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牛膝白芍颗粒配伍对肝阳上亢型高血压肾损伤的保护作用

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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.
Protective effects of the particle combination of Hyssop and White Peony on the kidney of mice with hypertensive nephropathy on the liver yang
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.

HyssopWhite Peonyhypertensive hypertension on the liver yangkidney damageoxidative stress

陆彭、康达、刘洺岐、伍鼎骁、张艳艳、颜沛梅、何雨慧、任珊、李雪、林岩

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齐齐哈尔医学院基础医学院,黑龙江 齐齐哈尔 161006

齐齐哈尔医学院黑龙江省药食同源资源与代谢性疾病防治重点实验室,黑龙江 齐齐哈尔 161006

牛膝 白芍 肝阳上亢型高血压 肾损伤 氧化应激

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(22)