人参皂苷Rg1减轻肾病综合征肾气虚模型大鼠肾损伤的作用及机制
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摘要
目的：
1.观察人参皂苷Rgl对肾病综合征肾气虚模型大鼠血生化、肾功能以及肾组织病理的影响以探讨其对肾是否有保护作用。
2.通过检测模型大鼠炎症因子白介素-4(IL-4)、肿瘤坏死因子－α (TNF－α)血清浓度来探索人参皂苷Rgl对肾具有保护作用的机制。
3.探讨人参补元气与调节炎症因子的关系。
方法：
40只雄性SD大鼠,正常组8只,其余采用盐酸多柔比星(5.0mg/kg)尾静脉注射,给药后采用慢性悬尾应激法强化肾气虚模型,造模后老鼠处于蜷缩状态,且疲乏无力,14天后,出现尿蛋白定量>100mg/24h提示模型复制成功,计入实验。随机分为模型组、人参皂苷Rgl低剂量组、人参皂苷Rgl高剂量组,每组各8只。观察一般状态,测体重,用代谢笼收集24h尿液,记录尿量行24h尿蛋白定量。检测肾功能。采用酶联免疫吸附法(ELISA)检测血清IL－4、TNF－α浓度。光镜及电镜观察肾组织的病理变化。
结果：
1.模型组大鼠一般状态差,各组大鼠体重增长无明显差异(P>0.05)。2.肾病大鼠模型组分组后第7天开始出现蛋白尿,14天后尿蛋白明显增加,28天达到高峰,与正常对照组相比,差异有显著性意义(p<0.01)。人参皂苷Rg1低剂量治疗组第7天尿蛋白比模型组稍减少(P<0.05),高剂量组减少明显(p<0.01),治疗组第14天,28天尿蛋白进一步减少,与模型组相比,差异有显著性意义(P<0.01)。3.模型组大鼠在分组28天后血清总蛋白(TP)、白蛋白(ALB)降低,胆固醇(CH)、甘油三酯(TG)增加,与正常组比较差异有显著统计学意义(P<0.01),人参皂苷组血清TP、ALB升高,CH、TG降低,与模型组比较差异有显著统计学意义(P<0.01)。各组血清尿素(BUN)、肌酐(Scr)无明显差异(P>0.05)。4.与正常组比较,模型组大鼠血清IL－4、TNF－α浓度均显著增加(P<0.01),人参皂苷Rg1组IL-4较模型组显著减少(P<0.01),但仍比正常组高(P<0.05),人参皂苷Rg1低剂量、高剂量组TNF－α均较模型组显著减少(P<0.01),与正常组比较无统计学意义。5.模型组大鼠足突融合,电镜显示比治疗组明显。
结论：
1.人参皂苷Rg1改善肾病综合征肾气虚模型大鼠血生化、肾功能以及肾足细胞病变,对肾组织有保护作用,根据其临床症状的改善表明能补肾气。
2.人参皂苷Rg1对肾组织具有肾保护作用的机制与降低血清炎症因子IL－4、TNF－α浓度有关。
3.依据人参的提取成分人参皂苷Rgl降低炎症因子浓度的同时改善肾气虚模型大鼠临床症状可以推测人参补元气的机制包括调节免疫。
Objectives:
1. To investigate the effects of Ginsenoside Rgl on serum biochemical index, renal function, and renal pathology in rats with nephropathy.
2.To detect the rats' serumlevel of IL-4and TNF-α and explor the ginsenoside Rgl's protective mechanism to kidney.
3.To study the correlation relationship between ginseng tonifying primordial Qi and regulating inflammatory factors.
Methods:
Random samplled eight rats for normal group from Forty male SD rats, the other were injected adriamycin(5mg/kg) in caudal vein once,and be hang the tail twice every day to reinforce the Kidney-Qj Deficiency model. The normal group were injected equivalent normal saline, After two weeks, the model rats curled up in a state and were lassitude,24h proteinuria was more than100mg,then the models were copied successfully. Random samplled twentyfour rats from the copied model rats and randomly dividing them into three groups:nephropathy group, low and high dose Ginsenoside Rgl treatment group. The general position was observated, weight was weighed, Twenty-four hours urine protein and renal function were measured the day before the rata were killed when the four weeks of treatments had been completed. Euzymelinked immunosorbent assay(ELISA) were performed to examine the protein expression levels of IL-4and TNF-a, respectively. The renal pathological and podocyte changes were evaluated.
