Drüeke T, Hennessen U, Nabarra B, Ben Nasr L, Lucas P A, Dang P, Thomasset M, Lacour B, Coudrier E, McCarron D A
INSERM Unité 90, Unité 25, Hôpital Necker, Paris, France.
Kidney Int. 1990 Jun;37(6):1438-48. doi: 10.1038/ki.1990.134.
Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.
与基因对照品系Wistar Kyoto大鼠(WKY)相比,自发性高血压大鼠(SHR)的肠道钙转运、肾小管钙重吸收以及血浆1,25-二羟维生素D3(骨化三醇)水平均有所降低。在本研究中,通过电子显微镜检查了12至14周龄雄性SHR和WKY的十二指肠吸收上皮和肾小管上皮,以确定此类功能紊乱是否与结构异常有关。在SHR中观察到十二指肠和近端肾小管上皮的微绒毛有片状缺失,而WKY的刷状缘膜完全正常。在SHR肠上皮细胞的基底与基底膜之间观察到不规则间隙。此外,SHR十二指肠和肾微绒毛的平均高度降低。测定了刷状缘膜的两种特异性标志物碱性磷酸酶和绒毛蛋白,以及细胞质维生素D依赖性钙结合蛋白CaBP9K和CaBP28K。与WKY相比,SHR十二指肠碱性磷酸酶活性降低:0.145±0.002对0.186±0.002国际单位/分钟·微米³×10³刷状缘,均值±标准误,N = 10对,P<0.001。然而,十二指肠绒毛蛋白表达与WKY无差异。SHR十二指肠CaBP9K和肾CaBP28K含量降低:分别为21.0±0.80对29.9±2.19微克/毫克蛋白,N = 6对,十二指肠P<0.01;以及4.47±0.39对7.67±0.54微克/毫克蛋白,N = 6对,肾脏P<0.001。这些数据表明SHR肠道和肾细胞存在结构和功能异常,似乎反映了转运上皮的紊乱,这可能是内在性的,也可能与循环骨化三醇减少有关。