洛汀新对局灶节段性肾小球硬化大鼠尿液足细胞的影响

目的 探讨尿液足细胞检测在局灶节段性肾小球硬化大鼠（FSGS）中的意义，洛汀新对FSGS大鼠足细胞排泄的影响。方法 42只SD大鼠随机分为实验组和治疗组。行大鼠左肾摘除，术后第7天给予阿霉素5mg／kg尾静脉注射，第28天重复注射阿霉素3mg／kg。第1次注药后1周，治疗组大鼠给予洛汀新3mg／（kg·d）灌胃，实验时间12周。动态检测术后第4、8、12周24h尿蛋白定量（TP／24h），血肌酐（cr），总胆固醇（TC）。间接免疫荧光法检测尿沉渣足细胞特异性标志蛋白（Podocalyxin）以检测尿液中足细胞水平。结果实验组大鼠各时间点TP／24h、Cr、TC均较同期治疗组升高，随时间进展同组各指标亦逐渐升高，部分有显著性差异。实验组第4、8、12周尿足细胞分别为（0．46±0．22）个／ml、（2．70±0．92）个／ml、（4．26±1．30）个／ml。治疗组分别为（O．0±0．O）个／ml、（1．03±0．70）个／ml、（2．49±1．01）个／ml。同一时间点两组尿液足细胞相比分别有显著差异（P〈O．01）。实验组大鼠肾组织病理损害呈进行性进展，第4周系膜细胞、系膜基质轻度增加；第8周系膜增生加重，部分肾小球出现节段硬化；第12周65％肾小球节段硬化，少数呈球性硬化。而治疗组肾病理改变较轻。尿足细胞数与肾小球硬化指数显著正相关，亦与TP／24h正相关。结论单侧肾切除加重复阿霉素注射可成功诱导肾硬化大鼠模型。尿液中脱落足细胞检测可作为判断FSGS病情活动性的标志之一。洛汀新可减少FSGS大鼠尿液足细胞的排泄而有肾保护作用。

Effect of Lotensin on Urinary Podocytes in Rats with Focal Segmental Glomerulosclerosis

Objective To investigate the clinical significance of the urinary podocytes excretion and the effect of lotensin on urinary podocytes excretion in rats with focal segmental glomerulosclerosis. Methods Forty-two male Wistar rats were randomly divided into experimental group and lotensin-treated group. The rats in experimental group were given intravenous injection of 5 mg/kg Adriamycin （ADR） on day 7 and 3 mg/kg ADR on day 28 after the left nephrectomy. The rats in lotensin-treated group intragastrically received 3 mg/ （kg.d） lotensin daily one week after the first injection of ADR for 12 weeks. 24-hour proteinuria （TP/24h）, serum creatinine （Scr）, total cholesterol （TC） and urinary podocytes were measured dynamically on the 4th, 8th and 12th week. Podocyte-specific marker protein-podocalyxin （PCX） was detected by immunofluorescene. Results The urinary TP/24h, Scr, TC in experimental rats increased progressively, and some were significantly higher than those in lotensin-treated rats. Urinary podocytes at the 4th, 8th and 12th week were （0. 46 ＋ 0. 22）/ml, （2. 70 ＋ 0. 92）/ml and （4. 26 ＋ 1.30）/ml in experimental rats, and （0. 0 ＋ 0. 0）/ml, （ 1.03 ＋ 0. 70）/ ml, （2. 49 ＋ 1.01）/ml in lotensin-treated rats, with significant difference between the two groups at the same time point （P〈0. 01）. In experimental rats, mild hyperplasia was observed in mesangial cells （MC） and extracellular matrix （ECM） at 4th week, aggravated hyperplasia and some segmental sclerosis at 8th week, about 65% segmental sclerosis at 12th week. The renal lesions were less severe in lotensin-treated than those in experimental group. A significant positive correlation was found between the number of urinary podocytes and the glomerulosclerotic indexes, TP/24h. Conclusion The accelerated nephrosclerosis can be induced by nephrectomy combined with repeated intravenous injection of Adriamycin in rats. Urinary podocytes can be one of the markers to predict the development of focal