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Abstract：
BACKGROUND: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis.
METHODS: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined.
RESULTS: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized.
CONCLUSIONS: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.
METHODS: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined.
RESULTS: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized.
CONCLUSIONS: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.
摘要：
背景：已知肾功能下降与生物衰老有关，以慢性炎症和肾间质纤维化为主要病理特征。在以往的研究中,我们报道了竹节参总皂苷（SPJs）可以有效地保护急性心肌缺血。我们提出SPJs可能对衰老相关的肾间质纤维化有类似的保护作用。因此，在本研究中，我们评估了SPJs对肾脏纤维化的总体影响.
方法：Sprague-Dawley(SD)衰老大鼠从18个月大开始灌胃给予SPJs，在10毫克/千克/天和60毫克/千克/天，到24个月大。实验之后,形态的变化，检测其肾脏的功能和纤维化。血清尿酸（UA）水平，用ELISA试剂盒检测β2-微球蛋白(β2-MG)和胱抑素C(CysC)。细胞外基质（ECM）的水平，基质金属蛋白酶（MMPs），金属蛋白酶组织抑制剂（TIMPs），检测炎症因子和氧化应激参数的变化。
结果：SPJs治疗后，SD大鼠肾脏组织病理学改变明显,肾纤维化程度降低,肾功能增强;与3个月组比较,血清UA水平，24个月组CysC和β2-MG明显升高(p<0.05)。与24个月组相比，血清UA水平，SPJ-H组CysC和β2-MG明显下降。而ECM减少，MMP-2和MMP-9的水平增加，TIMP-1，TIMP-2和转化生长因子-β1（TGF-β1）/Smad信号水平降低；磷酸化核因子κB（NF-κB）的表达水平下调，炎症因子降低；同时，核因子红系2相关因子2-抗氧化反应元件(Nrf2-ARE)信号的表达增强。
结论：这些结果表明，SPJs治疗可以通过抑制TGF-β1/Smad改善年龄相关性肾纤维化，NFκB信号通路和激活Nrf2-ARE信号通路和SPJs可能是一种潜在有价值的抗肾纤维化药物。
方法：Sprague-Dawley(SD)衰老大鼠从18个月大开始灌胃给予SPJs，在10毫克/千克/天和60毫克/千克/天，到24个月大。实验之后,形态的变化，检测其肾脏的功能和纤维化。血清尿酸（UA）水平，用ELISA试剂盒检测β2-微球蛋白(β2-MG)和胱抑素C(CysC)。细胞外基质（ECM）的水平，基质金属蛋白酶（MMPs），金属蛋白酶组织抑制剂（TIMPs），检测炎症因子和氧化应激参数的变化。
结果：SPJs治疗后，SD大鼠肾脏组织病理学改变明显,肾纤维化程度降低,肾功能增强;与3个月组比较,血清UA水平，24个月组CysC和β2-MG明显升高(p<0.05)。与24个月组相比，血清UA水平，SPJ-H组CysC和β2-MG明显下降。而ECM减少，MMP-2和MMP-9的水平增加，TIMP-1，TIMP-2和转化生长因子-β1（TGF-β1）/Smad信号水平降低；磷酸化核因子κB（NF-κB）的表达水平下调，炎症因子降低；同时，核因子红系2相关因子2-抗氧化反应元件(Nrf2-ARE)信号的表达增强。
结论：这些结果表明，SPJs治疗可以通过抑制TGF-β1/Smad改善年龄相关性肾纤维化，NFκB信号通路和激活Nrf2-ARE信号通路和SPJs可能是一种潜在有价值的抗肾纤维化药物。
