The effect of oral protease administration in the rat remnant kidney model
The effect of oral protease administration in the rat remnant kidney model
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DOI：
10.1007/s004330050122
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发表时间：
1999-12
期刊：
影响因子：
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通讯作者：
K. Šebeková;J. Dämmrich;Z. Krivosikova;A. Heidland
中科院分区：
文献类型：
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作者：
K. Šebeková;J. Dämmrich;Z. Krivosikova;A. Heidland
已经证明，在不同的动物模型中，腹腔注射蛋白水解酶可以改善肾脏疾病的进展。在本研究中，我们采用大鼠残肾模型来研究口服蛋白水解酶的效果。20只雄性Wistar大鼠接受假手术(CTRL)，25只接受5/6肾切除(5/6 NX)。将大鼠随机分为安慰剂(PL)(2ml自来水/天灌胃)或Phlogenzym(E：固定混合物胰酶2.42 mg、菠萝酶4.54 mg和Rutozid 5.04 mg作为抗氧化剂，每天2ml自来水灌胃)处理组。研究持续时间为45天。大鼠被配对喂养。酶处理对各功能参数和形态参数均有一定的改善作用。在整个研究过程中，5/6 NX组和5/6 NX组大鼠的蛋白尿均较高。应用蛋白水解酶可有效改善其升高(处死时数据：Ctrl-PL 6.27±1.25，CTRL-E 9.27±0.99，5/6 NX-PL 74.04±21.33，5/6 NX-E 39.09±7.93 mg/24 h；P<；0.01)。尿纤维细胞因子转化生长因子-β-1排泄增加(CTRL-PL 0.349±0.051，CTRL-E 0.693±0.230，5/6 NX-PL 3.044±0.540，5/6 NX-E 1.390±0.238 ng/μ肌酐；P<；0.05)。在处死时，用E治疗的大鼠肾小管间质纤维化不那么明显。相应地，5/6 NX-E组大鼠肾皮质肾小管间质组织体积分数明显增加(CTRL-PL 9.9±0.2，CTRL-E 10.0±0.2，5/6 NX-PL 17.9±1.8，5/6 NX-E 13.8±0.9%；P<；0.05)。5/6NX组肾小球和肾小管蛋白质/DNA比值升高，E组有降低趋势。通过血肌酐和尿素水平评估的肾功能不受酶治疗的影响。未观察到两组间的血压差异。总之，口服蛋白水解酶改善了蛋白尿和尿转化生长因子-β的排泄，并改善了肾小管间质纤维化的严重程度，而没有毒性迹象。
It has been demonstrated that intraperitoneal administration of proteolytic enzymes ameliorates the progression of renal diseases in various animal models. In the present study, we employed the rat remnant kidney model to study the effectiveness of oral administration of proteases. Twenty male Wistar rats underwent sham operation (CTRL), while 25 were subjected to 5/6 nephrectomy (5/6 NX). Rats were randomised into placebo (PL) (2 ml tap water/day by gavage), or Phlogenzym (E; fixed mixture of trypsin 2.42 mg, bromelain 4.54 mg, and rutozid 5.04 mg added as antioxidant, in 2 ml tap water daily by gavage) treated group. Duration of the study was 45 days. Rats were pair-fed. Enzyme treatment exerted salutary effects on various functional and morphological parameters. Proteinuria was higher in both 5/6 NX group rats throughout the study. Administration of proteases ameliorated its rise effectively (data at sacrifice: CTRL-PL 6.27±1.25, CTRL-E 9.27±0.99, 5/6 NX-PL 74.04±21.33, 5/6 NX-E 39.09±7.93 mg/24 h;P<0.01). Increased urinary excretion of the fibrogenic cytokine transforming growth factor (TGF-β1) was improved, too (CTRL-PL 0.349±0.051, CTRL-E 0.693±0.230, 5/6 NX-PL 3.044±0.540, 5/6 NX-E 1.390±0.238 ng/μmol creatinine;P<0.05). At sacrifice, tubulointerstitial fibrosis was less pronounced in E-treated rats. Correspondingly, the volume fraction of tubulointerstitial tissue in the renal cortex was improved in 5/6 NX-E rats (CTRL-PL 9.9±0.2, CTRL-E 10.0±0.2, 5/6 NX-PL 17.9±1.8, 5/6 NX-E 13.8±0.9%;P<0.05). The protein/DNA ratio in isolated glomeruli and tubules, as an estimate of glomerular matrix accumulation and hypertrophy of tubules, was enhanced in 5/6 NX groups and a tendency towards lower values was observed after E treatment. Renal function as evaluated by serum creatinine and urea levels was not influenced by the enzyme therapy. No between-group differences in blood pressure were observed. In summary, oral administration of proteolytic enzymes improved proteinuria and urinary TGF-β1excretion, as well as the severity of tubulointerstitial fibrosis without signs of toxicity.