Summary： This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system （RAAS） and clock genes in the kidney. The male Wist...Summary： This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system （RAAS） and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy （STNx） were established. Animals were ran- domly divided into 4 groups： sham STNx group （control）, STNx group, morning benazepril group （MB） and evening benazepril group （EB）. Benazepril was intragastfically administered at a dose of 10 mg/kg/day at 07：00 and 19：00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light：dark cycle of 12：12 for 12 weeks. Systolic blood pressure （SBP）, 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity （RA）, angio- tensin Ⅱ （Ang Ⅱ ） and aldosterone （Aid） by radioimmunoassay （RIA） and the mRNA expression profile of clock genes （bmall, dbp and per2） by real-time PCR at 12 weeks. Our results showed that no signifi- cant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Aid and RA content of a day between the MB group and EB group. The expression peak of bmall mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.展开更多
Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted th...Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction.This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFβ1 in the rodent model of chronic renal failure involving 5/6 nephrectomy.The results showed that irbesartan significantly attenuated th...展开更多
The expression of angiopoietin- 1 （Ang- 1） and thrombospondin- 1 （TSP- 1） in 5/6 subtotal nephrectomy （STN） rats model, and its correlation to the renal microvasculature injury were investigated. Rat 5/6 STN mod...The expression of angiopoietin- 1 （Ang- 1） and thrombospondin- 1 （TSP- 1） in 5/6 subtotal nephrectomy （STN） rats model, and its correlation to the renal microvasculature injury were investigated. Rat 5/6 STN model was established in adult male SD rats, and the sham-operated group and 5/6 STN group were set up. The renal function and histopathological changes were examined at the 1st, 2nd, 4th, 8th and 12th week after operation. The expression orAng-1, TSP-1 and CD31 in renal tissues was detected by using immunohistochemistry. From 2nd to 8th week after operation, Ang-1 was significantly expressed in glomeruli of rats with STN. Ang-1 staining in glomeruli of STN group was increased significantly as compared with that in sham-operated group at 4th and 8th week after operation, and subsequently decreased after the 12th week. The expression of TSP-1 was increased significantly in STN group. As compared with sham-operated group, the CD31 expression was significantly down-regulated from the 2nd week. The expression of Ang-1 mRNA was detected by using RT-PCR at the same time points. The expression of Ang-1 mRNA in renal tissue of rats with STN was significantly up-regulated at the 2nd, 4th and 8th week after operation as compared with that in STN group at other time points or in sham-operated group at the same time points, while decreased evidently at the 12th week as compared with that in sham-operated group. It is concluded that there are changes in the mRNA expression of Ang-1, and the significant up-regulation of the expression of TSP-1 in renal tissue of rats with STN, which may be involved in the remnant renal microvasculature injury.展开更多
