcthod wiih a UV detection （241 nm） was developed and validated for estimation of eplerenone from spiked human plasma. The analyte and the internal ...A rapid and simple high performance liquid chromatography （HPLC） mcthod wiih a UV detection （241 nm） was developed and validated for estimation of eplerenone from spiked human plasma. The analyte and the internal standard （valdecoxib） were extracted with a mixture of dichloromethane and diethyl ether. The chromatographic separation was performed on a HiQSil C-18HS column （250 mm × 4.6 mm, 5 um） with a mobile phase consisting of acetonitrile：water （50：50, v/v） at flow rate of 1 mL/min. The calibration curve was linear in the range 100 3200 ng/mL and the heteroscedasticity was minimized by using weighted least squares regression with weighting factor I/X.展开更多
The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to e...The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.展开更多
OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it ...OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it reduces of renal fibrosis.METHODS:Male Wistar rats were randomly divided into 4 groups:the sham group,UUO group(180 d of left ureter ligation),UUO plus eplerenone(EPL)group,and UUO plus HJHR group.After 180 d of oral drug administration,blood and contralateral kidneys were collected for analysis.Angiogenesis-and fibrosis-related indexes were detected.RESULTS:HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels ofα-smooth muscle actin(α-SMA),vimentin and collagen I.Moreover,these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA)by inhibiting the infiltration of macrophages.Furthermore,HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production,which inhibited angiogenesis.Finally,the coexpressions of CD34,CD105 andα-SMA were decreased in the HJHR and EPL groups,indicating that endothelial-to-mesenchymal transition was inhibited.CONCLUSIONS:These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis,encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.展开更多
文摘AIM: To examine eplerenone(Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy(CSCR).METHODS: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit,spectral domain optical coherence tomography(SD-OCT)imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy.RESULTS: A total of 17 eyes of 13 patients treated with25 and 50 mg of oral eplerenone per day were identified.Subretinal fluid(SRF) decreased over time following eplerenone therapy(P = 0.007 and P =0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 μm at baseline to 15.3 μm at day181+. SRF diameter decreased from an average of 2174.4μm at baseline to 46.9 μm at day 181 +. Log MAR visual acuity improved from 0.42(Snellen equivalent: 20/53) at baseline to 0.29(Snellen equivalent: 20/39) at day 181 +(P = 0.024). Central subfield thickness(CST) decreased from 339.5 μm at baseline to 270.3 μm at day 181+(P = 0.029).CONCLUSION: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.
基金supported by grants from the National Natu-ral Sciences Foundation of China (Nos. 30500245, 30871174, and 31050110433)a Medicine-technology Interdiscipline grant from Huazhong University of Science and Technology (No. 2010JC041)
文摘To investigate the protective effects of eplerenone on adriamycin-induced renal injury and the possible mechanisms involved,36 male Sprague-Dawley rats were randomly divided into control group,adriamycin nephropathy（AN） group and eplerenone-treated group（100 mg.kg-1.d-1 eplerenone）.Blood pressure,24-h urinary protein,serum potassium,sodium and creatinine were measured 28 days after adriamycin injection（a single tail intravenous injection of 6.5 mg/kg adriamycin）.The morphological changes of renal tissues were observed by light and electron microscopy.Immunohistochemistry and Western blotting were performed to examine the expression of TGF-β1 and desmin in renal cortex.The results showed that 28 days after adriamycin injection,there were no significant changes in the level of serum potassium,sodium,creatinine concentrations and blood pressure values in the rats of the three groups.Meanwhile,the 24-h proteinuria excretion in the AN group was significantly higher than that in the control group（P0.01）,but that in the eplerenone-treated group was substantially reduced when compared with that in the AN group（P0.05）.Mild mesangial cell proliferation and matrix expansion,diffuse deformation and confluence of foot processes in podocytes were found in the AN group.By contrast,rats in the eplerenone-treated group exhibited obvious attenuation of these morphological lesions.The protein expression of TGF-β1 and desmin in the AN group was markedly up-regulated in contrast to that in the control group（P0.01）,whereas that in the eplerenone-treated group was much lower than in the AN group（P0.05）.It was concluded that eplerenone may ameliorate the proteinuria and the development of pathological alteration in adriamycin-induced nephropathy presumably via the inhibition of cytokine release,and restore the morphology of podocytes independent of its blood pressure-lowing effects.
文摘A rapid and simple high performance liquid chromatography （HPLC） mcthod wiih a UV detection （241 nm） was developed and validated for estimation of eplerenone from spiked human plasma. The analyte and the internal standard （valdecoxib） were extracted with a mixture of dichloromethane and diethyl ether. The chromatographic separation was performed on a HiQSil C-18HS column （250 mm × 4.6 mm, 5 um） with a mobile phase consisting of acetonitrile：water （50：50, v/v） at flow rate of 1 mL/min. The calibration curve was linear in the range 100 3200 ng/mL and the heteroscedasticity was minimized by using weighted least squares regression with weighting factor I/X.
基金supported by National Nature Science Foundation of China(30871083)Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine(BXJ201442)
文摘The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.
基金Natural Science Foundation-funded Project:Effect of Macrophage-to-Myofibroblast Transition in Contralateral Kidney of Unilateral Ureteral Obstruction Rats Through the Aldosterone/MR/SGK1 Pathway and Inhibition of Chinese Herbs(No.81873251)Natural Science Foundation-funded Project:Aldosterone Stimulates MR Activation to Induce Lymphangiogenesis in the Contralateral Kidney of UUO Rats and the Protective Effect of Yiqi Jiedu Huayu Herbs(No.82174317)+1 种基金Hebei Provincial Postgraduate Innovative Ability Cultivation Funding Project:Aldosterone Induced Macrophages to Secrete VEGFA to Participate in Renal Angiogenesis and the Protective Effect of Huoxue Jiedu Huayu Recipe(CXZZBS2023140)Construction Program of New Research and Development Platform and Institution,Hebei Province Innovation Ability Promotion Plan under Grant No.20567624H。
文摘OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it reduces of renal fibrosis.METHODS:Male Wistar rats were randomly divided into 4 groups:the sham group,UUO group(180 d of left ureter ligation),UUO plus eplerenone(EPL)group,and UUO plus HJHR group.After 180 d of oral drug administration,blood and contralateral kidneys were collected for analysis.Angiogenesis-and fibrosis-related indexes were detected.RESULTS:HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels ofα-smooth muscle actin(α-SMA),vimentin and collagen I.Moreover,these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA)by inhibiting the infiltration of macrophages.Furthermore,HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production,which inhibited angiogenesis.Finally,the coexpressions of CD34,CD105 andα-SMA were decreased in the HJHR and EPL groups,indicating that endothelial-to-mesenchymal transition was inhibited.CONCLUSIONS:These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis,encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.
