Falk S A, Buric V, Hammond W S, Conger J D
Department of Medicine, University of Colorado Health Sciences Center, Veterans Administration Medical Center, Denver.
Am J Kidney Dis. 1991 Feb;17(2):218-27. doi: 10.1016/s0272-6386(12)81132-2.
Serial measurements were performed in Munich-Wistar rats with five-sixths nephrectomy that had undergone prior selective thyroidectomy (Tx group) or thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal failure progression. At 1 week, inulin clearance rates (Cin) in TxT4 and Tx rats were 0.367 +/- 0.171 and 0.120 +/- 0.036 mL/min, respectively, different at P less than 0.01. Corresponding single-nephron filtration rate (SNGFR), glomerular plasma flow (QA), glomerular transcapillary hydraulic pressure (delta P), and proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats (P less than 0.01). Protein excretion (UPROT) was 151 +/- 40 in TxT4 rats, and 9 +/- 5 mg/d in Tx animals. Glomerular mesangial matrix expansion and focal tubulointerstitial changes were more frequent in TxT4 than Tx rats. By 4 weeks, Cin, SNGFR, QA, glomerular ultrafiltration coefficient (Kf) and Jv were similar in Tx and TxT4. Only glomerular capillary pressure (PGC) remained lower in Tx rats (35 +/- 3 v 50 +/- 3 mm Hg in TxT4, P less than 0.001). UPROT was 161 +/- 24 in TxT4 and 17 +/- 12 mg/d in Tx rats. While 7% +/- 4% of glomeruli showed focal sclerosis in TxT4 rats, there was none in the Tx group. Maximal glomerular planar area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group. However, this measurement was not significantly different between TxT4 and Tx glomeruli at 1 or 4 weeks. Minimal focal tubulointerstitial changes were found in TxT4, but there were not progressive from those observed at 1 week. The reduced PGC at 1 week was the result of a disproportionately greater increase in afferent (RA) than efferent arteriolar resistance (RE) in Tx rats (P less than 0.025); however, at 4 weeks, both RA and RE had decreased to values identical to those in TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean arterial pressure. In conclusion, a reduced PGC was the sole functional correlate of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial nephrectomy model. Suppression of either nephrectomy-related hypertrophy or tubulointerstitial injury by Tx could not be excluded as at least partially protective factors.
对慕尼黑-威斯塔大鼠进行了系列测量，这些大鼠接受了六分之五肾切除术，且之前进行过选择性甲状腺切除术（Tx组）或甲状腺切除术后进行甲状腺素替代治疗（TxT4组），以确定甲状腺切除术对肾小球和肾小管动力学的影响，以及其与甲状腺切除术减轻肾衰竭进展的关系。在第1周时，TxT4组和Tx组的菊粉清除率（Cin）分别为0.367±0.171和0.120±0.036 mL/分钟，差异有统计学意义（P<0.01）。与TxT4组大鼠相比，Tx组的相应单肾单位滤过率（SNGFR）、肾小球血浆流量（QA）、肾小球跨毛细血管液压（ΔP）和近端肾小管重吸收（Jv）均降低（P<0.01）。TxT4组大鼠的蛋白排泄量（UPROT）为151±40，Tx组动物为9±5 mg/d。TxT4组比Tx组肾小球系膜基质扩张和局灶性肾小管间质改变更常见。到第4周时，Tx组和TxT4组的Cin、SNGFR、QA、肾小球超滤系数（Kf）和Jv相似。只有Tx组大鼠的肾小球毛细血管压力（PGC）仍然较低（TxT4组为50±3 mmHg，Tx组为35±3 mmHg，P<0.001）。TxT4组大鼠的UPROT为161±24，Tx组大鼠为17±12 mg/d。TxT4组大鼠中有7%±4%的肾小球出现局灶性硬化，而Tx组没有。TxT4组的最大肾小球平面面积在1至4周之间增加，而Tx组没有。然而，在第1周或第4周时，TxT4组和Tx组的肾小球之间这一测量值没有显著差异。TxT4组发现有最小程度的局灶性肾小管间质改变，但与第1周观察到的相比没有进展。第1周时PGC降低是因为Tx组大鼠入球小动脉阻力（RA）的增加比例大于出球小动脉阻力（RE）（P<0.025）；然而，在第4周时，RA和RE均降至与TxT4组动物相同的值，Tx组大鼠较低的PGC是平均动脉压降低的结果。总之，在这个部分肾切除模型中，PGC降低是甲状腺切除术导致蛋白尿减少和肾小球硬化减轻的唯一功能相关因素。不能排除甲状腺切除术抑制肾切除相关的肥大或肾小管间质损伤至少是部分保护因素。
