【摘要】 目的：探索慈姑多糖（SSP）是否通过激活核转录因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路对6种重金属联用所致小鼠肾损伤发挥预防保护作用。方法：根据北京市售大米Cd、Cr(VI)、Pb、Cu、Zn、Mn 6种重金属膳食摄入比例，构建重金属混合染毒液诱导小鼠肾损伤体内模型。40只雄性昆明小鼠随机分为对照组，模型组，阳性对照组（谷胱甘肽0.9 g/kg）和SSP低、高剂量组（0.2、0.8 g/kg），每组8只。灌胃干预30 d，每5天称量小鼠体质量。HE染色观察小鼠肾脏损伤情况；计算肾脏指数；全自动生化分析仪检测小鼠血清尿素氮（BUN）和肌酐（Scr）含量；电感耦合等离子体质谱仪检测肾脏中6种重金属的含量。试剂盒检测丙二醛（MDA）、谷胱甘肽（GSH）含量和过氧化氢酶（CAT）活性；Western Blot测定Nrf2、HO-1、B淋巴细胞瘤-2(Bcl-2)、Bcl-2关联X蛋白（Bax）的表达。结果：HE染色观察提示，与模型组比较，SSP各剂量组肾脏中炎性渗出显著减轻，肾小管空泡变性明显改善，其中高剂量组的改善效果尤为突出。与模型组比较，SSP高剂量组BUN、Scr、MDA以及肾脏重金属（Zn、Cr、Mn、Pb、Cd）含量显著降低（P<0.05,P<0.01）,GSH含量和CAT活性显著升高（P<0.01）,Nrf2和Bcl-2蛋白表达显著升高（P<0.01）,HO-1和Bax蛋白表达显著降低（P<0.01）。结论：SSP或可通过调节Nrf2/HO-1信号通路、缓解氧化损伤所致细胞凋亡来改善6种重金属联用导致的肾损伤。更多还原

【Abstract】 Objective: To explore whether Sagittaria sagittifolia polysaccharide(SSP) plays a protective role in renal injury induced by the mixture of six heavy metals in mice by activating Nrf2/HO-1 signaling pathway. Methods: Choosing the rice sold in Beijing, China and referring to its proportion of heavy metal content to prepare joint mixture of Cd, Cr(VI), Pb, Cu, Zn and Mn, and the in vivo model of kidney injury induced by the mixture of heavy metals was established. Forty male Kunming mice were randomly divided into: control group, model group, glutathione positive control group(0.9 g/kg), SSP low-dose and highdose groups(0.2, 0.8 g/kg), with 8 mice in each group. The mice were weighed every 5 days and gavage intervention lasted for 30 days. HE staining was applied to observe the pathological changes of kidney injury in mice. The kidney index was calculated.Blood urea nitrogen(BUN) and serum creatinine(Scr) levels were measured by automatic biochemical analyzer. Inductively coupled plasma mass spectrometer(ICP/MS) method was applied to detect the contents of six heavy metals in the kidney.The levels of malondialdehyde(MDA), glutathione(GSH) and activity of catalase(CAT) were detected by using assay kits.The expression of Nrf2, HO-1, Bcl-2 and Bax were detected by Western Blot. Results: HE staining suggested that compared with the model group, the inflammatory exudation and vacuolar degeneration of renal tubules were significantly improved in the SSP treatment groups, and the effect was more obvious in the high-dose group. Compared with model group, the contents of BUN,Scr, MDA and heavy metals(Zn, Cr, Mn, Pb, Cd) in kidney of SSP high-dose group significantly decreased(P<0.05, P<0.01), the GSH level and CAT activity significantly increased(P<0.01), the protein expressions of Nrf2 and Bcl-2 significantly increased(P<0.01), and the protein expressions of HO-1 and Bax significantly decreased(P<0.01). Conclusion: SSP can effectively improve renal injury induced by the six heavy metals mixture, and its underlying mechanism may be related to the regulation of Nrf2/HO-1signaling pathway to alleviate oxidative damage and apoptosis.更多还原