Endothelin-1-mediated alteration of metallothionein and trace metals in the liver and kidneys of chronically diabetic rats.
Endothelin-1-mediated alteration of metallothionein and trace metals in the liver and kidneys of chronically diabetic rats.
复制标题
内皮素-1介导的金属硫蛋白和痕量金属的变化在慢性糖尿病大鼠的肝脏和肾脏中。
DOI：
10.1080/15604280214281
复制
发表时间：
2002-07
期刊：
影响因子：
--
通讯作者：
Chakrabarti, Subrata
中科院分区：
文献类型：
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作者：
Cai, Lu;Chen, Shali;Evans, Terry;Cherian, M George;Chakrabarti, Subrata
本研究观察了内皮素-1（ET-1）对链脲佐菌素（STZ）诱导的糖尿病大鼠肝、肾金属硫蛋白（MT）及微量金属元素（Zn、Cu、Fe）的影响。在6个月的随访后，对糖尿病大鼠、年龄和性别匹配的对照组以及使用双重ETA/ETB受体阻滞剂波生坦的对照组和糖尿病动物进行了研究。MT测定采用镉-血红素法。用原子吸收光谱仪测量金属。采用逆转录聚合酶链反应（RT-PCR）技术检测ET-1 mRNA的表达。糖尿病大鼠肝、肾组织ET-1 mRNA表达较对照组明显增加，沿着肝、肾组织MT蛋白表达的增加。肝脏MT蛋白水平的增加与肝脏铜和铁的减少有关，而肾脏MT的增加与肾脏铜和铁积累的增加有关。锌水平在糖尿病大鼠的两个器官中没有改变。波生坦治疗可部分预防肝脏和肾脏中MT水平的升高，沿着血清肌酐降低和尿肌酐水平升高。进一步波生坦治疗纠正了糖尿病大鼠肾脏中增加的Cu和Fe水平，但降低了肝脏Cu和Fe水平。未观察到波生坦治疗对非糖尿病大鼠的显著影响。这些数据表明，糖尿病中ET拮抗作用的可能影响可能是通过MT和微量金属的变化介导的。
In the present study, the role of endothelin-1 (ET-1) on alterations of hepatic and renal metallothionein (MT) and trace metals (Zn, Cu, and Fe) were investigated in streptozotocin (STZ)- induced diabetic rats. Diabetic rats, age- and sex-matched controls, as well as control and diabetic animals on a dual ETA/ETB receptor blocker, bosentan, were investigated after 6 months of follow-up. MT was measured by cadmium-heme assay. Metals were measured by atomic absorption spectrometer. ET-1 mRNA was analyzed by reverse transcriptase–polymerase chain reaction (RT-PCR) technique. Hepatic and renal ET-1 mRNA was increased in diabetic rats as compared to control rats, along with an increase in both hepatic and renal MT proteins. The increased hepatic MT protein level was associated with decreases in hepatic Cu and Fe, whereas increased renal MT was associated with increases in renal Cu and Fe accumulation. Zn levels were unaltered in both organs in diabetic rats. Bosentan treatment partially prevented the increase in MT levels in both liver and kidney, along with reduced serum creatinine and increased urinary creatinine levels. Further bosentan treatment corrected the increased Cu and Fe levels in the kidney in diabetic rats, but reduced hepatic Cu and Fe levels. No significant effects of bosentan treatment on nondiabetic rats were observed. The data suggest that the possible effects of ET antagonism in diabetes may be mediated via changes in MT and trace metals.