苦瓜总皂苷对盐敏感高血压所致肾脏损害大鼠肾脏组织中podocin和nephrin表达的影响

The effects of bitter gourd saponins on the expression of podocin and nephrin in renal tissues of rats with renal damage induced by salt-sensitive hypertension

目的研究苦瓜总皂苷对高盐饮食诱导的盐敏感肾脏损害大鼠的治疗作用并分析其可能机制。方法 50只SD大鼠适应性喂养10 d后随机分为正常组、模型组以及苦瓜总皂苷低、中、高剂量治疗组,每组10只,除正常组外,其余四组给予高盐饲料(4. 0%高盐饲料)诱导盐敏感肾脏损害大鼠模型,4周后检验造模是否成功,造模成功后正常组和模型组给予1. 0 ml/(kg·d)生理盐水灌胃,苦瓜总皂苷三个剂量组分别给予苦瓜总皂苷10、20、40 mg/(kg·d)灌胃。治疗8周后处死大鼠,收集尿液检测24 h尿蛋白和尿肌酐,收集血清测定血肌酐、血清醛固醇、血清钠和血清钾变化特点,同时收集肾脏检测肾病组织病理学及肾脏中裂孔隔膜蛋白(podocin)和足细胞蛋白(nephrin)表达特点。结果模型组病理学检测有明显肾小球硬化和肾间质纤维化,治疗组明显改善;正常组收缩压维持在120 mm Hg左右,模型组则维持在170 mm Hg左右,苦瓜总皂苷三个剂量治疗组相较于模型组明显降低(P <0. 05);各组间生化和尿检测相关指标比较,血清钠和血清钾差异无统计学意义(P> 0. 05),与正常组比较,模型组血清肌酐和24 h蛋白尿/尿肌酐明显升高(P <0. 05),而肌酐清除率以及醛固醇明显降低(P <0. 05),苦瓜总皂苷治疗组上述指标较模型组明显改善;与正常组相比,模型组Podocin和Nephrin蛋白和mRNA表达均明显降低(P <0. 05),苦瓜总皂苷治疗组较模型组明显升高(P <0. 05)。结论苦瓜总皂苷可明显改善高盐诱导所致高血压肾脏损害大鼠的病理生理,这可能与其可调节肾脏组织podocin和nephrin表达,进而抑制肾小球硬化,改善肾脏间质纤维化有关。

Objective To study the therapeutic effect of bitter gourd saponins on salt-sensitive kidney injury induced by high salt diet and its possible mechanism. Methods 50 Sprague Dawley （SD） rats were randomly divided into normal group, model group and low-dose, middle-dose and high-dose treatment group after 10 days of adaptive feeding. Each group had 10 rats. Except the normal group, the other four groups were given high salt diet （4. 0% high salt diet） to induce salt-sensitive kidney damage in rats. The normal group and the model group were given 1.0 m/（ kg ·d） normal saline, and the three dosage groups of total saponins of balsam pear were given 10 mg/（ kg·d）, 20 mg/（ kg· d） and 40 mg/（ kg · d） respectively. After 8 weeks of treatment, rats were sacrificed and collect the 24-hour proteinuria, creatinine. Serum creatinine, serum aldosterone, serum sodium and serum potassium were measured, and renal histopathology and the expression of podocin and nephrin were detected. Results Pathological examination of model group showed obvious glomerular sclerosis and renal interstitial fibrosis, and glomerular sclerosis in the treatment group was obviously improved by bitter gourd saponins; The systolic pressure in the model group was 170 mmHg, significantly higher than that of the normal and treatment groups, the systolic blood pressure of the treatment groups were obvious decreased when treated by bitter gourd saponins （P 〈 0. 05 ） ; Compared with normal group, serum creatinine and 24 h proteinuria / urine creatinine in model group were significantly increased （ P 〈 0. 05 ）, while creatinine clearance rate and aldosterone were significantly decreased （ P 〈 0.05 ）, and the above indexes in bitter gourd saponins treatment group were significantly improved; Compared with the model group, the protein and mRNA expression of podocin and nephrin were significantly decreased （ P 〈 0.05 ） , while the two indexes can be revered by bitter gourd saponins in treat- ment group （ P 〈 0.05 ）. Conclusions The bitter gourd saponins can significantly improve the symptoms of salt-induced hypertensive nephropathy in rats, which may be related with the expression of podocin and nephrin in renal tissue, thereby inhibiting glomerulosclerosis and improving renal interstitial fibrosis.