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
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。
