首页|当归红芪超滤膜提取物改善糖尿病肾病大鼠肾损伤的作用

当归红芪超滤膜提取物改善糖尿病肾病大鼠肾损伤的作用

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目的 探讨当归红芪超滤膜提取物改善糖尿病肾病(DKD)大鼠肾损伤可能的作用机制.方法 用腹腔注射链脲佐菌素制备糖尿病模型,再用高糖高脂饲料喂养构建DKD模型.将造模成功的DKD大鼠分为模型组、阳性对照组和低、中、高剂量实验组,每组8只;另取8只Wistar大鼠作空白组.低、中、高剂量实验组分别灌胃给予1.5、3.0和6.0 g·kg-1当归红芪超滤膜提取物溶液;阳性对照组灌胃给予1.75×10-3g·kg-1厄贝沙坦悬浊液;空白组和模型组均灌胃给予等体积纯净水.6组大鼠每天给药1次,连续给药12周.用考马斯亮蓝法测定24 h尿总蛋白(24h-UTP),用蛋白质印迹法检测大鼠肾组织核因子红系2相关因子2(Nrf2)、血红素氧合酶1(HO-1)及长链脂酰辅酶A合成酶4(ACSL4)蛋白的表达水平.结果 中、高剂量实验组和阳性对照组、模型组、空白组的 24 h-UTP 分别为(47.70±3.85)、(43.57±6.38)、(36.80±6.52)、(64.34±13.38)和(7.58±3.71)mg,Nrf2蛋白相对表达水平分别为0.86±0.08、0.75±0.06、0.64±0.08、1.09±0.06 和0.60±0.07,HO-1 蛋白相对表达水平分别为 0.77±0.04、0.63±0.07、0.47±0.05、1.04±0.06 和0.34±0.07,ACSL4 蛋白相对表达水平分别为 0.62±0.07、0.55±0.07、0.46±0.06、1.08±0.07和0.30±0.01.中、高剂量实验组和阳性对照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(P<0.05,P<0.01).结论 当归红芪超滤膜提取物可以改善DKD大鼠肾损伤,其机制可能与抑制Nrf2/HO-1通路过度激活导致的铁死亡有关.
Effects of ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix improves the kidney injury in diabetic kidney disease rats
Objective To explore the improve mechanism of ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix on kidney injury in diabetic kidney disease(DKD)rats.Methods The diabetes model was prepared by intraperitoneal injection of streptozotocin,and then fed with high sugar and high fat diet.The rats with successful DKD were randomly divided into model group,positive control group and experimental-L,-M,-H groups with 8 cases per group.Additionally,selected 8 Wistar rats as the blank group.The experimental-L,-M,-H groups were given 1.5,3.0 and 6.0 g·kg-1 ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix by gavage,respectively.The positive control group was given 1.75 × 10-3 g·kg-1irbesartan suspension by gavage.The blank and model groups were given equal volume of pure water by gavage.Six groups were administrated once a day for 12 consecutive weeks.The 24 h-urinary total protein were detected by coomassie brilliant blue method.The protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and andacyl-CoA synthetase long chain family member 4(ACSL4)in kidney tissue were detected by Western blot.Results The 24 h-UTP in the experimental-M,-H groups,positive control group,model group and blank group were(47.70±3.85),(43.57±6.38),(36.80±6.52),(64.34±13.38)and(7.58±3.71)mg;the relative expression levels of Nrf2 protein were 0.86±0.08,0.75±0.06,0.64±0.08,1.09±0.06 and 0.60±0.07;the relative expression levels of HO-1 protein were 0.77±0.04,0.63±0.07,0.47±0.05,1.04±0.06 and 0.34±0.07;the relative expression levels of ACSL4 protein were 0.62±0.07,0.55±0.07,0.46±0.06,1.08±0.07 and 0.30±0.01,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups and positive control group were significantly different(P<0.05,P<0.01).Conclusion Ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix can improve the damage of kidney tissue in DKD rats,and the mechanism may be related to ferroptosis caused by excessive activation of Nrf2/HO-1 signaling pathway.

ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radixdiabetes kidney diseaseferroptosisnuclear factor erythroid2-related factor 2/heme oxygenase-1 signaling pathway

徐庆全、张小琳、高婷、李荣科、张磊、万生芳

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甘肃中医药大学 基础医学院,甘肃 兰州 730000

当归红芪超滤膜提取物 糖尿病肾病 铁死亡 核因子红系2相关因子2/红素氧合酶1信号通路

国家自然科学基金资助项目

82060914

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(20)