Results:
1. The nephropathy group rats'general position was bad, there were no obvious differences during the four groups (P>0.05)
2. The nephropathy group's urine protein on the twenty eighth day increased Obviously compared with the normal and treatment group (P<0.01)
3. The nephropathy group's serum albumin decreased significantly,the cholesterol increased compared with the normal and treatment group (P<0.01).There was no obvious difference on albumin urea and creatinine during the four groups (P>0.05)
4. Compared with the normal group,The blood concentration of IL-4、TNF-a rats with nephropathy and Kidney-Qj Deficiency increased (P<0.01). The blood concentration of IL-4in the treatment group was inferior to the nephropathy group(P<0.01),but higher than the control group(P<0.05). The Ginsenoside Rgl treatment groups'blood concentration of TNF-a decreased significantly than nephropathy group (P<0.01), and had no difference with nomal group (P>0.05)
5.The electron microscope showed that the nephropathy group's foot process fusion was more obvious than treatment group's.
Conclusions:
1.Ginsenoside Rgl can improve the serum biochemical index, renal function and podocyte lesion.It can protect the nephridial tissue and repair kidney qi.
2. The mechanism of Ginsenoside Rgl protecting the nephridial tissue concludes decreasing blood conclusion of IL-4and TNF-a.
3.From the above conlusions it can be detected that the mechanism of Ginsenoside Rgl repairing kidney qi concludes regulating immune.
1.观察人参皂苷Rgl对肾病综合征肾气虚模型大鼠血生化、肾功能以及肾组织病理的影响以探讨其对肾是否有保护作用。
2.通过检测模型大鼠炎症因子白介素-4(IL-4)、肿瘤坏死因子－α (TNF－α)血清浓度来探索人参皂苷Rgl对肾具有保护作用的机制。
3.探讨人参补元气与调节炎症因子的关系。
方法：
40只雄性SD大鼠,正常组8只,其余采用盐酸多柔比星(5.0mg/kg)尾静脉注射,给药后采用慢性悬尾应激法强化肾气虚模型,造模后老鼠处于蜷缩状态,且疲乏无力,14天后,出现尿蛋白定量>100mg/24h提示模型复制成功,计入实验。随机分为模型组、人参皂苷Rgl低剂量组、人参皂苷Rgl高剂量组,每组各8只。观察一般状态,测体重,用代谢笼收集24h尿液,记录尿量行24h尿蛋白定量。检测肾功能。采用酶联免疫吸附法(ELISA)检测血清IL－4、TNF－α浓度。光镜及电镜观察肾组织的病理变化。
结果：
1.模型组大鼠一般状态差,各组大鼠体重增长无明显差异(P>0.05)。2.肾病大鼠模型组分组后第7天开始出现蛋白尿,14天后尿蛋白明显增加,28天达到高峰,与正常对照组相比,差异有显著性意义(p<0.01)。人参皂苷Rg1低剂量治疗组第7天尿蛋白比模型组稍减少(P<0.05),高剂量组减少明显(p<0.01),治疗组第14天,28天尿蛋白进一步减少,与模型组相比,差异有显著性意义(P<0.01)。3.模型组大鼠在分组28天后血清总蛋白(TP)、白蛋白(ALB)降低,胆固醇(CH)、甘油三酯(TG)增加,与正常组比较差异有显著统计学意义(P<0.01),人参皂苷组血清TP、ALB升高,CH、TG降低,与模型组比较差异有显著统计学意义(P<0.01)。各组血清尿素(BUN)、肌酐(Scr)无明显差异(P>0.05)。4.与正常组比较,模型组大鼠血清IL－4、TNF－α浓度均显著增加(P<0.01),人参皂苷Rg1组IL-4较模型组显著减少(P<0.01),但仍比正常组高(P<0.05),人参皂苷Rg1低剂量、高剂量组TNF－α均较模型组显著减少(P<0.01),与正常组比较无统计学意义。5.模型组大鼠足突融合,电镜显示比治疗组明显。
结论：
1.人参皂苷Rg1改善肾病综合征肾气虚模型大鼠血生化、肾功能以及肾足细胞病变,对肾组织有保护作用,根据其临床症状的改善表明能补肾气。
2.人参皂苷Rg1对肾组织具有肾保护作用的机制与降低血清炎症因子IL－4、TNF－α浓度有关。
3.依据人参的提取成分人参皂苷Rgl降低炎症因子浓度的同时改善肾气虚模型大鼠临床症状可以推测人参补元气的机制包括调节免疫。
Objectives:
1. To investigate the effects of Ginsenoside Rgl on serum biochemical index, renal function, and renal pathology in rats with nephropathy.
