[关键词]
[摘要]
研究了人参加工品“鲜人参膏”(Fresh Ginseng Paste,FGP)对顺铂(Cisplatin,CDDP)致急性肾损伤小鼠的保护作用,并探讨其潜在的作用机制。检测小鼠血清中尿素氮(BUN)和肌酐(CRE)水平,评价肾功能变化;检测肾组织中超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)活性及丙二醛(MDA)含量,评价氧化应激水平;并通过H&E、TUNEL、Hoechst 33258和免疫组织化学染色法观察肾组织病理学变化,同时采用蛋白质印迹法(Western blot)分析细胞凋亡情况。结果显示:与正常组比,CDDP组血清CRE含量增加了96.97 μmol/L,BUN含量增加了16.71 mmol/L,肾组织中MDA升高了1.29 μmol/mg,GSH含量降低了5.74 μmol/g,SOD活性降低了49.94 U/mg protein(p<0.05)。与CDDP组比,FGP各剂量组均可降低血清CRE、BUN及肾组织中的MDA含量,增强肾脏GSH、SOD活性(p<0.05);此外,肾组织糖原沉积明显减少,肾小管上皮细胞凋亡明显被抑制(p<0.05),同时改善了肾组织坏死和凋亡程度。Western blot分析表明,FGP能够明显抑制Bax和cleaved caspase-3等凋亡蛋白的过表达和降低Bcl-2的蛋白水平。FGP对CDDP诱导小鼠肾损伤具有明显的保护作用,其机制可能与改善氧化应激及抗细胞凋亡有关。
[Key word]
[Abstract]
The protective effect of fresh Ginseng Paste (FGP) on cisplatin (CDDP)-induced acute kidney injury in mice was studied here and its potential mechanism was explored. The renal function was evaluated by determining the serum levels of urea nitrogen (BUN) and creatinine (CRE) in mice. The oxidative stress level was evaluated by the detection of superoxide dismutase (SOD) and reduced glutathione (GSH) activity in kidney tissues and malondialdehyde (MDA) content. The pathological changes of renal tissues were observed by using H&E, TUNEL, Hoechst 33258 and immunohistochemical staining, and the apoptosis was analyzed by western blot analysis. The results clearly showed that compared with the normal group, the serum CRE and BUN in CDDP group increased by 96.97 μmol/L and 16.71 mmol/L, respectively. The MDA content in the renal tissues increased by 1.29 μmol/mg, and the GSH content decreased by 5.74 μmol/g, the activity of SOD was reduced by 49.94 U/mg (p<0.05). Compared with the CDDP group, FGP inhibited the overproduction of MDA, the increases of CRE and BUN. Moreover, FGP treatment increased the renal levels of GSH and SOD (p<0.05). FGP decreased the tissue glycogen deposition and the apoptosis of renal tubular epithelial cells (p<0.05). Western blot analysis indicated that FGP could significantly inhibit the overexpression of Bax and cleaved caspase-3 and reduce the protein expression level of Bcl-2. In summary, FGP exerted a protective effect on CDDP-induced renal injury in mice, and its mechanism may be related to the improvement of oxidative stress and anti-apoptosis.
[中图分类号]
[基金项目]
吉林省科技发展计划项目资助(20191102051YY)