硝苯地平对慢性铁过负荷大鼠铁沉积和营养代谢的影响

目的观察硝苯地平对慢性铁过负荷大鼠肝、肾和脾组织铁沉积与营养代谢的影响,探讨硝苯地平治疗铁过负荷等代谢疾病的可能性。方法雄性SD大鼠连续8周喂饲铁含量为3.5 g.kg-1的高铁饲料,制备慢性铁过负荷动物模型。8周后,模型大鼠ip给予硝苯地平1,3和5 mg.kg-1,连续7 d。组织学染色观察肝、肾和脾组织铁沉积,用试剂盒分别测定血脂、脂质过氧化及抗氧化指标,同时测定血清铁蛋白(SF)和总铁结合力(TIBC);用全自动生化分析仪或荧光分光光度计检测血清中营养元素铁、钙、锌和硒的含量。结果与正常对照组比较,慢性铁过负荷模型组大鼠肝、肾和脾组织中铁沉积明显;与模型组比较,硝苯地平5 mg.kg-1组组织中铁沉积明显降低(P<0.05,P<0.01)。与正常对照组比较,模型组血清甘油三酯(TG)含量由1.25±0.21升高到(1.86±0.75)mmol.L-1,总胆固醇(TC)由1.52±0.17升高到(1.91±0.34)mmol.L-1,丙二醛(MDA)由11.2±2.8升高到(15.3±3.6)μmol.L-1,谷胱甘肽过氧化物酶(GSH-Px)活性由204±52升高到(286±75)kU.L-1(P<0.05),高密度脂蛋白(HDL)、低密度脂蛋白(LDL)含量和超氧化物歧化酶(SOD)活性无明显变化;与模型组比较,硝苯地平5 mg.kg-1组TC降低到(1.65±0.36)mmol.L-1,LDL由1.14±0.15降低到(0.86±0.16)mmol.L-1,MDA含量降低到(11.9±3.5)μmol.L-1(P<0.05),TG,HDL,SOD和GSH-Px无明显变化;硝苯地平1和3 mg.kg-1对上述指标无明显影响。与正常对照组比较,模型组血清中铁含量由1.21±0.11升高到(1.57±0.25)mg.L-1,SF由232±17升高到(348±46)mg.L-1,锌、硒和钙含量分别由1.8±0.6,0.096±0.018和(120±26)mg.L-1降低到1.4±0.4,0.072±0.012和(77±15)mg.L-1(P<0.05,P<0.01),TIBC无明显变化;与模型组比较,硝苯地平5 mg.kg-1组血清铁含量降低到(1.32±0.14)mg.L-1,硒含量升高到(0.087±0.017)mg.L-1,钙含量升高到(97±16)mg.L-1(P<0.05),对SF,TIBC和锌含量无明显影响;硝苯地平1和3 mg.kg-1对上述指标无明显影响。结论硝苯地平能减少铁沉积,改善慢性铁过负荷大鼠的营养代谢,对铁过负荷等代谢疾病可能具有一定的治疗作用。

Effects of nifedipine on iron deposits and nutritional metabolism in chronic iron-overload rats

OBJECTIVE To observe effects of nifedipine on iron deposits in livers, kindeys and spleens, and nutritional metabolism of chronic iron overload rats and explore probability to cure iron overload in human. METHODS SD male rats were administrated iron 3.5 g·kg^-1 for 8 weeks. All chronic iron overload model groups were ip given nifedipine 1, 3 and 5 mg·kg^-1 for 7 d continuously. Rats were sacrificed after the last injection, the iron deposits in livers, kindeys and spleens were observed by histological staining. Blood lipid levels, lipid peroxidation indexes and activities of antioxidant enzymes were determined by assay kits, and contents of serum ferritin (SF) and total iron- binding capacity (TIBC) were determined. The contents of serum Fe, Zn, Se and Ca were also determined used by automatic chemistry analyzer or fluorescence spectrophotometer. RESULTS Compared with normal control group, iron deposits in livers, kindeys and spleens increase significantly in chronic iron overload model group, but decreased significantly in nifedipine 5 mg·kg^-1 group(P<0.05, P<0.01). Compared with normal control group, the levels of TG increase from 1.25±0.21 to (1.86±0.75)mmol·L^-1, TC from 1.52±0.17 to (1.91±0.34)mmol·L^-1, MDA from 11.2±2.8 to (15.3±3.6)μmol·L^-1, the activity of glutathione peroxidase (GSH-Px) from 204±52 to (286±75)kU·L^-1, but the levels of HDL, LDL and the activity of SOD have no significant change in model group. After 7 d treatment, compared to model group, levels of TC decrease to (1.65±0.36)mmol·L^-1, levels of LDL decrease from 1.14±0.15 to (0.86±0.16)mmol·L^-1, contents of MDA decrease to (11.9±3.5)μmol·L^-1, but contents of serum TG and HDL, SOD and GPx activities have no significant change in nifedipine 5 mg·kg^-1 group. In nifedipine 1 and 3 mg·kg^-1 groups, the above indexes have no significant changes. Compared with normal control group, serum contents increase from 1.21±0.11 to (1.57±0.25)mg·L^-1, ferritin from 231.87±17.12 to (348.42±46.22)mg·L^-1, the contents of serum Zn, Se, and Ca decrease from 1.8±0.6, 0.096±0.018, 120±26 to 1.4±0.4, 0.072±0.012, (77±15)mg·L^-1, respectively, but TIBC contents has no significant changes in model group. After 7 d treatment, compared with model group, serum Fe contents decrease to (1.32±0.14)mg·L^-1, serum Se and Ca increase to 0.087±0.017 and (97±16)mg·L^-1, respectively, but serum ferritin, TIBC and Zn contents have no significant change in model group. In nifedipine 1 and 3 mg·kg^-1 groups, above indexes have no significant changes. CONCLUSION Nifedipine can decrease iron deposits in livers, kindeys and spleens, and improve nutritional metabolism of chronic iron overload rats. It will be a better way to cure the chronic iron overload in human.