摘要
目的研究白芍总苷对糖尿病大鼠肾损伤的保护性作用及机制。方法用高糖高脂饲养及腹腔注射链佐菌素的方法构建糖尿病大鼠模型,将建模成功的大鼠随机分为模型组(n=10)和低(n=10)、高剂量实验组(n=10),另选10只正常大鼠,腹腔注射10 mL·kg^(-1)枸橼酸钠缓冲液作为对照组。低、高剂量实验组分别给予80 mg·kg^(-1)·d^(-1)和160 mg·kg^(-1)·d^(-1)白芍总苷,灌胃,对照组和模型组给予25 mL·kg^(-1)1%羧甲基纤维素钠溶液,灌胃,连续干预10 d。测量大鼠体重(BW),用全自动生化分析仪测量大鼠空腹血糖(FBG)、空腹胰岛素(FINS)、血清肌酸酐(Scr)和24 h尿微量白蛋白(mALB)水平;取各组大鼠肾上皮细胞,用细胞计数试剂盒-8(CCK-8)法测定细胞存活率;用原位末端转移酶标记技术(TUNEL)法检测细胞凋亡率;用蛋白质印迹(Western blot)法检测B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、微管相关蛋白1轻链3β(LC3B)、硫氧还蛋白相互作用蛋白(Thioredoxin-interacting protein,TXNIP)的表达。结果对照组、模型组和低、高剂量实验组大鼠空腹体重分别为(379.32±60.36),(549.96±70.96),(496.12±74.07)和(480.56±61.73)g;FBG分别为(5.42±0.57),(19.30±1.84),(14.85±1.68)和(13.72±1.08)mmol·L^(-1);FINS分别为(18.66±1.52),(29.48±4.10),(26.21±3.92)和(21.26±3.65)mU·L^(-1);Scr分别为(25.75±3.63),(39.28±4.99),(30.70±3.43),(23.94±3.22)μmol·L^(-1);mALB分别为(89.71±7.98),(337.78±35.64),(205.01±25.11)和(173.37±26.90)μg;细胞存活率分别为(100.00±0.00)%,(53.64±4.23)%,(62.26±5.05)%,(69.21±3.75)%;细胞凋亡率分别为(8.55±0.92)%,(37.14±2.88)%,(33.33±4.03)%,(26.79±2.74)%。以上指标,模型组与对照组相比较,低、高剂量实验组与模型组相比较,差异均有统计学意义(均P<0.05)。结论白芍总苷能显著抑制肾小管上皮细胞凋亡,促进细胞增殖并诱导自噬减轻糖尿病大鼠肾损伤,其作用机制可能与下调TXNIP表达有关。
Objective To explore the protective effect and mechanism of total peony glycosides on renal injury in diabetic rats.Methods The rats were randomly divided into model group(n=10),low dose experimental group(n=10)and high dose experimental group(n=10),and 10 normal rats were selected and injected intraperitoneally with 10 mL·kg^(-1) sodium citrate buffer as control group.The low and high dose experimental groups were given 80 and 160 mg·kg^(-1)·d^(-1) total peony glycosides by gavage,control and model groups were given 25 mL·kg^(-1)1%sodium carboxymethylcellulose solution for 10 d of continuous intervention by gavage.Body weight(BW)was measured and fasting blood glucose(FBG),fasting insulin(FINS),serum creatinine(Scr)and 24 h urinary microalbumin(mALB)levels were measured in rats by fully automated biochemical analyzer.The cell survival rate was measured by the cell counting kit-8(CCK-8)method;the apoptosis rate was measured by in situ terminal transferase labeling technique(TUNEL);the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),microtubule-associated protein 1 light chain 3β(LC3B)and thioredoxin-interacting protein(TXNIP)were measured by Western blot.Results The fasting BW of rats in control group,model group and low,high dose experimental group were(379.32±60.36),(549.96±70.96),(496.12±74.07)and(480.56±61.73)g;FBG were(5.42±0.57),(19.30±1.84),(14.85±1.68)and(13.72±1.08)mmol·L^(-1);FINS were(18.66±1.52),(29.48±4.10),(26.21±3.92)and(21.26±3.65)mU·L^(-1);Scr were(25.75±3.63),(39.28±4.99),(30.70±3.43),(23.94±3.22)μmol·L^(-1);mALB were(89.71±7.98),(337.78±35.64),(205.01±25.11)and(173.37±26.90)μg;the cell survival rates were(100.00±0.00)%,(53.64±4.23)%,(62.26±5.05)%,(69.21±3.75)%;the cell apoptosis rates were(8.55±0.92)%,(37.14±2.88)%,(33.33±4.03)%,(26.79±2.74)%.For the above data,the differences between model group and control group,between low,high dose experimental groups and model group were statistically significant(all P<0.05).Conclusion Total peony
作者
崔丽
刘桂凌
史光彩
苏超
CUI Li;LIU Gui-ling;SHI Guang-cai;SU Chao(Department of Nephrology,Second Affiliated Hospital of Anhui Medical University,Hefei 230601,Anhui Province,China;Department of Nephrology,Hefei Fifth People’s Hospital,Hefei 230011,Anhui Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第22期3107-3110,共4页
The Chinese Journal of Clinical Pharmacology