Aim Thromboxane A2（TXA2） is assumed to contribute to the process of renal dysfunction. The pres- ent study was designed to investigate whether terutroban, a specific antagonist of thromboxane/prostaglandin？ （TP） ...Aim Thromboxane A2（TXA2） is assumed to contribute to the process of renal dysfunction. The pres- ent study was designed to investigate whether terutroban, a specific antagonist of thromboxane/prostaglandin？ （TP） receptor, protects against renal damage in 5/6 nephrectomy. Methods C57/BL6 mice were randomly grouped into sham-operated （2K）, 5/6 nephroectomy groups （5/6K-off） and 5/6 nephroectomy treated with ter- utroban （10 mg · kg^-1 · d^-l） groups （Yerutroban）. Renal artery and kidney were collected for vascular function study, Western blot, immunohistochemistry （IHC） assay and enzyme-linked immunosorbent assay （ELISA）, re- spectively. Results Four weeks after the surgery, arterial blood pressure was comparable among the three groups. However mice in terutroban group had higher levels of serum creatinine and lower survival. Compared with 2K groups, 5/6K-off mice had significantly higher levels of renal blood flow as well as a blunted relaxation to acetyl- choline. Production of prostacyclin （PGI2） and thromboxane B2 （ TXB2）, but no prostaglandin E2 （ PGE2）, were significantly increased in the renal artery of 5/6K-off group. Terutroban restored the renal blood flow, but not the acetylcholine-induced relaxation in the renal artery. It is probably due to the blockade effect of terutroban on the smooth muscle since terutroban treatment significantly reduced U46619-induced vasconstriction in renal arteries. Interestingly, terutroban increased the production of TXB2, but not PGI2 or PGE2, in the renal artery. This proba-bly is a compensatory effect on prostaglandins production. In kidney cortex, 5/6K-off group had significantly lower levels of PGE2 and TXB2 when compared with 2 K group. Terutroban markedly increased all three prostaglandins levels. Conclusion Terutroban restores renal artery function, but not renal function in mouse with 5/6 nephrecto- my. It suggests that kidney has more complicated regulations than renal artery. High levels of prostanoids in kid- neys may contribute to renal damage in terutroban group. Further experiments will focus on examining the underly- ing mechanisms.展开更多
目的观察复方黄甘对5/6肾切除慢性肾衰模型大鼠的疗效,并探讨其可能的作用机制。方法用HPLC检测复方黄甘提取物组分并定量;构建5/6肾切除大鼠慢性肾衰模型,将模型大鼠随机分为尿毒清组、科素亚组、复方黄甘低、中、高剂量组和模型组,另...目的观察复方黄甘对5/6肾切除慢性肾衰模型大鼠的疗效,并探讨其可能的作用机制。方法用HPLC检测复方黄甘提取物组分并定量;构建5/6肾切除大鼠慢性肾衰模型,将模型大鼠随机分为尿毒清组、科素亚组、复方黄甘低、中、高剂量组和模型组,另加假手术组共7组,每组10只大鼠,经灌胃给药12周后用全自动生化分析仪检测Scr、BUN、Ucr及24 h UPr;对残余肾组织进行HE和Masson染色观察病理变化;用RT-PCR和免疫组化检测肾组织FN、MCP-1、ICAM-1的表达。结果复方黄甘提取物中主要成分及其含量为:甘草苷(0.06%)、丹皮酚(1.06%)、芦荟大黄素(0.1%)、大黄酸(0.47%)、大黄素(0.19%)、大黄酚(0.41%)和大黄素甲醚(0.13%);复方黄甘低、中、高剂量组Scr、BUN、Ucr、Ccr及24h UPr都显著低于模型组(P<0.05);复方黄甘给药组肾小球硬化和肾间质纤维化改善较为明显,且肾组织中FN、ICAM-1 mRNA表达和蛋白表达均显著低于模型组(P<0.05)。结论复方黄甘可改善慢性肾衰模型大鼠肾功能,减轻肾小球硬化和肾间质纤维化,在一定程度上延缓慢性肾功能衰竭的进展。展开更多
基金supported by grants from the Department of Public Health of Hubei Province of China (No. 2012Z-B08)the Health Bureau of Wuhan City of China (No. WX12C10)
文摘Summary： This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system （RAAS） and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy （STNx） were established. Animals were ran- domly divided into 4 groups： sham STNx group （control）, STNx group, morning benazepril group （MB） and evening benazepril group （EB）. Benazepril was intragastfically administered at a dose of 10 mg/kg/day at 07：00 and 19：00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light：dark cycle of 12：12 for 12 weeks. Systolic blood pressure （SBP）, 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity （RA）, angio- tensin Ⅱ （Ang Ⅱ ） and aldosterone （Aid） by radioimmunoassay （RIA） and the mRNA expression profile of clock genes （bmall, dbp and per2） by real-time PCR at 12 weeks. Our results showed that no signifi- cant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Aid and RA content of a day between the MB group and EB group. The expression peak of bmall mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.
基金supported by a grant from Natural Sciences Foundation of Hubei Province,China(No.2008CDB178)
文摘Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction.This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFβ1 in the rodent model of chronic renal failure involving 5/6 nephrectomy.The results showed that irbesartan significantly attenuated th...
