Evidence against increased glomerular pressure initiating diabetic nephropathy.
Evidence against increased glomerular pressure initiating diabetic nephropathy.
复制标题
肾小球压力升高引发糖尿病肾病的证据。
DOI：
10.1038/ki.1987.83
复制
发表时间：
1987
影响因子：
19.6
通讯作者：
Sablay,LB
中科院分区：
文献类型：
--
作者：
Bank,N;Klose,R;Aynedjian,HS;Nguyen,D;Sablay,LB
反对肾小球压力升高引发糖尿病肾病的证据。本研究旨在确定过高的肾小球液压（PG）是否会引发胰岛素依赖型糖尿病大鼠肾小球病理和蛋白尿的发展。正常血压大鼠（WKY）和高血压大鼠（SHR）通过注射链脲佐菌素造成糖尿病。一组SHR糖尿病大鼠用降压药物治疗以降低血压。糖尿病发病一周后，微穿刺法测定PG，结果显示WKY糖尿病组PG高于非糖尿病对照组，SHR糖尿病组PG更高（P < 0.05）。对同样制备的动物组进行了6个月的随访，约为这些大鼠预期寿命的五分之一到三分之一。尾部收缩压测量记录了SHR糖尿病患者的持续严重收缩期高血压，WKY糖尿病患者的正常血压和SHR糖尿病患者持续使用抗高血压药物治疗的低血压。尿蛋白排泄，每月测量，在统计学上是相同的，在所有组中，没有证据表明一个渐进的上升，在SHR糖尿病。糖尿病4个月后，每组两只大鼠的PG测量值与糖尿病1周后的值相似。糖尿病6个月后肾小球系膜扩张的半定量组织学评分未能证明血压正常的WKY糖尿病患者和高血压SHR糖尿病患者之间有任何显着差异。这些观察结果提示PG升高本身并不引起糖尿病肾小球病变或蛋白尿。由于SHR糖尿病患者的肾小球滤过率并不高于WKY糖尿病患者，因此数据不排除肾小球病理和蛋白尿与高血浆流量或滤过率有因果关系的可能性。将血压降低至高血压水平可防止SHR糖尿病患者发生早期糖尿病性肾小球病变。
Evidence against increased glomerular pressure initiating diabetic nephropathy. Studies were carried out to determine whether exaggerated glomerular hydraulic pressure (PG) initiates the development of glomerular pathology and proteinuria in insulin–dependent diabetic rats. Normotensive (WKY) and hypertensive rats (SHR) were made diabetic by streptozotocin injection. One group of SHR diabetic rats was treated with antihypertensive drugs to reduce blood pressure. One week after onset of diabetes, micropuncture determinations of PG, measured by stopped–flow technique, revealed that PG was higher in WKY diabetics than in non-diabetic WKY controls, and that PG was even higher in SHR diabetics (P < 0.05). Similarly prepared groups of animals were followed for six months, approximately one fifth to one third of the expected life span of these rats. Tail systolic blood–pressure measurements documented continuous severe systolic–hypertension in SHR diabetics, normal pressure in the WKY diabetics and hypotension in the SHR diabetics treated continuously with antihypertensive drugs. Urinary protein excretion, measured monthly, was statistically the same in all groups, with no evidence of a progressive rise in the SHR diabetics. PGmeasured in two rats from each group after four months of diabetes was similar to values found after one week of diabetes. Semiquantitative histologic scoring of glomerular mesangial expansion after six months of diabetes failed to demonstrate any significant difference between the normotensive WKY diabetics and the hypertensive SHR diabetics. These observations suggest that elevated PGdoes not in itself initiate glomerular pathology or proteinuria in diabetes. Since the SHR diabetics did not have higher glomerular filtration rates than the WKY diabetics, the data do not exclude the possibility that glomerular pathology and proteinuria are causally related to high plasma flow or filtration rates. Lowering of blood pressure to hypotensive levels in SHR diabetics afforded protection against the development of early diabetic glomerulopathy.