洛伐他汀对系膜增生性肾炎大鼠白介素-6及尿蛋白的影响

fEffect of Lovastatin on interleukin-6 secretion and proteinuria in rat with mesangial proliferative nephritis

目的 观察洛伐他汀对系膜增生性肾炎（MsPGN）大鼠模型血与尿白介素-6（IL-6）、尿蛋白、肾功能的影响及对系膜增生的抑制作用。方法 采用慢性血清病性MsPGN大鼠模型，于造模第6周（已出现明显蛋白尿），灌服洛伐他汀（5mg·kg^-1·d^-1混于1．5ml生理盐水中）；对照组灌服等量生理盐水。灌药6周后留取24h尿，从心脏抽血，检测各组24h尿蛋白定量（TP／24h），血与尿IL-6、血尿素氮（BUN）、血肌酐（SCr）、血胆固醇（Tch）及甘油三酯（TG），光镜观察肾脏系膜细胞（MC）及肾小管改变。结果 洛伐他汀组TP／24h、尿及血IL-6、BUN及SCr均显著低于对照组（P〈0．01～0．05）；其MC增生与对照组相比明显减轻，肾小管病变轻微，而两组Tch、TG水平无明显差异（P〉0．05）。结论 洛伐他汀能明显抑制MsPGN大鼠的系膜细胞及基质增生，抑制IL-6的分泌，改善蛋白尿，保护肾功能，且独立于其降脂作用。

Objective To investigate the effect of lovastatin on interleukin-6（IL-6） secretion and proteinuria in rat with mesangial proliferative nephritis. Method Mesangial proliferative nephritis （MsPGN） rat model was induced by producing chronic serum sickness. Six weeks later, rats with obvious proteinurea were treated with lovastatin at a dose of 5 mg · kg ^-1· d ^-1 for another six weeks. The 24-hour urine protein （TP/24h）, IL-6 level in blood and urine, blood urea nitrogen （BUN）, serum creatinine（SCr）,total cholesterol（Tch）, and total triglyceride（TG） were detenmined before animals were sacrificed. The renal histological changes were evaluated by light microscopy. Results TP/24h, blood and urine IL-6 level, BUN and SCr level in lovastatin treated rats were lower as compared to untreated MsPGN rats. There was no difference in Tch and TG level between treated and untreated groups. Lovastatin treatment also improved histological changes such as decrease of mesangial cell proliferation and tubular injury. Conclusions Lovastatin is effective in improving renal pathologic damage, inhibiting IL-6 secretion,and lowering proteinuria in MsPGN rats. The protective effects of lovastatin are independent of its hypolipidemic action.