文摘The expression of angiopoietin- 1 （Ang- 1） and thrombospondin- 1 （TSP- 1） in 5/6 subtotal nephrectomy （STN） rats model, and its correlation to the renal microvasculature injury were investigated. Rat 5/6 STN model was established in adult male SD rats, and the sham-operated group and 5/6 STN group were set up. The renal function and histopathological changes were examined at the 1st, 2nd, 4th, 8th and 12th week after operation. The expression orAng-1, TSP-1 and CD31 in renal tissues was detected by using immunohistochemistry. From 2nd to 8th week after operation, Ang-1 was significantly expressed in glomeruli of rats with STN. Ang-1 staining in glomeruli of STN group was increased significantly as compared with that in sham-operated group at 4th and 8th week after operation, and subsequently decreased after the 12th week. The expression of TSP-1 was increased significantly in STN group. As compared with sham-operated group, the CD31 expression was significantly down-regulated from the 2nd week. The expression of Ang-1 mRNA was detected by using RT-PCR at the same time points. The expression of Ang-1 mRNA in renal tissue of rats with STN was significantly up-regulated at the 2nd, 4th and 8th week after operation as compared with that in STN group at other time points or in sham-operated group at the same time points, while decreased evidently at the 12th week as compared with that in sham-operated group. It is concluded that there are changes in the mRNA expression of Ang-1, and the significant up-regulation of the expression of TSP-1 in renal tissue of rats with STN, which may be involved in the remnant renal microvasculature injury.
文摘Aim Thromboxane A2（TXA2） is assumed to contribute to the process of renal dysfunction. The pres- ent study was designed to investigate whether terutroban, a specific antagonist of thromboxane/prostaglandin？ （TP） receptor, protects against renal damage in 5/6 nephrectomy. Methods C57/BL6 mice were randomly grouped into sham-operated （2K）, 5/6 nephroectomy groups （5/6K-off） and 5/6 nephroectomy treated with ter- utroban （10 mg · kg^-1 · d^-l） groups （Yerutroban）. Renal artery and kidney were collected for vascular function study, Western blot, immunohistochemistry （IHC） assay and enzyme-linked immunosorbent assay （ELISA）, re- spectively. Results Four weeks after the surgery, arterial blood pressure was comparable among the three groups. However mice in terutroban group had higher levels of serum creatinine and lower survival. Compared with 2K groups, 5/6K-off mice had significantly higher levels of renal blood flow as well as a blunted relaxation to acetyl- choline. Production of prostacyclin （PGI2） and thromboxane B2 （ TXB2）, but no prostaglandin E2 （ PGE2）, were significantly increased in the renal artery of 5/6K-off group. Terutroban restored the renal blood flow, but not the acetylcholine-induced relaxation in the renal artery. It is probably due to the blockade effect of terutroban on the smooth muscle since terutroban treatment significantly reduced U46619-induced vasconstriction in renal arteries. Interestingly, terutroban increased the production of TXB2, but not PGI2 or PGE2, in the renal artery. This proba-bly is a compensatory effect on prostaglandins production. In kidney cortex, 5/6K-off group had significantly lower levels of PGE2 and TXB2 when compared with 2 K group. Terutroban markedly increased all three prostaglandins levels. Conclusion Terutroban restores renal artery function, but not renal function in mouse with 5/6 nephrecto- my. It suggests that kidney has more complicated regulations than renal artery. High levels of prostanoids in kid- neys may contribute to renal damage in terutroban group. Further experiments will focus on examining the underly- ing mechanisms.
文摘目的观察复方黄甘对5/6肾切除慢性肾衰模型大鼠的疗效,并探讨其可能的作用机制。方法用HPLC检测复方黄甘提取物组分并定量;构建5/6肾切除大鼠慢性肾衰模型,将模型大鼠随机分为尿毒清组、科素亚组、复方黄甘低、中、高剂量组和模型组,另加假手术组共7组,每组10只大鼠,经灌胃给药12周后用全自动生化分析仪检测Scr、BUN、Ucr及24 h UPr;对残余肾组织进行HE和Masson染色观察病理变化;用RT-PCR和免疫组化检测肾组织FN、MCP-1、ICAM-1的表达。结果复方黄甘提取物中主要成分及其含量为:甘草苷(0.06%)、丹皮酚(1.06%)、芦荟大黄素(0.1%)、大黄酸(0.47%)、大黄素(0.19%)、大黄酚(0.41%)和大黄素甲醚(0.13%);复方黄甘低、中、高剂量组Scr、BUN、Ucr、Ccr及24h UPr都显著低于模型组(P<0.05);复方黄甘给药组肾小球硬化和肾间质纤维化改善较为明显,且肾组织中FN、ICAM-1 mRNA表达和蛋白表达均显著低于模型组(P<0.05)。结论复方黄甘可改善慢性肾衰模型大鼠肾功能,减轻肾小球硬化和肾间质纤维化,在一定程度上延缓慢性肾功能衰竭的进展。