2.To detect the rats' serumlevel of IL-4and TNF-α and explor the ginsenoside Rgl's protective mechanism to kidney.
3.To study the correlation relationship between ginseng tonifying primordial Qi and regulating inflammatory factors.
Methods:
Random samplled eight rats for normal group from Forty male SD rats, the other were injected adriamycin(5mg/kg) in caudal vein once,and be hang the tail twice every day to reinforce the Kidney-Qj Deficiency model. The normal group were injected equivalent normal saline, After two weeks, the model rats curled up in a state and were lassitude,24h proteinuria was more than100mg,then the models were copied successfully. Random samplled twentyfour rats from the copied model rats and randomly dividing them into three groups:nephropathy group, low and high dose Ginsenoside Rgl treatment group. The general position was observated, weight was weighed, Twenty-four hours urine protein and renal function were measured the day before the rata were killed when the four weeks of treatments had been completed. Euzymelinked immunosorbent assay(ELISA) were performed to examine the protein expression levels of IL-4and TNF-a, respectively. The renal pathological and podocyte changes were evaluated.
Results:
1. The nephropathy group rats'general position was bad, there were no obvious differences during the four groups (P>0.05)
2. The nephropathy group's urine protein on the twenty eighth day increased Obviously compared with the normal and treatment group (P<0.01)
3. The nephropathy group's serum albumin decreased significantly,the cholesterol increased compared with the normal and treatment group (P<0.01).There was no obvious difference on albumin urea and creatinine during the four groups (P>0.05)
4. Compared with the normal group,The blood concentration of IL-4、TNF-a rats with nephropathy and Kidney-Qj Deficiency increased (P<0.01). The blood concentration of IL-4in the treatment group was inferior to the nephropathy group(P<0.01),but higher than the control group(P<0.05). The Ginsenoside Rgl treatment groups'blood concentration of TNF-a decreased significantly than nephropathy group (P<0.01), and had no difference with nomal group (P>0.05)
5.The electron microscope showed that the nephropathy group's foot process fusion was more obvious than treatment group's.
Conclusions:
1.Ginsenoside Rgl can improve the serum biochemical index, renal function and podocyte lesion.It can protect the nephridial tissue and repair kidney qi.
2. The mechanism of Ginsenoside Rgl protecting the nephridial tissue concludes decreasing blood conclusion of IL-4and TNF-a.
3.From the above conlusions it can be detected that the mechanism of Ginsenoside Rgl repairing kidney qi concludes regulating immune.
引文
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[1]薛辛东.儿科学.第二版[M].北京：人民卫生出版社,2010.330-331
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[22]Lee EJ,Ko E,Lee J,et al.Ginsenoside Rgl enhances CD4(+)T-cell activities and modulates Th1/Th2 differentiation[J].Int Immunophamacol 2004,4(2):235-244
[23]Lee JH,Han Y.Ginsenoside Rgl helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4(+) T cell[J].Int Immunopharmacol,2006,6(9):1424-1430
[24]Lizakowski S,Zdrojewski Z,Jagodzinski P,et al. Plasma tissue factor and tissue factor pathway inhibitor in patients with primary glomerulonephritis. Scand J Urol Nephrol.2007,41(3):237-242
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[30]Leung KW, Pon YL, Wong RN,et al:Ginsenoside-Rgl induces vascular endothelial growth factor expression through glucocorticoid receptor-related phosphatidylinositol 3-kinse/Akt and β-catenin/TCF-dependent pathway in human endothelial cells[J]. J Biol Chem 2006,281(47):36280-36288.
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