Schwartz M M, Bidani A K
Department of Pathology, Rush Medical College, Chicago, Illinois.
Kidney Int. 1991 Aug;40(2):226-37. doi: 10.1038/ki.1991.204.
The pathogenetic significance of changes in mesangial structure and function were studied in hypertensive (HT) (BP +/- SD = 173 +/- 23 mm Hg, N = 13) and normotensive (NT) (130 +/- 17 mm Hg, N = 12) WKY rats with 5/6 nephrectomy and compared to sham-operated controls (SHAM) (121 +/- 11 mm Hg, N = 12). Rats were fed a 24% protein diet and studied six to eight week after surgery. Acute glomerular necrosis was present in 6/13 HT, 1/12 NT, and 0/12 SHAM, and glomerular sclerosis was seen in 7/13 HT, 4/12 NT, and 0/12 SHAM. HT and NT had glomerular and tubular hypertrophy compared to SHAM (mean glomerular diameter +/- SD. HT = 174 +/- 17 mu and NT = 171 +/- 12 cf. SHAM = 142 +/- 11, P = 0.0012, ANOVA). The fractional mesangial volumes, determined by ultrastructural morphometry, were similar in all groups, but the absolute volumes were increased in the HT and NT (HT = 323 +/- 103 mu3 x 10(-3) and NT = 335 +/- 75 cf. SHAM = 164 +/- 20, P = 0.01, ANOVA). Mesangial clearance of aggregated rat IgG (AgRalgG) was studied in serial biopsies by immunofluorescence microscopy. Following i.v. injection, mesangial AgRalgG appeared increased in HT and NT over SHAM for four hours, but after 24 hours, the label had disappeared from the mesangium in all groups. We conclude that neither increased mesangial volume nor abnormalities of mesangial clearance of macromolecules plays a role in the pathogenesis of the acute, necrotizing glomerular lesion which was mainly seen in HT rats. On the other hand glomerular sclerosis, seen in both NT and HT rats but not sham controls, may result from more than one mechanism. In the HT rats scarring may result from healing of the acute glomerular lesions. Although we have excluded the mesangial clearance function as a factor in the pathogenesis of glomerular sclerosis, the presence of glomerular scarring in NT rats suggests that the lesions may result from dysfunction of other glomerular cells or unmeasured mesangial cell functions.
在接受5/6肾切除的高血压（HT）（血压±标准差 = 173±23 mmHg，n = 13）和正常血压（NT）（130±17 mmHg，n = 12）WKY大鼠中，研究了系膜结构和功能变化的发病机制意义，并与假手术对照组（SHAM）（121±11 mmHg，n = 12）进行比较。大鼠喂食24%蛋白质饮食，并在手术后6至8周进行研究。13只HT大鼠中有6只、12只NT大鼠中有1只、12只SHAM大鼠中无1只出现急性肾小球坏死，13只HT大鼠中有7只、12只NT大鼠中有4只、12只SHAM大鼠中无1只出现肾小球硬化。与SHAM相比，HT和NT出现肾小球和肾小管肥大（平均肾小球直径±标准差。HT = 174±17μm，NT = 171±12，相比SHAM = 142±11，P = 0.0012，方差分析）。通过超微结构形态计量学确定的系膜分数体积在所有组中相似，但HT和NT组的绝对体积增加（HT = 323±103μm³×10⁻³，NT = 335±75，相比SHAM = 164±20，P = 0.01，方差分析）。通过免疫荧光显微镜在系列活检中研究了聚集的大鼠IgG（AgRalgG）的系膜清除情况。静脉注射后，HT和NT组系膜中的AgRalgG在4小时内比SHAM组增加，但24小时后，所有组系膜中的标记物均消失。我们得出结论，系膜体积增加和大分子系膜清除异常在主要见于HT大鼠的急性坏死性肾小球病变的发病机制中均不起作用。另一方面，NT和HT大鼠均出现但假手术对照组未出现的肾小球硬化可能由多种机制导致。在HT大鼠中，瘢痕形成可能源于急性肾小球病变的愈合。虽然我们已排除系膜清除功能作为肾小球硬化发病机制的一个因素，但NT大鼠中存在肾小球瘢痕提示病变可能源于其他肾小球细胞功能障碍或未测量的系膜细胞功能。
