摘要
目的 观察牛膝白芍联合用药对N-硝基-L-精氨酸甲酯(L-NAME)和附子联合诱导的高血压肾损伤小鼠核因子E2相关因子-2(Nrf2)/血红素加氧酶-1(HO-1)信号通路的影响,及其治疗机制.方法 将80只KM小鼠随机分为空白组、模型组和实验A、B、C、D、E、F组,每组10只.除空白组外,其余7组均灌胃给予附子汤+L-NAME制备高血压肾损伤模型.实验A、B、C、D、E、F组分别灌胃给予6.83 g·kg-1·d-1不同比例配伍的牛膝-白芍溶液,分别为5∶0、4∶1、3∶2、2∶3、1∶4、0∶5;空白组和模型组均灌胃给予等体积蒸馏水.8组小鼠均干预6周.比较各组小鼠的血压变化,用试剂盒检测血清中尿素氮(BUN)和肾组织中超氧化物歧化酶(SOD)的水平,用免疫组化法检测小鼠肾组织中Nrf2和HO-1的表达情况.结果 空白组、模型组和实验C、D组的收缩压分别为(99.56±4.13)、(140.11±7.33)、(106.23±8.41)和(105.97±6.43)mmHg,血尿素氮含量分别为(172.00±15.90)、(352.64±17.23)、(201.76±12.14)和(192.72±12.77)μg·mL-1,SOD 活性分别为(232.14±8.58)、(165.44±6.17)、(205.06±5.34)和(182.94±9.91)U·mL-1,Nrf2蛋白表达水平(光密度值)分别为2.06±0.14、2.25±0.22、2.63±0.22和2.83±0.21,HO-1蛋白表达水平(光密度值)分别为2.18±0.12、2.25±0.10、2.64±0.16和2.65±0.28.实验C、D组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P＜0.01).结论 牛膝白芍联合用药能够通过激活Nrt2/HO-1通路,增强L-NAME和附子联合诱导的高血压肾损伤小鼠机体抗氧化应激的能力,从而发挥其对肾的保护作用.
Abstract
Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)µg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)µg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.
维普
万方数据