金丝桃苷调控胰岛素受体底物1/磷脂酰肌醇3-激酶/蛋白激酶B信号通路对糖尿病肾病大鼠肾组织损伤的保护作用  

Protective effect of hyperoside on renal tissue damage in rats with diabetic nephropathy by regulating the insulin receptor substrate 1/phosphatidylinositol 3-kinase/protein kinase B signaling pathway

作　　者：张元丽 王素利 张宇 朱德礼 刘晏汝 刘英莲[3] ZHANG Yuan-li;WANG Su-li;ZHANG Yu;ZHU De-li;LIU Yan-ru;LIU Ying-lian(Department of Nephropathy and Endocrinology,Sanya Traditional Chinese Medicine Hospital,Sanya 572000,Hainan Province,China;Department of Geriatric Disease and Nephropathy,The First Affilliated Hospital to Changchun University of Chinese Medicine,Changchun 130021,Jilin Province,China;College of Traditional Chinese Medicine,Hainan Medical University,Haikou 571199,Hainan Province,China)

机构地区：[1]三亚市中医院肾病内分泌科,海南三亚572000 [2]长春中医药大学附属医院老年病肾病科,吉林长春130021 [3]海南医学院中医学院,海南海口571199

出　　处：《中国临床药理学杂志》2023年第2期241-245,共5页The Chinese Journal of Clinical Pharmacology

基　　金：吉林省卫生厅健康发展计划基金资助项目(2019Q698)。

摘　　要：目的 探索金丝桃苷对糖尿病肾病(DN)大鼠胰岛素受体底物1(IRS-1)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的影响,及其对肾组织损伤的保护作用。方法 用腹腔注射链脲佐菌素的方法建立DN大鼠模型,并随机分为模型组、对照组和低、中、高剂量实验组,每组12只;另取12只SD大鼠设为假手术组。低、中、高剂量实验组按10 mL·kg^(-1)的剂量分别灌胃给予12.5,25.0和50.0 g·kg^(-1)金丝桃苷,qd;对照组按10 mL·kg^(-1)的剂量灌胃给予7.0 mg·mL^(-1)二甲双胍溶液,qd;假手术组与模型组大鼠均灌胃给予等量0.9%NaCl。6组大鼠连续给药21 d。检测大鼠血糖、尿微量白蛋白(UMA)水平,用蛋白质印迹法检测肾组织IRS-1/PI3K/Akt通路蛋白的表达水平。结果 低、高剂量实验组和对照组、模型组、假手术组的血糖分别为(21.04±2.65),(5.86±0.82),(5.72±0.93),(28.23±3.17)和(5.12±0.73)mmol·L^(-1),UMA分别为(100.76±20.49),(10.02±1.71),(9.97±1.78),(145.82±32.07)和(8.26±1.13)mmol·L^(-1),p-PI3K/PI3K值分别为0.32±0.05,0.97±0.17,0.96±0.16,0.10±0.02和0.99±0.19,p-Akt/Akt值分别为0.27±0.04,0.84±0.14,0.83±0.15,0.07±0.02和0.87±0.13,p-IRS-1/IRS-1值分别为0.76±0.15,0.18±0.05,0.17±0.04,1.02±0.23和0.12±0.02。低、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论 金丝桃苷可降低IRS-1磷酸化水平,激活PI3K/Akt通路,减轻DN大鼠肾组织病理损伤。Objective To explore the effect of hyperoside on insulin receptor substrate 1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in diabetic nephropathy(DN) rats and its protective effect on rats with renal tissue damage.Methods The DN rat model was established by intraperitoneal injection of streptozotocin,and the rats were randomly divided into model group,control group and experimental-L,-M,-H groups,with 12 rats in each group.Another 12 SD rats were regarded as the sham-operation group.The experimental-L,-M,-H groups were given 12.5,25.0and 50.0 g·kg^(-1)of hyperoside by gavage at a dose of 10 m L·kg^(-1),respectively,qd.The control group was given7.0 mg·m L-1metformin solution by gavage at a dose of 10 m L·kg^(-1),qd.The sham-operation group and the model group were given the same amount of 0.9%NaCl by gavage.Rats in the six groups were continuously administered for21 days.The levels of blood glucose and urine microalbumin (UMA) were detected in rats.The expression levels of IRS-1/PI3K/Akt pathway proteins in kidney tissue were detected by Western blot.Results The blood glucose levels in the experimental-L,-H groups,control group,model group and sham-operation group were (21.04±2.65),(5.86±0.82),(5.72±0.93),(28.23±3.17) and (5.12±0.73) mmol·L^(-1);the UMA were(100.76±20.49),(10.02±1.71),(9.97±1.78),(145.82±32.07) and (8.26±1.13) mmol·L^(-1);the p-PI3K/PI3K values were 0.32±0.05,0.97±0.17,0.96±0.16,0.10±0.02 and 0.99±0.19;the p-Akt/Akt values were 0.27±0.04,0.84±0.14,0.83±0.15,0.07±0.02 and 0.87±0.13;the p-IRS-1/IRS-1 values were 0.76±0.15,0.18±0.05,0.17±0.04,1.02±0.23 and 0.12±0.02,respectively.Compared with the model group,the above indexes in the experimental-L,-H groups were significantly different (all P<0.05).Conclusion Hyperoside can reduce the phosphorylation level of IRS-1,activate the PI3K/Akt pathway,and reduce the pathological damage of renal tissue in DN rats.

关 键 词：金丝桃苷 糖尿病肾病 胰岛素受体底物1/磷脂酰肌醇3-激酶/蛋白激酶B信号通路 肾组织损伤 

分 类 号：R28[医药卫生—中药学]